Biodegradable plates and screws in oral and maxillofacial surgery Buijs, Gerrit Jacob

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1 University of Groningen Biodegradable plates and screws in oral and maxillofacial surgery Buijs, Gerrit Jacob IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2011 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Buijs, G. J. (2011). Biodegradable plates and screws in oral and maxillofacial surgery Groningen: s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 BIODEGRADABLE PLATES AND SCREWS IN ORAL AND MAXILLOFACIAL SURGERY Thesis Jappe Buijs

3 The research presented in this thesis was performed at the Department of Oral and Maxillofacial Surgery, University Medical Centre Groningen, The Netherlands. RIJKSUNIVERSITEIT GRONINGEN This research was financially supported by: Board of the UMCG, Straumann, Camlog, Nobel Biocare, BioComp, Inion Ltd., ConMed Linvatec Biomaterials Ltd., KLS Martin, Synthes, Dental Union, Henry Schein, NVGPT, Fred Ribôt tandtechniek, Examvision, BIODEGRADABLE PLATES AND SCREWS IN ORAL AND MAXILLOFACIAL SURGERY Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. E. Sterken, in het openbaar te verdedigen op woensdag 14 september 2011 om uur door Gerrit Jacob Buijs, 2011 All rights reserved. No parts of this publication may be transmitted, in any form or by any means, without permission of the author. Gerrit Jacob Buijs geboren op 18 november 1980 te Purmerend Bookdesign: Sgaar Groningen Printed by: Drukkerij van der Eems Heerenveen ISBN:

4 Promotores: Prof. dr. R.R.M. Bos Prof. dr. B. Stegenga Prof. dr. G.J. Verkerke Paranimfen: N.B. van Bakelen H.J.W.E. de Lange Copromotor: Dr. J. Jansma Beoordelingscommissie: Prof. dr. dr. K.L. Gerlach Prof. dr. J. de Lange Prof. dr. D.B. Tuinzing

5 CONTENTS Chapter 1 09 General introduction Chapter 2 17 Efficacy and Safety of Biodegradable Osteofixation Devices in Oral and Maxillofacial Surgery: a Systematic Review G.J. Buijs, B. Stegenga, R.R.M. Bos Published in: J Dent Res Nov;85(11): Chapter Torsion Strength of Biodegradable and Titanium Screw Systems: a Comparison G.J. Buijs, E.B. van der Houwen, B. Stegenga, R.R.M. Bos, G.J. Verkerke Published in: J Oral Maxillofac Surg Nov;65(11): Chapter 6 99 Reference List Chapter Summary Chapter Dutch summary Dankwoord 127 Chapter Mechanical Strength and Stiffness of Biodegradable and Titanium Osteofixation Systems G.J. Buijs, E.B. van der Houwen, B. Stegenga, R.R.M. Bos, G.J. Verkerke Published in: J Oral Maxillofac Surg Nov;65(11): Chapter Mechanical Strength and Stiffness of the Biodegradable SonicWeld Rx Osteofixation System G.J. Buijs, E.B. van der Houwen, B. Stegenga, R.R.M. Bos, G.J. Verkerke Published in: J Oral Maxillofac Surg Apr;67(4): Chapter 4 79 Biodegradable and Titanium Fixation Systems in Oral and Maxillofacial Surgery: a Randomized Controlled Trial G.J. Buijs, N.B. van Bakelen, J. Jansma, J.G.A.M. de Visscher, Th.J.M. Hoppenreijs, J.E. Bergsma, B. Stegenga, R.R.M. Bos Submitted Chapter 5 93 General discussion and future perspectives

6 CHAPTER 1 GENERAL INTRODUCTION

7 CHAPTER 1 GENERAL INTRODUCTION Field of interest Traumatic injuries in the maxillofacial region and dentofacial anomalies may have considerable physical and psychological impact on patients. Therefore, major efforts should be carried out to anatomically and aesthetically restore form and function of the maxillofacial hard and soft tissues in such cases (6). The maxillofacial skeleton consists of 3 parts: the cranium, the mid-face, and the mandible. The mandible articulates with the base of the skull at the left and right temporomandibular joint and at the level of the dental occlusion, and is powered by forceful masticatory muscles. This biomechanical system allows people to perform important functions, such as chewing, swallowing, laughing, and speaking. Physically, the mandible is a heavily loaded bony structure and, consequently, its cortex is thick and compact. By contrast, the mid-face consists of thinwalled cavities, strengthened by bony buttresses absorbing forces exerted through the muscles of the maxillofacial skeleton (7). The diagnosis and treatment of facial fractures and dentofacial anomalies play a prominent role within oral and maxillofacial surgery. Through population growth, increase of traffic, industrialization, violence and sport, the field of traumatology has considerably increased. Today, of the fractures, approximately 55% are caused by traffic accidents, 20% by accidental falls, and 17% by assaults (8). The wearing of helmets and seatbelts and the general introduction of airbags in automobiles were major steps forward in the prevention of trauma. In general, good clinical results are currently achieved in both maxillofacial traumatology and dentofacial orthopedics primarily because of advanced diagnostic radiographic methods as well as refined surgical techniques and fixation materials. Diagnostic radiographic methods Diagnostic radiographic methods are essential (1) to determine the exact extent of suspected maxillofacial fractures, and (2) for the diagnosis and treatment planning of osteotomies. Three-dimensional (3D) visualization of the bony skeleton and the dentition can be obtained by Computed Tomography (CT) and is the golden standard for fractures. The images are very precise and the surgeon can determine preoperatively where the plates and screws should be placed to acquire immobilization of the bone fragments. A disadvantage of CT examination is the relatively high radiation exposure. Recently, Cone Beam Computed Tomography (CBCT) has been developed, which is faster and produces less radiation (9). Conventional images, such as a panoramic radiograph and a frontosuboccipito radiograph, are the standard recordings to assess mandibular fractures. In case of (para)median fractures, axial radiograph may provide additional information. A panoramic radiograph and a lateral cephalogram are the standard radiographs for osteotomies of the mandible and maxilla. Requirements for adequate bone healing Essential aspects for bone healing of fractures and osteotomies are sufficient vascularization, anatomical reduction, and immobilization of bone segments (7;10). The treatment of nearly all maxillofacial fractures and osteotomies is currently performed by an open surgical approach to have a better control of the (re)positioning of bone fragments (6;11). Immobilization is obtained using fixation plates and screws. Various compressive, tensile, and torsion forces need to be counteracted by the plates and screws at the fracture crevice and the osteotomy site. After most of the mandibular fractures, the bone takes over compressive forces, whereas the osteosynthesis devices counteract the lost tensile forces. This is called load sharing between the bone and the plates and screws. In case of bony defects, comminuted fractures and bi-lateral sagittal split osteotomies, a plate is fully loaded for bending forces and is called load bearing. Load sharing allows plate and screw dimensions that are much smaller than those necessary for load bearing. The next sections comprise a review of the development of different fixation systems used for immobilization. Refined surgical techniques and development of fixation material Closed fracture management In the first half of the past century maxillofacial traumata were predominantly treated in a closed (i.e. non-surgical) manner. Immobilization of bone segments was achieved with InterMaxillary Fixation (IMF) in most cases. Stainless steel ligatures were tied up along the dental arches so that the correct dental occlusion could be achieved, whereas in more difficult cases the upper or the lower jaw could additionally serve as a template. Sophisticated external frame fixation devices were applied to achieve immobilization in severe multi-fragment situations (12). An external frame was usually secured with plaster of Paris, bandages or plastic head caps (13). Figure 1. Man with fixation apparatus fixed with plaster of Paris. These devices were generally uncomfortable, patient-unfriendly and had a rather gruesome appearance (6;13). They immobilize the temporomandibular joints resulting in cartilage degeneration. Moreover, the requirements for optimal bone healing could not be acquired. For example, fractures and osteotomies above the Le Fort I level were difficult to immobilize with these external devices (6). The transfer pins from the bone segments to the external fixtures facilitate an easy entry of bacteria to the healing bone. Treatment without an open intervention impedes surgeons to anatomically re-position the bone segments. Figure 1. Man with fixation apparatus fixed with plaster of Paris Open fracture management In the second half of the past century there was a shift from closed to open surgical treatment. Besides the improved anaesthetic techniques and infection control, especially the development of the so-called training- or function-stable fixation materials, was responsible for this shift. Training-stable means moving without loading whereas function-stable means moving and loading. CHAPTER

8 CHAPTER 1 Starting with wire osteosynthesis, surgeons made bur holes through both bone fragments after careful stripping of the periostium. Subsequently, a wire was tied up through the bur holes and the ends were twisted along each other (14). Due to the open fracture management, there was a better control of repositioning the dislocated fragments (6). The fragments could better be stabilized with wire osteosynthesis compared to external fixation devices. Nonetheless, wire osteosynthesis were not able to optimally stabilize bone fragments in order to acquire training- of even function-stable fixation. The first fixation systems that obtained sufficient stability to immediately restore the functions of the maxillofacial skeleton were developed in 1957 by the Arbeitsgemeinschaft für Osteosynthese fragen (AO), a Swiss study group. This study group used the ideas of the fixation of fractures of the long bones published by Danis in 1947 (15). The emergence of these plates and screws heralded, in the 60s of last century, the era of training- and function-stable osteosynthesis system. With these systems fracture fragments could anatomically be stabilized and held in position, and could be directly and functionally loaded. With these plates and screws, it was possible to obtain a certain stress on the fracture segments against each other. Because of this stress, the fracture crevice obtained a resistance to friction and mobility. This so-called compression system was later ingeniously built into the screw holes of the plates, where the screw heads, with eccentric screw placement, could build up the required axial interfragmental compression between the bone fragments. These plates are called dynamic compression plates, or DCP plates (16-18). During the healing period, stability of the fracture is maintained for approximately 6 to 8 weeks. The acquired compression does not lead to bone necrosis, whereas the remodelling of the bone compensates for the instability that might arise from the gradual decrease of the compression. When using this type of fixation, the formation of callus, estimated as a sign of lack of stability could be prevented. Initially, plates for application in the lower jaw with bicortical screws were developed to achieve the desired stability analogous to the fixation of fractures in long bones (19-21). Given the choice for bicortical anchoring of the screws and in order to avoid damage to the roots of the teeth and nerve structures, the only safe place for these systems was the lower border of the mandible. In terms of mechanical stress, this was the most demanding and the least favourable position to compensate dislocating forces. Often, these plates were applied via an extra-oral approach and required a disadvantageous large skin incision and wide stripping of the periostium to insert and apply the voluminous plates. An advantage of these relatively large and bulky plates was that they were strong enough to bridge bony defects, bone grafts, and comminute fractures used for reconstructions. Late in the 70s, a mini-plate system for the mandible was introduced by Champy et. al. (22;23). These small plates have much smaller dimensions than the AO-plates that were used for the fixation of fractures of the facial skeleton. The system was derived from the midface fixation system launched by Michelet in 1973 (24). The size of the miniplates was adapted to a mechanically more favourable location for fixation of mandibular fractures (Figure 1). Figure 2. Favourable location of plates and screws on the mandible The plates and screws were relatively small and the plates were easier to bend. With delicate intra-oral incisions, bone segments could be visualized so that they could be repositioned anatomically while the plate could be easily inserted and gently adapted to the curvature of the maxillofacial bones. Subsequently, the screws could be inserted monocortically, leading to a firm stabilization. In this way, bone segments, even of complicated fractures and of osteotomies, could be accurately stabilized (25). Using this system, all (dislocated) mandibular fractures can be stabilized in a training-stable way with the exception of fractures involving a defect to be bridged (26). This simpler technique, as well as the benefits of an intraoral approach, meant a shift in the preference of surgical treatment of mandibular fractures in favour of the mini-plate method (27). Initially, the appearance of the mini-plate method led to a fundamental discussion of the proponents of the bicortical fixed plates obtaining absolute stability (function stable fixation) and the advocates of mono-cortically fixed mini-plates (training stable fixation). The latter were convinced that with less material on mechanically favourable locations, an adequate fixation of the fracture segments followed by undisturbed fracture healing could be achieved. Research has now shown that undisturbed healing can be achieved with both methods, provided that appropriate repositioning (i.e. anatomical reduction) of the fracture parts is combined with sufficient plate material in strength and number. By increasing the complexity of the fracture, more plate material is necessary (28-30). The materials used in this area were originally stainless steel plates, whereas titanium plates and screws are currently the golden standard. The successful development of metallic osteosynthesis devices used to stabilize fractured bone fragments was a major impulse for further development of the surgical techniques used to treat dentofacial anomalies. Orthognatic surgery went through a similar develop- CHAPTER

9 CHAPTER 1 ment for its fixation materials as did cranio-maxillofacial traumatology starting with wire osteosynthesis in combination with IMF to only plate and/or screw fixation and postoperative guiding elastics. With orthognatic surgery osteotomized jaws are put into new positions thus changing facial anatomy and dental occlusion. In a way this can be considered as non-anatomical reposition and fixation of facial fractures, often leaving gaps that are bridged with osteosynthesis plates. The mechanical properties of the fixation materials used for this type of surgery are therefore of utmost importance and can probably not be compared with fracture treatment on a one-to-one ratio. Characteristics of titanium devices Titanium plates and screws are made of pure titanium or titanium alloys. The biocompatibility (31) and the strength of titanium has been thoroughly investigated in many scientific studies. Conventional titanium fixation devices have several disadvantages, which can be summarized as follows: 1. in some patients, particularly those with thin soft tissues, the edges of the inserted (large) plates and screws can be felt. Dehiscence can also occur in situations where the overlying mucosa or skin is very thin. In extreme climates, plates and screws can lead to sensitivity to high or low temperatures; 2. migration and displacement represents the limitation of the use of titanium plates and screws in the growing bones of children or infants; 3. exact bending of the plates is an essential requirement for successful repositioning of the bone fragments. This pre-shaping is time consuming, especially when using voluminous plates; 4. titanium plates and screws interfere with imaging techniques, such as computed tomography and magnetic resonance imaging. The interference with radio-therapeutic treatment techniques is also disadvantageous. The plates and screws can block the radiotherapeutic beam resulting in an inadequate treatment; 5. the most significant disadvantage is probably the continued presence of plates and screws in the human body after the material has fulfilled its function. Despite its biocompatibility, titanium still is a foreign body for the human organism. This generates controversies among experts as to whether implant removal is necessary or not. There is consensus that a follow-up implant removal operation is sometimes indicated (5-40%) (32-34), particularly in young patients with growing bone. Implant removal implies an additional surgical procedure with all its associated disadvantages of time, costs, infection risk, discomfort, and anaesthesia. Characteristics of biodegradable devices Since about 4 decades, there is a continuous drive to explore the feasibility of biodegradable devices for the fixation of fractures and osteotomies. The introduction of biodegradable implants can be helpful in eliminating and reducing the disadvantages of titanium plates and screws. Research has revealed that biodegradable materials have limitations as well: 1. most biodegradable plates or meshes must be heated before they can be shaped. The screw holes must be drilled and tapped. This is disadvantageous for difficult and timeconsuming craniofacial operations where many plates and screws must be used; 2. low mechanical stability still represents an important issue of the biodegradable systems, particularly when used in load bearing areas such as the mandible; 3. the manufacturers of the biodegradable fixation devices have increased the dimensions due to the low mechanical strength and stiffness of the polymer based fixation devices. The enlarged dimensions could result in difficult wound closure and an increased risk to develop dehiscence; 4. to our best knowledge, there is no definitive evidence that demonstrates that biodegradable (co)polymers can be fully degraded and resorbed by the human body. However, the possible advantage of disappearing fixation devices still seems to be an appealing alternative to fix bone segments in specific situations. AIMS OF THIS THESIS The performance of the currently used titanium fixation systems has been thoroughly evaluated. Titanium systems have been proven to be adequate fixation devices except for the disadvantageous aspects mentioned above. Biodegradable fixation devices seem to be an attractive alternative as these systems can reduce or even erase the negative aspects of titanium systems. During the search for the ideal fixation system, the local anatomical circumstances, the forces exerted through the maxillofacial skeleton, as well as the advantages and disadvantages of titanium and biodegradable fixation devices should be taken into account. The general aim of this research project was to establish the effectiveness and safety of biodegradable plates and screws to fix bone segments in the maxillofacial skeleton as a potential alternative to metallic ones. More specifically, the aims of this research project were: - to review the currently available scientific evidence for the applicability of biodegrad able plates and screws for the fixation of bone segments in the maxillofacial skeleton (chapter 2); - to establish the torsion strength of titanium and biodegradable fixation screws (chapter 3.1); - to establish the tensile strength and stiffness, bending stiffness, and torsion stiffness of titanium and biodegradable fixation systems (chapter and 3.2.2) - to establish the short term effectiveness and safety (chapter 4) of biodegradable plates and screws used for fixation of fractures and osteotomies in the maxillofacial skeleton compared to conventional titanium plates and screws. CHAPTER

10 CHAPTER 2 EFFICACY AND SAFETY OF BIODEGRADABLE OSTEOFIXATION DEVICES IN ORAL AND MAXILLOFACIAL SURGERY: A SYSTEMATIC REVIEW G.J. BUIJS B. STEGENGA R.R.M. BOS Published in: J Dent Res Nov;85(11):980-9.

11 INTRODUCTION CHAPTER 2 Abstract: Background - The use of osteofixation devices should be evidence-based in order to secure uncomplicated bone healing. Numerous studies describe and claim the advantages of biodegradable over titanium devices as a bone fixation method. Objective - To systematically review the available literature to determine the clinical efficacy and safety of biodegradable devices compared with titanium devices in oral and maxillofacial surgery. In addition, related general aspects of bone surgery are discussed. Methods & materials - A highly sensitive search in the databases of MEDLINE ( ), EMBASE ( ) and CENTRAL ( ) was conducted to identify eligible studies. Eligible studies were independently evaluated by two assessors using a quality assessment scale. Results - The study selection procedure revealed four methodologically acceptable articles. Owing to the different outcome measures used in the studies, it was impossible to perform a meta-analysis. Therefore, the major effects regarding the stability and morbidity of fracture fixation using titanium and biodegradable fixation systems were qualitatively described. Conclusion & discussion - Any firm conclusions regarding the fixation of traumatically fractured bone segments cannot be drawn due to the lack of controlled clinical trials. Regarding the fixation of bone segments in orthognathic surgery, only a few controlled clinical studies are available. There does not appear to be a significant short-term difference between titanium and biodegradable fixation systems regarding stability and morbidity. However, definite conclusions, especially with respect to the long-term performance of biodegradable fixation devices used in maxillofacial surgery, cannot be drawn. Abbreviations used in this paper are: CENTRAL, Cochrane Central Register of Controlled Trials; MeSH, Medical Subject Heading; VAS, Visual Analogue Scale; and W, weight. Key words: Biodegradable, osteofixation, treatment, stability, morbidity, systematic review. Background Maxillofacial traumatology and orthognathic surgery are major fields of oral and maxillofacial surgery. Internal rigid fixation systems are used for fixation and stabilization of osteotomized or fractured bone segments (35;36). Plates and screws are generally made of titanium and are currently regarded as the golden standard (4;37;38). Titanium fixation systems can be used safely and effectively (35;39). The intrinsic mechanical properties ensure that the device dimensions are kept within acceptable limits. The handling characteristics of titanium systems are simple and efficient (40). However, titanium devices also have disadvantages. These systems interfere with radiotherapy (37;41;42) and imaging techniques. Besides, titanium implants have been associated with complications such as growth restriction and brain damage (43;44), infection, and possible mutagenic effects (45). A second intervention to remove the implants implies additional surgical discomfort, risks, and associated socio-economical costs (43;46-48). A plate removal percentage of 11.1% in Le Fort I osteotomies due to infection and plate exposure has been reported (49). In a retrospective study of 279 patients with isolated mandibular fractures, a plate removal percentage of 11.5% has been reported (50). In another study (32-34), 23 oral and maxillofacial surgeons were interviewed regarding removal of mini-plates. The authors concluded that the plate removal percentage varies between 5% and 40%. Biodegradable osteofixation systems have the possibility to degrade, thus preventing the need for a second intervention (51;52). Another advantage of biodegradable devices is their radiolucency, implying good compatibility with radiotherapy and imaging techniques (42;53;54). Besides, osteoporosis can be prevented due to the gradual transfer of functional forces to the healing bone during the disintegration process of biodegradable devices (55;56). Since the introduction of biodegradable devices in 1966 (57), the development of their mechanical properties and degradation characteristics has been extensive (58). Numerous in vitro, animal, and clinical studies have been published about positive (59-65) as well as negative results (66-69). Despite the supposed advantages of biodegradable osteofixation devices, these systems did not replace the titanium systems and are currently applied in only limited numbers (43;70). The mechanical properties are less favourable and ultimate resorption has not been proven (71). Another significant factor of the limited use is the resistance by surgeons to modify their conventional, well experienced, treatment techniques (72). The major drawback for general use of biodegradable devices is the lack of clinical evidence. CHAPTER

12 CHAPTER 2 Objectives The use of biodegradable osteofixation devices should be evidence-based in order to secure uncomplicated bone healing (73). Numerous studies describe and claim the advantages of biodegradable over titanium devices as a bone fixation method (60;74). In the present study, the currently available literature regarding the clinical efficacy and safety of biodegradable osteofixation devices compared with titanium osteofixation devices in oral and maxillofacial surgery was systematically reviewed. The research question was phrased as follows: is there a difference in stability and morbidity regarding the fixation of bone segments with biodegradable or titanium fixation devices in orthognathic and trauma surgery? The available literature regarding current relevant aspects of bone surgery will also be discussed. GENERAL ASPECTS OF BONE SURGERY Various in vitro and in vivo studies must be performed before innovative interventions can be used safely and effectively in the clinic (75). Studies that have been important for understanding the behaviour and characteristics of biodegradable and titanium osteofixation systems are reviewed in the subsequent sections. Mechanism of bone healing Fractured bone or locally damaged bone causes disruption of many blood vessels. This disruption results in local haemorrhage followed by the formation of a blood clot. Osteocytes at both sides of the fracture die due to deprivation of blood perfusion. Restoration of the fracture area starts with the clearance of the blot clot, death cells and bone matrix under the influence of revascularization. Periosteum, endosteum and surrounding tissues respond by cell proliferation. The tissue that arises between both fracture ends, and serves as a temporary bridging, is called callus. Its composition varies with site and circumstances (76;77). Cartilage is formed in parts of the callus that are not sufficiently saturated with blood. Subsequently, cartilage is transformed into bone by enchondral bone formation. If sufficient blood saturation occurs, a direct network of bars of plexiform bone is formed by endesmale bone formation. As a strong bony callus arises, it can be subjected to normal tension- and compression forces (78). Resorption and formation of bone is a dynamic and continuously changing process, which has an equilibrium defined by internal factors (mainly hormones) and external factors (mainly mechanical forces). Inadequate immobilization during the healing process causes disruption of the revascularization process. This results in the formation of a fibrous callus followed by an incomplete healing of the fracture. Too rigid fixation, on the other hand, may also cause problems. Lack of normal functional stimuli in the final stages of bone healing will inhibit the formation of new bone, while the resorption of bone still proceeds (79;80). This could result in local osteoporosis (76;77;81). Mechanical aspects Various muscles of the maxillofacial skeleton exert a wide variety of forces in different directions. This implies that it is difficult to estimate the required mechanical properties of a fixation system. Decisions regarding the required plates and screws are rarely evidence-based (82). The primary mechanical strength and stiffness of biodegradable osteofixation devices are less favourable compared to their conventional titanium counterparts. This is inherent to the use of biodegradable polymers. However, the question is whether their mechanical properties are sufficient for resisting the local deforming forces (83). The main objective in orthognathic and trauma surgery is fast, anatomical and painless functional reunion of bone segments (84). Revascularization plays an essential role in this process (78;85). Titanium plates and screws are intrinsically small, strong, and biocompatible (37). As a result, the main objectives regarding fixation management can be met. The rigidity of titanium fixation systems might also be disadvantageous. The system probably inhibits the transfer of functional forces to healing (or healed) bone, which may result in osteoporosis as was mentioned in the previous section (55;56;81). By contrast, the strength and stiffness of biodegradable fixation systems decrease with time because of the disintegration of the polymer chains, in this way ensuring progressive loading during the subsequent stages of bone healing. To compensate for the less favourable primary mechanical strength and stiffness of biodegradable devices, manufacturers increase their dimensions. This may interfere with tensionless wound closing, making the wound area more prone to infection. Enlarged dimensions restrict easy application in small areas which are difficult to access (e.g. paediatric surgery) (40). These factors imply that the field of application of biodegradable devices, in particular regarding bone fixation in the maxillofacial area, is restricted (43), whereas titanium systems may be applied almost anywhere. Despite the disadvantages of the enlarged dimensions of biodegradable systems as mentioned above, several patient series have been published regarding the successful use of biodegradable fixation systems applied in different (e.g. heavy load bearing) situations (e.g. mandibular fractures and bilateral sagittal split osteotomies). The treatment of 1883 patients, in whom craniomaxillofacial deformities were fixed with the biodegradable LactoSorb fixation system, was evaluated in a recent study (60). Regarding to the rapidly growing cranial vault, the authors noted, that fewer potential complications occurred using the biodegradable system compared with the titanium plates and screws. The BioSorb FX biodegradable fixation system has been found to be an appealing alternative for titanium fixation systems regarding orthognathic, trauma and cancer surgery, corrective cranioplasty, and fixation of bone grafts in another recent study (86). Considering the biomechanical aspects, selecting plates and screws is not always that straightforward. The surgeon should consider the (1) local deforming forces and (2) which system (biodegradable or titanium) could optimally resist the deforming forces (87), and in what configuration (number of screws in both fracture ends). CHAPTER

13 CHAPTER 2 Biocompatibility and resorption aspects Biocompatibility refers to how a material elicits a host response in a specific situation. Tissue responses to implanted material are numerous and complex. The term biocompatibility also describes aspects of interactions between implanted material and the host (88;89). The process of removal of a material by cellular activity and/or dissolution in a biological environment, is called resorption (90). Degradation is the disintegration of material into smaller parts. Biocompatibility, resorption and degradation are closely interrelated. The biocompatibility of biodegradable internal fixation devices is strongly influenced by the degradation and resorption behaviour of the polymers used (75;91). These systems are made of different polymers (e.g. poly(l-lactide), poly(d-lactide), poly-glycolide, polydioxanone, trimethylene carbonate). These materials degrade and resorb in two phases (92). During the first phase, water molecules hydrolyze the long polymer chains into shorter fragments. The molecular weight and the polymer strength decrease during this process. The second phase consists of a physiologic response of the body in which macrophages phagocyte and metabolize the short fragments which subsequently enter the citric acid cycle (93-95). Water and carbon dioxide remain and are subsequently excreted from the body, mainly through respiration. The mass of the biomaterial rapidly disappears during phase two (57;96). In addition, enzymes are supposed to play a considerable role in the degradation (97;98). Degradation and resorption processes of biodegradable polymers frequently elicit adverse tissue responses. This represents an inherent biologic tissue response (75) as occurs with every implanted material (67). Regarding orthopedic surgery, the general incidence of adverse tissue responses using fixation devices made of poly-glycolide varies from 2.0 to 46.7% (75). The incidence of adverse tissue responses is generally lower for plates and screws made of poly-lactide (75). The time between implantation and appearance of adverse tissue responses varies from weeks (48;67;99) to 4-5 years (66;100;101) for respectively poly-glycolide and poly-lactide. The clinical characteristics of the adverse tissue responses vary from a local swelling without signs of inflammation (66) to a suddenly emerging painful, erythematous, fluctuating papule which reveals a sinus discharge of liquid remnants of disintegrated implant materials (75). Radiographs obtained at the time of manifestation show osteolytic changes around the implanted material in 50% of the patients (68;102). The histopathologic picture has been characterized by an abundant polymeric debris, being surrounded by mononuclear phagocytes and multinucleated foreign-body giant cells (67;68;103;104). The possible risk factors for developing adverse tissue responses seem to be associated with the extent of vascularization, which inherently depends on the site of implantation. Moreover, the implant design appears to affect the response rate. Cylindrical pins and rods show a lower incidence of adverse tissue responses than screws. Foreign-body response rates seem to be independent of patients age and gender as well as the implanted polymer volume. The long-term ultimate biocompatibility and resorption of biodegradable plates and screws have frequently been investigated, yet remain to be established (75;105). Researchers have reported varying in vivo results. A recent histologic study (106) reported complete resorption of Resorb X and LactoSorb screws after 12 and 14 months, respectively, found by the use of a fluorescence microscope. However, bone re-modelling was not completed after 26 months. The degradation process of biodegradable implants has also been investigated through MRI (107). The authors concluded that no complete resorption had occurred after 34 months. Based on these findings, large-scale, long-term controlled clinical trials can be recommended to verify the ultimate biocompatibility and resorption characteristics of biodegradable implants and to establish evidence-based treatment methods. Characteristics of ideal osteofixation devices Considering the aspects mentioned in the previous sections, an ideal osteofixation device should (82;92): (1) be fabricated and designed with appropriate initial strength to meet the bio-mechanical demands, (2) not cause tissue responses necessitating device removal, (3) be easy to use and handle, (4) be cost-effective, and (5) be compatible with radiotherapy and imaging techniques. Regarding biodegradable osteofixation devices, the following aspects should additionally be incorporated: (6) degrade in a predictable fashion and allow for safe progressive loading during each stage of bone healing and (7) disappear completely. CONTROLLED CLINICAL STUDIES A SYSTEMATIC REVIEW METHODS Literature search To identify studies on the efficacy and safety of biodegradable osteofixation devices, a highly sensitive search was carried out in the databases of MEDLINE ( ) and EMBASE ( ). The search was supplemented with a systematic search in the Cochrane Central Register of Controlled Trials (CENTRAL) ( ). Free text words and the applied thesaurus (MeSH) regarding the search strategy are summarized in Table I. Several experts in the field of biodegradable osteofixation devices were contacted to ensure eligible studies were not overlooked. Moreover, leading oral and maxillofacial journals were screened for missing articles. To complete the search, reference lists in the obtained literature were checked for additional relevant articles. No language and time restrictions have been included in the search strategy. The search strategy was focused on three aspects: (1) terms to search the health condition of interest (i.e. fracture and osteotomies of the maxillofacial skeleton); (2) terms to search for the intervention(s) evaluated (i.e. biodegradable and titanium osteofixation device(s)); and (3) terms to search for the types of study design to be included (i.e. clinical controlled trials) (108). Free text words and MeSH terms were formulated precisely, resulting in a scrupulous primary exclusion of non clinical trials as well as studies which are rarely topic related. CHAPTER

14 Table I. Search strategy Table II. Quality of study tool (109) CHAPTER 2 #1 surger* or fracture* or trauma* or reconstruction* or orthoped* or injur* #2 explode Maxillofacial-Injuries / all subheadings #3 explode Facial-Bones / all subheadings #4 maxillofacial* or craniomaxill* or craniofacial* #5 jaw* or mandib* or maxill* #6 #1 and ( #2 or #3 or #4 or #5) #7 Absorbable-Implants / all subheadings #8 Bone-Plates / all subheadings #9 Bone-Screws / all subheadings #10 Internal-Fixators / all subheadings #11 plate* or screw* or miniscrew* or miniplate* or implant* or osteosynth* or osseointegrat* or osteofixation* or osteotom* or internal fixation #12 bioresorb* or biodegrad* or bioabsorb* or bioadsorb* or absorb* or resorb* or adsorb* #13 #12 and (#7 or #8 or #9 or #10 or #11) #14 ((clinical* in ti,ab) and (trial* in ti,ab)) or (PT:MEDS = clinical-trial) or ( Clinical-Trials / all subheadings) Dimension Control group Randomization Measurement outcome(s) Study design Conclusion(s) Intention to treat analysis Statistical analysis Adherence to study protocol Blinding Research question Loss to follow-up Outcomes Reporting of findings Patient compliance And other variables Weighting (W) CHAPTER 2 Search MEDLINE/EMBASE: #6 and #13 and #14 Search Cochrane Controlled Trial Register: #6 and #13 Total 100 Run data search: Study selection The relevance of studies was evaluated by a first selection based on title and abstract. Since the research question focuses on the efficacy and safety of biodegradable osteofixation devices in comparison with titanium devices, only controlled clinical trials (CCT) were considered for inclusion in the systematic analysis. The review was focused on studies concerning the treatment of fractures and the performance of osteotomies of the maxillofacial skeleton (i.e. Le Fort I, Le Fort II, and Le Fort III fractures and osteotomies, cranial fractures, malar fractures, mandibular fractures, and sagittal split osteotomies of the mandible). Studies involving children were also considered for inclusion. Disagreement about whether or not a study should be included was resolved by a consensus discussion. Full-text documents were retrieved of all relevant articles. The study selection procedure is outlined in figure 1. Inclusion and exclusion of studies To identify eligible studies suitable for methodological appraisal, relevant studies underwent a second selection procedure based on the completeness of the report. The following implant-related outcome measures should be evaluated: a. union/non-union of the fracture within the follow-up period; b. wound healing/infection; c. intervention with biodegradable as well as titanium osteofixation device; d. proper (control) group; e. diagnoses and indications for treatment must be well established by clinical and radiographic evaluation. Studies, meeting the above-mentioned criteria, were subjected for further methodological appraisal. Quality assessment of studies A quality assessment of the remaining studies was performed to control the influence of bias in a systematic analysis, to gain insight into potential comparisons, and to guide interpretation of findings (108). A registered methodologist and oral and maxillofacial surgeon (BS) as well as a PhD resident (GJB) assessed the methodological quality with the quality of study tool developed by Sindhu et al. (109). The quality of study tool 24 25

15 Figure 1. Algorithm of study selection procedure Identified articles - MEDLINE search: n = EMBASE search: n = 29 - CENTRAL search: n = 87 Excluded articles: - Non clinical trials - Rarely topic related consists of 53 items in 15 dimensions and is outlined in Table II. Each dimension has a specific weight (W). The included articles revealed an independent score by the two observers according to the 15 dimensions (range 0-100). Agreement regarding the weight of the individual sub-dimensions and the required minimum methodological values for each dimension was reached in a consensus meeting. Based on these minimum values, summation yielded a threshold value, which in this study was 54. If feasible, a meta-analysis was carried out provided that the primary outcome measures (defined in the individual studies) could be meaningfully combined in an overall effect-size. CHAPTER 2 Relevant articles - Fracture or osteotomy in the maxillofacial skeleton - Biodegradable osteofixation device - Clinical trials n = 35 Eligibility criteria controlled clinical trials - Union/non-union of fracture/osteotomy - Wound healing/infection - Intervention with biodegradable and titanium osteofixation device - Clinical and radiological evaluation - Follow up period > 1/2 year - Proper control group n = 5 Included for methodological appraisal n = 4 Included for meta-analyses n = 0 Excluded articles: - Non controlled trials - No fracture or osteotomy in the maxillofacial skeleton - No biodegradable osteofixation devices used Excluded articles: Inadequate reporting of Methods and Results (1) Excluded articles: Similarity of outcome measures insufficient (2-5) Statistical analysis The degree of agreement between the two observers regarding eligible studies before the consensus meeting is expressed as a percentage of agreement of unweighted Cohens s kappa. Where applicable, Cochrane Review writing software (RevMan) was used to calculate the overall effect sizes by means of the random-effects model. RESULTS The MEDLINE, EMBASE and CENTRAL search identified 122, 29 and 87 publications, respectively. Systematic assessment of these 238 articles according to the specified eligibility criteria revealed 5 possible eligible publications. Inclusion of a titanium control group appeared to be the limiting criterion in this selection, however essential for answering the research question. Inclusion of a control group and, preferably, random assignment are major aspects for controlling unknown influences and possible confounders (108;110). Checking references of relevant articles and contacting experts did not reveal additional articles. Methodological assessment of the 5 eligible publications revealed 4 methodologically acceptable articles. One article was excluded because of inadequate reporting of the methods and results (1). Inter-assessor agreement on the methodological quality of each study was 96% (unweighted kappa, 0.90; 95% CI: 0.85 to 0.96). Disagreements were generally caused by slight differences in interpretation and were easily resolved in a consensus meeting. Three studies used randomization to allocate patients to the treatment groups (2;4;5). One study allocated patients consecutively (3). LactoSorp plates and screws (W. Lorenz Surgical, Jacksonville, Florida) were used to fix bone segments in two studies (2;3). The LactoSorp fixation system has a copolymer composition of 82% L-lactide and 18% glycolide. Ferreti et al. (2002) studied mandibular splits fixed with three bi-cortical screws whereas Norholt et al. (2004) investigated the stability and relapse of Le Fort I osteotomies. One other methodologically acceptable study (4) investigated the fixation of different osteotomies using BioSorb FX plates and screws (Linvatec Biomaterials Ltd.). The BioSorb FX fixation system is made of self-reinforced (70% L-lactide, 30%DL-lactide) poly lactic acid. The most recent study (5) investigated the changes in condylar long axis and skeletal stability after bilateral sagittal split ramus osteotomy using 100% poly-l-lactic acid plates and screws (Fixsorb -MX, Takiron Co., Osaka, Japan). CHAPTER

16 CHAPTER 2 Because of the different effect-sizes used in the methodologically acceptable studies, it was impossible to perform a meta-analysis. Therefore, the major effects regarding the stability and morbidity of fracture fixation are qualitatively described in the subsequent sections. Stability Stability of fixed bone segments is an important outcome measure since the aim of fixation systems is to establish a functional, anatomical and pain-free reunion of bone segments. In the four included articles, the stability of the osteotomized segments was assessed with different methods. Cephalometric analysis was used in three of the four included studies to accurately assess the skeletal stability (2;3;5). Regarding bilateral sagittal osteotomies (5), the outcome measures SNA, SNB and ANB did not significantly differ for the titanium and PLLA group. The interincisor angle, occlusal plane angle, mandibular length, overbite, overjet, and convexity were also similar in both groups. The location of the pogonion neither showed a significant difference. In the second study (2), Le Fort I osteotomies fixed with biodegradable plates and screws revealed a significant difference in vertical dimension of the upper jaw (mean difference 0.6 mm) after 6 weeks post-operatively. The osteotomies fixed with titanium plates and screws did not present a significant difference. The authors (2) concluded that the statistical significant difference of the vertical dimension in the biodegradable group (LactoSorp ) was not clinically relevant. Ferretti et al. (3) evaluated the relapse (skeletal stability) of bilateral sagittal osteotomies. The mean transposition of the mandible fixed with three bi-cortical screws was 4.7 (sd = 1.3) and 5.5 (sd = 1.7) millimetres for respectively the titanium and biodegradable group. The mean relapse was 0.25 (sd = 1.25) and 0.83 (sd = 1.25) millimetres, respectively (not statistically significant). The clinical mobility of the bone segments was evaluated in two included studies (2;4). The first study (2) reported a slight mobility during the first 6 weeks (6 in the biodegradable group and 3 in the titanium group) whereas one case presented mobility in the biodegradable group 1 year post-operatively. The second study (4) reported that the clinical stability improved gradually over time. No difference in this respect was revealed between titanium and biodegradable fixation. In all patients, the mobility was very mild and present in the maxilla. The mobile maxillae became stable and firm in the sixth week, and no further mobility could be detected during the follow-up period. Morbidity The morbidity of osteofixation devices is evaluated in all of the included studies (2-5). Ueki et al. (5) evaluated different aspects regarding morbidity: pain on chewing (using a visual analogue scale), maximum mouth opening range (measuring the distance between the edges of the upper and lower incisors) and temporomandibular disorder (TMD) symptoms mainly based on sound (click and crepitus) on movement. Pain on post-operative chewing revealed lower VAS scores compared to pre-operative chewing in both groups. The VAS scores between both groups were nearly similar. Maximum mouth opening range did not Table III. General characteristics Conclusion Patients 2 Quality Included Completed score Type of fixation Type of treatment Study 1 Design trial No difference regarding pain on chewing and MMOR # More TMD # symptoms in degradable group No difference regarding skeletal stability Ueki et al., 2005 Randomized Mandibular split Titanium Fixorb MX Randomized Le Fort I osteotomy Titanium Very low morbidity LactoSorb Tendency for impaction in titanium group, no impaction in the degradable group Norholt et al., 2004 No significant difference regarding clinical stability and clinical morbidity Randomized Le Fort 1 osteotomy Titanium ,5 Mandibular split BioSorb FX Cheung et al., 2004 Wunderer and Schuchardt 3 Genioplasty, Hofer 4 Step 5 osteotomy Controlled Mandibular split Titanium No significant LactoSorb difference regarding Ferretti et al., 2004 clinical stability and clinical morbidity # MMOP, Maximum Mouth Opening Range; TMD, TemporoMandibular Disorder. 1 Arranged according the publication date 2 Follow up 1 year 3 Maxillary subapical osteotomy 4 Mandibular subapical osteotomy 5 Mandibular body osteotomy 28 29

17 CHAPTER 2 reveal a significant difference. The number of symptomatic joints in the titanium group was significantly less compared to the PLLA group. General clinical aspects (infection, wound dehiscence, plate exposure and palpability of plates and screws) are objectively assessed in two included studies (2;4). The inflammatory responses gradually decreased with time. The first study (2) reported wound dehiscence in 1 patient in the biodegradable group whereas the second study (4) revealed wound dehiscence in 3 patients in the titanium group (10%) and in 2 patients in the biodegradable group (6.7%). No complications occurred as result of the dehiscence. The palpability of biodegradable plates and screws decreased with time in both studies, while the palpability of titanium plates and screws increased. In the study of Cheung et al. (4), plate exposure affected 1.02% and 1.21% of the patients in the titanium group and biodegradable group respectively whereas Norholt et al. (2) discussed one patient in the biodegradable group with plate exposure (4.2%). One included study (4) reported the removal of 3 titanium (1.53%) and 6 (3.36%) biodegradable plates (as a percentage of all plates and screws used). Ferreti et al. (3) reported briefly the clinical appearance of the surgical sites. They appeared to be abnormal with respect to the evaluation criteria (swelling, discharge, pain, or discoloration of the mucosa and skin) during the post-operative 12 months. The general characteristics, results and conclusions of the included studies are summarized in Table III. GENERAL DISCUSSION Mechanical aspects Regarding the mechanical aspects, the selection of an adequate fixation system remains difficult due to varying local situations (fracture line(s), anatomy, patients and muscle activity). To guide decisions regarding the required fixation system in different clinical situations, a comparison of the initial mechanical strength and stiffness of biodegradable and titanium systems could be valuable. Moreover, the surgeon is predominantly interested in the device (functional unit) characteristics of a fixation system rather than in the material characteristics. The variability of biodegradable osteofixation systems (i.e. co-polymer composition and geometry) makes a well-funded selection difficult (82). Besides the initial mechanical characteristics of osteofixation systems, the torsion strength and stiffness of the screws are important. The screws fix the osteofixation plate against the bone segments and prevent sliding of the bone segments and the fixation system relative to each other. This ensures adequate stabilization of the bone segments. Screws also generate inter-fragmentary compression to stabilize mandibular splits, which will enhance fracture healing. The torsion strength and stiffness of the biodegradable screws are less favourable (111) compared to titanium screws, which have been reported as a disadvantage by several authors (111;112). Moreover, biodegradable polymeric screws relax when a force is continuously applied (111). These aspects may result in decreased fracture stability and possible compromised fracture healing. Biocompatibility and resorption aspects Long-term ultimate biocompatibility, as is the goal of any implanted material, is difficult to establish. Despite considerable clinical experience of fracture fixation using biodegradable materials, long term clinical studies are scarce. Moreover, studies reporting the long-term complications (66;67;101) probably represent one end of a continuous spectrum of biological responses. The majority of the cases pass sub-clinically and remain unnoticed despite the elicitation of a (small) biological host response as is the case with every implanted material (67). The degradation and resorption characteristics as well as the possibility to develop adverse tissue responses, depend largely on the nature of the implanted materials. Polylactide is a major component of the biodegradable fixation devices and the time to elicit a considerable host response is 4 to 5 years (66;100;101;113). Therefore, studies reporting the biocompatibility and degradation characteristics regarding this material should last for at least 5 years (114). However, few laboratory animals live long enough and, consequently, long-term biocompatibility experiments are difficult to design. The development of adverse tissue responses seems to originate from several different physiologic and chemical processes. Crystalline remnants and a decrease of ph (115) during degradation are probably responsible for the adverse effects of biodegradable polymers, although the local tissue tolerance and the local clearing capacity seem to be important aspects as well (67;100;116;117). The rate of crystalline remnants and decrease of ph are partly determined by the molecular structure of the biomaterial (118). Amorphous polymers degrade faster than crystalline polymers, resulting in a rapid decrease of the ph. Crystalline polymers may remain in situ for decades (92). A high blood flow rate is an essential prerequisite for successful implantation of biodegradable fixation materials, since adequate blood flow secures sufficient removal of degradation products preventing a decrease in ph (114). PDLLA implants enriched with calcium phosphates have been investigated in rats to prevent a local decrease in ph (119). The control group received pure PDLLA implants. The PDLLA implants enriched with calcium phosphates showed an increased tissue response after 72 weeks. The authors concluded that the enriched implants are not suitable for clinical use. Clinical aspects The major objective of this systematic review was to evaluate the clinical efficacy and safety of biodegradable osteofixation devices in comparison with titanium osteofixation devices used in oral and maxillofacial surgery. Unfortunately, we cannot draw any firm conclusions regarding the fixation of traumatically fractured bone segments, owing to the lack of controlled clinical trials. Studies using two randomized treatment groups are difficult to design and not (yet) available. Regarding the fixation of bone segments in orthognathic surgery, only a few controlled clinical studies (2-4) are available. There does not appear to be a significant difference in outcome between titanium and biodegradable fixation systems. Definite conclusions regarding the long-term performance of biodegradable fixation devices used in maxillofacial surgery cannot be drawn. CHAPTER

18 CHAPTER 2 The methodologically acceptable studies contain much heterogeneity. The studies individually defined the outcome measures for stability and morbidity. Moreover, the treatment modalities performed in these studies were different (Le Fort I, sagittal split osteotomies and various osteotomies). The biodegradable fixation system (LactoSorb) used, was similar in only 2 studies (2;3). Because of the heterogeneity, pooling of outcome measures was not meaningful. A primary way to establish whether a fixation system has functioned successfully is to assess the extent of clinical mobility. However, objective mobility measurements in the maxillofacial skeleton are difficult to perform. One study reports the stability according to a nominal scale: none-, slight- and gross mobility (2) while another study reports the mobility according to a binary scale: immobility versus mobility (4). One methodologically acceptable study did not even report the extent of mobility (3). In our opinion, it is essential to report the extent of mobility when investigating the clinical efficacy and safety of biodegradable osteofixation systems. Therefore, we advise the use of a binary scale. The aim of an osteofixation device is to achieve functional, pain-free re-union within a reasonable period of time (6 weeks) (120). Compromised healing or slight mobility after 6 weeks should be defined as non -union. The most recent study (5) applied postoperative inter-maxillary fixation (IMF) for 2 weeks to prevent adverse alterations of the post-operative occlusion. The authors did not know whether the PLLA plates were strong enough to stabilize the bone segments. Today, IMF is not the state of art and thus, in our opinion, improper to apply when comparing the skeletal stability of bilateral sagittal split osteotomies fixed with titanium or PLLA plates. One of the major drawbacks of the reviewed literature is the lack of sufficient follow-up. Three of the included studies (2;3;5) followed their patients only 1 year post-operatively. Another included recent study (4) followed a few of their patients for 2 years (6 out of the titanium group and 7 out of the biodegradable group) and 24 patients in both groups were evaluated for 1 year. In our opinion, the follow up periods are too short to draw definite conclusions as to whether these biodegradable implants could serve as a safe and reliable fixation method on the long term. Many authors (60;70;86) have reported patient series with longer follow up periods. As mentioned earlier, since these patient series lack a control group, an adequate comparison with titanium fixation devices has not been made in these studies. Future clinical trials should, from a biocompatibility and resorption point of view, evaluate patients for at least 5 years as mentioned in the previous section (4.2). The onset of infections seems to differ for fixation of fractures with titanium or biodegradable devices. One included study (4) reported that the infections in the biodegradable group were diagnosed after 6 weeks, 3 months, and 6 months, while those in the titanium group were diagnosed after 2 weeks, 6 weeks, and 3 months. Another included study (2) reported that 1 infection in the titanium group was diagnosed after 1 week, whereas 2 infections in the biodegradable group were diagnosed after 6 months. These clinical findings suggest that the onset of infections tend to occur later in the biodegradable groups. The authors could not explain this tendency, although one (2) suggested that it could be caused by the ongoing degradation of the plates and screws. The known causes of infection are loosened screws and wound dehiscence (4). In one of the included trials, the authors (4) report the infection percentages in terms of individual plates (1.53% in the titanium group and 1.82% in the biodegradable group) and in terms of individual patients (10% in each group). In the discussion, the authors advocate that it is more reasonable to use the plate and screw as the unit for calculation, because an infection will occur if any single component fails. However, in our opinion it is more reasonable to use the individual patient infection-percentages to calculate the percentage of infection. After all, infection percentages in terms of individual patients will gain more insight in the extent of actual re-operating procedures. Moreover, cost-effectiveness analyses are more meaningful using infection percentages in terms of individual patients. However, cost-effectiveness analysis regarding the use of biodegradable fracture fixation devices were not reported in any of the included trials (2-5). SUMMARIZING AND CONCLUDING REMARKS The implications for the clinical applicability of biodegradable osteofixation systems on the long-term remain inconclusive. There is evidence available from randomized controlled trials to support the conclusion that there is no significant difference between biodegradable and titanium osteofixation devices with regard to short-term clinical outcome, complication rate and infections in the area of orthognathic surgery. Reoperation rates do not significantly differ in the biodegradable and titanium group. A sufficient follow up (of at least 5 years) is necessary in order to draw decisive conclusions regarding the use of biodegradable implants in oral and maxillofacial surgery. Until then, we can conclude that decisions with respect to plate and screw size, number of plates and screws, and biodegradable or titanium must be made on individually relevant aspects. Relevant factors include the nature of the injury, technical considerations, and the experience of the surgeon. Since this systematic review has some implications for future research, there is an urgent need for sufficiently powered, high quality and appropriately reported randomized controlled trials with respect to biodegradable osteofixation devices versus nondegradable osteofixation devices for well-defined maxillofacial fractures and osteotomies. Future studies should include a cost-effectiveness analysis in which hospital admission costs, surgical costs (material), and the costs associated with sick leave of the patients should be analyzed. Acknowledgments The authors thank Ms. S van der Werf from the Groningen University medical library for her assistance in the elaboration of the search strategy. The authors also thank Ms. S. Shaw for correcting the American English language. CHAPTER

19 CHAPTER 3.1 TORSION STRENGTH OF BIODEGRADABLE AND TITANIUM SCREW SYSTEMS: A COMPARISON G.J. BUIJS E.B. VAN DER HOUWEN B. STEGENGA R.R.M. BOS G.J. VERKERKE Published in: J Oral Maxillofac Surg Nov;65(11):

20 INTRODUCTION CHAPTER 3.1 Abstract: Objectives- To determine: (1) the differences in maximum torque between 7 biodegradable and 2 titanium screw systems, and (2) the differences of maximum torque between hand tight and break of the biodegradable and the titanium osteofixation screw systems. Materials & Methods- Four oral and maxillofacial surgeons inserted 8 specimens of all 9 screw systems in polymethylmethacrylate (PMMA) plates. The surgeons were instructed to insert the screws as they would do in the clinic ( hand tight ). The data were recorded by a torque measurement meter. A PhD resident inserted 8 specimens of the same set of 9 screw systems until fracture occurred. The maximum applied torque was recorded likewise. Results- (1) the mean maximum torque of the 2 titanium screw systems was significantly higher than that of the 7 biodegradable screw systems, and (2) the mean maximum torque for hand tight was significantly lower than for break regarding 2 biodegradable, and both titanium screw systems. Conclusion & discussion- Based on the results, we conclude that the 1.5- and 2.0 mm titanium screw systems still present the highest torque strength compared to the biodegradable screw systems. When there is an intention to use biodegradable screws, we recommend the use of 2.0 mm BioSorb FX, 2.0 mm LactoSorb or the larger 2.5 mm Inion CPS screws. Keywords: screw; osteofixation; biodegradable; titanium; torsion strength; properties. Background Fast, anatomical and pain-free re-union of bone fragments are the essential goals in orthognathic and trauma surgery (84). Adequate reposition, stabilization and fixation of fractured or osteotomized bone segments are essential preconditions (7;121). Plates and screws are generally used for the internal stabilization and fixation of the bone segments (35;36). Screws are used to fix osteofixation plates or to position bone segments (e.g. sagittal split osteotomies) (3). During insertion, the screws occasionally break (4). Fracture of a screw occurs when the applied torque is higher than the maximum allowable torque of the screw. Removal of broken screws and re-application of screws is expensive and timeconsuming. Besides, additional operations may result in complications and subsequent compromised bone healing. It is generally acknowledged that biodegradable screws have different torsion characteristics than titanium screws. Some clinical studies reported a higher number of broken biodegradable screws compared to titanium screws (2;4). Several authors have reported this experience as a considerable disadvantage (40;111;112). The maximum torque strength differs for the various screws mainly because of the use of different materials for manufacturing (biodegradable) screws, and different geometry of those screws. The manufacturers do not specify the torque for inserting the screws. The torque to be applied for adequate tightening the screws can be defined as hand tight. The maximally applied torque is, to some extent, controlled by the construction of the screwdriver handles (diameter, hand posture, geometry, and texture). But with most handles, the maximum torque that can be applied exceeds the torque strength of the screws, so fracture of the screws might occur. An estimate of a safe torque for screws of different diameter and length is difficult, especially for biodegradable screws (82). Moreover, many surgeons are not that experienced in using polymeric screws. To guide decisions regarding the selection and application of different osteofixation screws, clarification of the differences in torque strength of biodegradable as well as titanium osteofixation screw systems could be valuable (122). CHAPTER 3.1 Objectives The objectives of this study were to determine: (1) the differences in maximum torque between 7 biodegradable and 2 titanium screw systems, and (2) the differences in maximum torque between hand tight and break of the biodegradable as well as the titanium screw systems. MATERIALS AND METHODS Seven (5 x 2.0-mm, 1 x 2.1-mm, and 1 x 2.5-mm) commercially available biodegradable as well as two (1.5- and 2.0-mm) commercially available titanium screw systems were 36 37

21 CHAPTER 3.1 Table I. Characteristics of included osteofixation screws Brand name Manufacturer (city and state) Composition Sterility Screw # Ø Screw * Biodegradable screws BioSorb FX Linvatec Biomaterials Ltd. (Tampere, Finland) SR 70L/30DL PLA Sterile 2.0 mm 6.0 mm Resorb X Gebrüder Martin GmbH & Co. (Tuttlingen, Germany ) 100 DL-Lactide Sterile 2.1 mm 7.0 mm Inion CPS 2.0 Inion Ltd. (Tampere, Finland) LDL Lactide/TMC* Sterile 2.0 mm 7.0 mm Inion CPS 2.5 Inion Ltd. (Tampere, Finland) LDL Lactide/TMC* Sterile 2.5 mm 7.0 mm LactoSorb Walter Lorenz Surgical Inc. (Jacksonville, Florida) 82 PLLA/18 PGA Sterile 2.0 mm 7.0 mm Polymax Mathys Medical Ltd. (Bettlach Switzerland) 70L/30DL PLA Sterile 2.0 mm 6.0 mm MacroPore MacroPore BioSurgery Inc. (Memphis, USA) 70L/30DL PLA Expired 2.0 mm 6.0 mm Titanium screws KLS Martin Gebrüder Martin GmbH & Co. (Tuttlingen, Germany) Titanium (pure) Sterile 1.5 mm 6.0 mm KLS Martin Gebrüder Martin GmbH & Co. (Tuttlingen, Germany) Titanium (pure) Sterile 2.0 mm 6.0 mm * = Length of screws (according the specifications of the manufacturers) # Ø = Diameter of screws (according the specifications of the manufacturers) * = Polymer composition not specified through the manufacturer investigated. The biodegradable and titanium implants were gratuitously supplied by the manufacturers. The manufacturers, with one exception (MacroPore BioSurgery Inc.), supplied sterile implants. The Macropore implants exceeded the expiry date by 6-12 months. Nevertheless, we decided to include these implants in the tests. The general characteristics of the investigated screw systems are summarized in table I. Four oral and maxillofacial surgeons were requested to insert 8 specimens of all 9 screw systems in polymethylmethacrylate (PMMA) plates. The holes were predrilled for both the titanium as for the biodegradable screws and subsequently pre-tapped (as prescribed) for the biodegradable screws according to the prescriptions of the individual manufacturers (with prescribed burs and taps). The surgeons were instructed to insert the screws as they would do in the clinic ( hand tight ). A PhD resident inserted 8 specimens of the same set of 9 screw systems until fracture occurred. The screws were inserted at room temperature, as this is the regular operating room temperature. Before insertion of the screws, the holes were irrigated with physiological fluid to simulate the in situ lubrication. The maximally applied torque was recorded by a torque measurement meter (Nemesis Howards Torque Gauge, Smart MT-TH 50 sensor; accuracy 2.5 mnm, range mnm; supplied by Hartech, Wormerveer, The Netherlands). Statistical analysis The data were analyzed using the Statistical Package of Social Sciences (SPSS), version Descriptive statistics was used to calculate means and standard deviation. The measured maximum torque of the 32 different specimens (8 specimen times four surgeons) of each screw system were averaged. To determine whether there were significant differences between the biodegradable and the titanium osteofixation screw systems, the mean maximum torques were subjected to a One-Way ANalysis Of VAriance (ANOVA). A correction for multiple testing was performed according to Dunnet T3 (equal variances not assumed). The differences between maximum torque of hand tight and break of the various screw systems were statistically compared with Student s t-tests. Differences were considered to be significant when p < 0.05 for all tests. RESULTS The mean maximum torque and standard deviation of the 9 osteofixation screws systems for hand tight are graphically plotted in figure 1. The mean maximum torque of the biodegradable systems was significantly lower compared to the mean maximum torque of both titanium systems (table II). The standard deviations of the titanium screw systems were considerable larger than those of the biodegradable screw systems. Figure 2 represents the mean maximum torque of the 9 osteofixation screw systems at break. The standard deviations of the titanium systems showed in figure 2, were lower than those of the biodegradable systems, especially when compared to the results showed in figure 1. The plot of the 2.0-mm titanium screw system did not show a standard deviation because the torque for CHAPTER

22 CHAPTER 3.1 breaking the screws exceeded the maximum limit of the torque measurement apparatus. The mean maximum torque was set at 680 mnm (as measured by the torque measurement apparatus, however not with the accuracy of 2.5 mnm). The mean maximum torque of both titanium screw systems were significantly higher than the 7 different biodegradable screw systems. With respect to the 7 biodegradable screw system, the Inion CPS 2.5 screw system represented a significantly higher torque than the other biodegradable systems for the method handtight. Regarding the method break, the mean maximum torque of the BioSorb FX, Inion CPS 2.5 and LactoSorb screw systems were significantly higher than the four remaining biodegradable screw systems. Different comparisons regarding significant differences of the various screw systems for hand tight and break are outlined in table II. Figure 3 represents the mean maximum torque of the screw systems organized by surgeon and screw system. The surgeons showed a wider distribution of the mean maximum torque of the titanium screw systems compared to the biodegradable screw systems. This corresponds to the large standard deviations for hand tight presented in figure 1. Table III presents a summary of the descriptive statistics. The mean, standard deviation, 95% confidence interval, and the range are presented and organized by method. Table III revealed that for each screw system, the mean maximum torque at break was above the mean maximum torque at hand tight. A statistical comparison of the mean maximum torque of hand tight and break for the LactoSorb, Inion CPS 2.5, titanium 1.5 mm, and titanium 2.0 mm screw systems revealed that the mean maximum torques for break were significantly higher than the mean maximum torque for hand tight (diagonal of Table II). Figure 2. Mean maximum torque regarding method Break organized by screw system Mean maximum torque (mnm) BioSorb FX 2.0 mm Inion CPS 2.5 mm Method: Break Inion CPS 2.5 mm LactoSorb 2.0 mm Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm Degradability Degradable Non degradable System Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = maximum torque measured during insertion Points in figure: represents mean maximum torque Bars: represents the standard deviation of the mean maximum torque CHAPTER 3.1 Figure 1. Mean maximum torque regarding method Handtight organized by screw system Figure 3. Mean maximum torque of four surgeons organized by method and surgeon Method: Hand tight Mean maximum torque of four surgeons Mean maximum torque (mnm) Degradability Degradable Non degradable Mean maximum torque (mnm) Chirurg Surgeon 1 Surgeon 2 Surgeon 3 Surgeon Inion CPS 2.0 mm BioSorb FX 2.0 mm Inion CPS 2.5 mm Resorb X 2.1 mm Polymax 2.0 mm Macropore 2.0 mm LactoSorb 2.0 mm Titanium 2.0 mm Titanium 1.5 mm Inion CPS 2.0 mm BioSorb FX 2.0 mm Macropore 2.0 mm LactoSorb 2.0 mm Inion CPS 2.5 mm Resorb X 2.1 mm Polymax 2.0 mm Titanium 2.0 mm Titanium 1.5 mm System Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = maximum torque measured during insertion Points in figure: represents mean maximum torque Bars: represents the standard deviation of the mean maximum torque System Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = maximum torque measured during insertion Points in figure: represents mean maximum torque Surgeons: represents the four surgeons who inserted the screws 40 41

23 Table II. Statistical differences between osteofixation screws System BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm BioSorb FX 2.0 mm NS S NS NS S S S S S Inion CPS 2.0 mm NS NS S S NS NS NS S S Inion CPS 2.5 mm S S S NS S S S S S LactoSorb 2.0 mm NS S S S S S S S S Macropore 2.0 mm S S S S NS NS NS S S Polymax 2.0 mm S S S S NS NS NS S S Resorb X 2.1 mm S S S S NS NS NS S S Titanium 1.5 mm S S S S S S S S S Titanium 2.0 mm S S S S S S S S S Method = Hand tight Method = Break Diagonal = Hand tight versus Break S = Significant NS = Non Significant Table III. Summary of descriptive statistics Method = Hand tight System Mean* SD* 95% Confidence Interval Range Lower Bound* Upper Bound* Lowest value* Highest value* BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm Method = Break System Mean* SD* 95% Confidence Interval Range Lower Bound* Upper Bound* Lowest value* Highest value* BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm SD = Standard Deviation *in mnm 42 43

24 CHAPTER 3.1 DISCUSSION The differences in maximum torque found for the studied systems can be explained by the different screw diameters (1.5-, 2.0-, 2.1- and 2.5 mm), different (co-polymer) compositions, different geometry (pitch and shaft) of the screws, different tools used to insert the screws, different ages of the screws, and different methods to sterilize the screws. As expected, the use of titanium for manufacturing osteofixation screws revealed a high maximum torque strength whereas the use of polymers revealed a significantly lower torque strength. A surprising finding was the significant mean maximum torque difference of the BioSorb FX, Inion CPS 2.5 and LactoSorb screw systems compared to the remaining four biodegradable screw systems for the method break. The self-reinforced polymers of the BioSorb FX screw system, the larger dimensions of the 2.5 mm Inion CPS screws, and the ponderous geometry of the LactoSorb screws are probably responsible for the high maximum torque. The large standard deviations of the 2 titanium screw systems presented in figure 1 are probably caused by the higher maximum torque. After all, when surgeons apply higher torque forces, this inevitably implies loss of accuracy. The comparison of the maximum torque of hand tight and break for the individual screw systems revealed statistically significant differences for 4 (LactoSorb, Inion CPS 2.5, titanium 1.5 mm, and titanium 2.0 mm) of the 9 osteofixation screw systems (diagonal Table II). In the case of individual biodegradable screws (Inion CPS 2.0 mm, Inion CPS 2.5 mm, Macropore 2.0 mm, and Resorb X 2.1 mm), the lowest torque at break was not always above the highest torque of hand tight. Besides, the 95% confidence intervals of the maximum torque with respect to break and hand tight of biodegradable screws did overlap (Table III). These two aspects indicate that the torsion characteristics of biodegradable screws are not always that repeatable. For analyzing the results, the data of the four surgeons have been combined in order to reduce the influence of outliers and to determine statistical significant differences. The results of the independent surgeons are graphically presented in figure 3. Note the large differences in mean maximum torque regarding the 2 titanium systems compared to the 7 biodegradable systems. Statistical analysis yielded no significant differences between most surgeons except for two surgeons. This is largely due to the statistical influence of the large differences in mean maximum torque for titanium screws. Despite the significant difference between the two surgeons, the data were combined. After all, combining the results of the four surgeons should be allowed because the insertion torque of screws of maxillofacial surgeons should be approximately equal. Investigating 7 different biodegradable screws theoretically implies 7 learning curves, as is the case with every new technique (64;123;124). These learning curves could influence the results and consequent statistically significant differences. To find out whether the learning curves affected the results, the screw 1- and 2- data have been deleted for every surgeon and system. The raw data were then analyzed (6 instead of 8 screws) again. Eliminating the first 2 screws did not reveal different statistically (significant) results between the osteofixation screw systems. Statistically significant differences do not necessarily imply differences to be clinically relevant. With respect to the investigated osteosynthesis screws in this study, it is questionable whether the statistically significant differences are clinically relevant. The large significant differences between titanium screws and biodegradable screws in mean maximum torque are clinically relevant, although the field of application may be different. In contrast, the statistically significant differences between some of the 7 biodegradable devices regarding the method hand tight are not clinically relevant, because they are considered to be too small. Moreover, it has been reported that biodegradable devices physically relax under constant force (a process called creep). In this case, the applied torque is counteracted by the reorganizing polymer chains (111). Titanium screws do not undergo this material relaxation. The significant differences between some of the 7 biodegradable devices for the method break are of clinical importance, because biodegradable screws can fracture easily during insertion. The significant differences of maximum torque for hand tight and break of 2 biodegradable (Inion CPS 2.5, and LactoSorb) as well as both titanium screw systems presented in the current study are clinically relevant. After all, screws will break easily during insertion, when the differences between hand tight and break are small. The objectives of this investigation were to determine: (1) the differences in mean maximum torque between 7 biodegradable and 2 titanium screw systems, and (2) the differences of mean maximum torque between hand tight and break of the biodegradable as well as the titanium osteofixation screw systems. This study has presented that: (1) the mean maximum torque of titanium screw systems was significantly higher than of the biodegradable screw systems, and (2) the mean maximum torque of all 9 screw systems at break was (significantly) higher than at hand tight. Based on the results and discussion points mentioned above, we can conclude that the 1.5- and 2.0 mm titanium screw systems still present the highest torque strength compared to the biodegradable screw systems. When there is an intention to use biodegradable screws, we would recommend the use of 2.0 mm BioSorb FX, 2.0 mm LactoSorb or the larger 2.5 mm Inion CPS screws. Acknowledgements We would like to thank, prof. dr. G.M. Raghoebar, dr. F.K.L. Spijkervet and dr. J. Jansma for inserting the osteofixation screws. The authors also would like to thank dr. H. Groen and dr. M.M. Span for their statistical assistance. The gratuitously supply of biodegradable screws through the manufacturers (Linvatec Biomaterials Ltd., KLS Martin, Inion Ltd., Walter Lorenz Surgical Inc., Synthes, and Macropore Inc.) was gratefully appreciated. CHAPTER

25 CHAPTER MECHANICAL STRENGTH AND STIFFNESS OF BIODEGRADABLE AND TITANIUM OSTEOFIXATION SYSTEMS G.J. BUIJS E.B. VAN DER HOUWEN B. STEGENGA R.R.M. BOS G.J. VERKERKE Published in: J Oral Maxillofac Surg Nov;65(11):

26 INTRODUCTION CHAPTER Abstract: Objective - The objective of this study was to present relevant mechanical data in order to simplify the selection of an osteofixation system for situations requiring immobilization in oral and maxillofacial surgery. Materials & Methods - 7 biodegradable and 2 titanium osteofixation systems were investigated. The plates and screws were fixed to 2 polymethylmethacrylate (PMMA) blocks to simulate bone segments. The plates and screws were subjected to tensile, side bending, and torsion tests. During tensile tests, the strength of the osteofixation system was monitored. The stiffness was calculated for the tensile, side bending, and torsion tests. Results - The two titanium systems (1.5 mm and 2.0 mm) presented significantly higher tensile strength and stiffness compared to the 7 biodegradable systems (2.0 mm, 2.1 mm, and 2.5 mm). The 2.0 mm titanium system revealed significantly higher side bending and torsion stiffness than the other 7 systems. Conclusion & discussion - Based on the results of the current study, it can be concluded that the titanium osteofixation systems were (significantly) stronger and stiffer than the biodegradable systems. The BioSorb FX, LactoSorb, and Inion CPS 2.5 mm systems have high mechanical device strength and stiffness compared to the investigated biodegradable osteofixation systems. With the cross-sectional surface taken into account, the Bio- Sorb FX system (with its subtle design), proves to be the far more superior system. The Resorb X and MacroPore systems present to be, at least from a mechanical point of view, the least strong and stiff systems in the test. Key words: osteofixation system; biodegradable; titanium; mechanical; strength; stiffness; properties. Background Sufficient revascularization, anatomical reduction, and proper immobilization of bone segments are essential aspects of the healing of fractures and osteotomies (7;10). Immobilization of bone fragments is currently obtained by the use of osteofixation plates and screws (125;126). The plates and screws are applied subperiostally in order to secure sufficient revascularization (7). These fixation devices must withstand the local deforming forces that are exerted through the maxillofacial muscles. Currently, titanium fixation systems are successfully used to realize adequate immobilization (39). These systems, however, have several disadvantages: (1) the need for a second intervention to remove the devices, if indicated (46-48), (2) interference with imaging or radio-therapeutic techniques (37;41;127), (3) possible growth disturbance or mutagenic effects (37;41;43-45), (4) brain damage (44;128), (5) and thermal sensitivity (129). Biodegradable dissolving fixation systems could reduce the problems associated with titanium systems (74). However, these systems are mechanically weaker than titanium systems due to the use of biodegradable polymers. Moreover, adverse reactions to the degradation products have been reported (66;67;100;114). Despite these disadvantages, there is a continuous drive to explore fixation devices which will dissolve when bone healing has been occurred (4). In order to investigate whether biodegradable systems are proper alternatives for titanium systems, they have been the subject of research for decades (58). Nevertheless, the mechanical properties of biodegradable systems have hardly been objectively compared in the scientific literature. In addition, many biodegradable fixation systems with a great variety in dimensions and co-polymer compositions are commercially available. As a result, the mechanical characteristics differ substantially, which consequently hampers surgeons to select an adequate fixation system for a specific situation (82). Determining the different mechanical properties of titanium and biodegradable osteofixation systems could support the procedure of finding the right fixation system for the right situation (122). CHAPTER Objectives The objective of this study was to present relevant mechanical data in order to simplify the selection of an osteofixation system for situations requiring immobilization in oral and maxillofacial surgery. MATERIALS AND METHODS The specimens to be investigated were 7 commercially available biodegradable (5 x 2.0 mm, 1 x 2.1 mm, and 1 x 2.5 mm) and 2 commonly used commercially available titanium (1.5 mm and 2.0 mm) osteofixation systems. The general characteristics of the included plates and screws are summarized in table I

27 CHAPTER Table I. Characteristics of included osteofixation systems Plate Thickness* Plate Width* Plate Length* Screw Length* Screw Diameter* Brand name Manufacturer (city and state) Composition Sterility Biodegradable systems BioSorb FX Linvatec Biomaterials Ltd. SR 70L/30DL PLA Sterile 2.0 mm 6.0 mm 25.5 mm 5.5 mm 1.3 mm (Tampere, Finland) Resorb X Gebrüder Martin GmbH & Co. 100 DL-Lactide Sterile 2.1 mm 7.0 mm 26.0 mm 6.0 mm 1.1 mm (Tuttlingen, Germany ) Inion CPS 2.0 mm Inion Ltd. (Tampere, Finland) LDL Lactide/TMC/PGA Sterile 2.0 mm 7.0 mm 28.0 mm 7.0 mm 1.3 mm Inion CPS 2.5 mm Inion Ltd. (Tampere, Finland) LDL Lactide/TMC/PGA Sterile 2.5 mm 6.0 mm 32.0 mm 8.5 mm 1.6 mm LactoSorb Walter Lorenz Surgical Inc. 82 PLLA 18 PGA Sterile 2.0 mm 7.0 mm 28.5 mm 7.0 mm 1.3 mm (Jacksonville, Florida) Polymax Mathys Medical Ltd. 70L/30DL PLA Sterile 2.0 mm 6.0 mm 28.0 mm 6.0 mm 1.3 mm (Bettlach Switzerland) MacroPore BioSurgery Inc. 70L/30DL PLA Expired 2.0 mm 6.0 mm 25.0 mm 6.7 mm 1.2 mm (Memphis, USA) MacroPore Titanium systems KLS Martin Gebrüder Martin GmbH & Co. Titanium (pure) Sterile 1.5 mm 6.0 mm 18.5 mm 3.5 mm 0.6 mm (Tuttlingen, Germany) KLS Martin Gebrüder Martin GmbH & Co. Titanium (pure) Sterile 2.0 mm 6.0 mm 25.5 mm 5.0 mm 1.0 mm (Tuttlingen, Germany) * = according the specifications of the manufacturers. The non-sterile titanium plates and screws were sterilized in our department in the usual manner. The manufacturers of the biodegradable systems supplied sterile implants, with the exception of the MacroPore implants of which the expiry date was passed (average 6-12 months). The plates under investigation were 4-hole extended plates. Eighteen plates and 72 screws of each system were subjected to three different mechanical tests. The osteofixation plates and screws were fixed to 2 polymethylmethacrylate (PMMA) blocks that simulated bone segments. There was no interfragmentary contact to simulate the most unfavourable clinical situation. Two screws were inserted in both PMMA blocks according to the prescriptions of the individual manufacturer (with prescribed burs and taps). The applied torque for inserting the screws was measured to check whether it was comparable to the clinically applied torque ( hand tight ) defined in a previous study (130). The holes were irrigated with saline before insertion of the screws, to simulate the in situ lubrication. The two PMMA blocks, linked by the osteofixation device (1 plate and 4 screws) were restored in a water tank containing water of 37.2 degrees Celsius for 24 hours to simulate the relaxation of biodegradable screws at body temperature (111). The tests were performed in another tank containing water at the same temperature to simulate body temperature. Saline was not used because of possible corrosion of the test- and environment set-up. Omitting the use of saline was expected not to be of influence to the test results. Figure 1. Tensile test set-up CHAPTER

28 CHAPTER Figure 2. Side bending test set-up Figure 3. Torsion test set-up The plates and screws were subjected to tensile, side bending, and torsion tests. The tensile test was performed as a standard loading test (figure 1). Side bending tests were performed to simulate an in vivo bi-lateral sagittal split osteotomy (BSSO) situation (figure 2). Torsion tests were performed to subject the osteofixation devices to high torque in order to simulate the most unfavourable situation (figure 3). The 2 PMMA blocks, linked by the osteofixation device, were mounted in a test machine (Zwick/Roell TC-FR2, 5TS. D09, 2.5kN Test machine. Force accuracy 0.2%, positioning accuracy mm; Zwick/ Roell Nederland, Venlo, The Netherlands). Regarding the tensile tests, the 2 PMMA blocks and thus the osteofixation plate were subjected to a tensile force with a constant speed of 5 mm/min until fracture occurred (according to the standard ASTM D638M). For the side bending test the 2 PMMA blocks were supported at their ends whereas the plates were loaded in the centre of the construction with a constant speed of 30 mm/min (with this speed the outer fibers were loaded as fast as the fibers of the osteofixation system in the tensile test) until the plate was bended 30 degrees. For the torsion test the 2 PMMA blocks were twisted along the long axis of the osteofixation system with a constant speed of 90 degrees/min (with this speed the outer fibers were loaded as fast as the fibers of the osteofixation system in the tensile test) until the plate was turned 160 degrees. During testing the applied force was recorded by the load cell of the test machine. Both force and displacement were measured with a sample frequency of 500 hertz and graphically presented in force-displacement diagrams. During tensile tests, the strength of the osteofixation system was monitored. The stiffness was calculated for the tensile, side bending and torsion tests by linking the 25% and 75% points (to exclude inaccuracies of the start and end of the curves) of the maximum force on the force-displacement curves and determining the direction-coefficients of the curves. CHAPTER Statistical analysis Statistical Package of Social Sciences (SPSS, version 12.0) was used to analyze the data. Mean and standard deviation were calculated to describe the data. To determine whether there were significant differences between the biodegradable and the titanium osteofixation systems in (1) tensile strength and stiffness, (2) side bending stiffness, and (3) torsion stiffness, the maximum values were subjected to a One-Way ANalysis Of VAriance (ANOVA). A correction for multiple testing was performed according to Dunnet T3 (equal variances not assumed). Differences were considered to be significant when p < 0.05 for all tests. RESULTS The torques used to insert the screws of the 9 osteofixation systems regarding the tensile, side bending, and torsion tests are outlined in table II. The mean torques as well as the standard deviations for each system in all three tests were nearly similar. The mean tensile strength and stiffness of the 9 osteofixation systems are graphically 52 53

29 Table II. Applied torque of inserted osteofixation screws Figure 4. Mean tensile strength organized by system Test System Mean* SD* Method: Strength Tensile Test Tensile BioSorb FX Degradability Degradable Inion CPS Inion CPS LactoSorb MacroPore Polymax Mean strength (N) Non degradable ResorbX KLS CHAPTER KLS Side Bending BioSorb FX Inion CPS Inion CPS LactoSorb BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm System Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.0 mm Titanium 1.5 mm Titanium 2.0 mm Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = mean strength in Newton s Points in figure: represents mean strength Bars: represents the standard deviation of the mean strength CHAPTER MacroPore Polymax Figure 5. Mean tensile stiffness organized by system ResorbX Method: Stiffness Tensile Test KLS KLS Degradability Degradable Non degradable Torsion BioSorb FX Inion CPS Inion CPS LactoSorb MacroPore Polymax Mean Stiffnes (N/mm) *in mnm SD = Standard Deviation ResorbX KLS KLS BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm System Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.0 mm Titanium 1.5 mm Titanium 2.0 mm Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = mean stiffness in Newton/mm Points in figure: represents mean stiffness Bars: represents the standard deviation of the mean stiffness 54 55

30 Table IV. Summary of descriptive statistics tensile test CHAPTER Table III. Significance between osteofixation systems Titanium 2.0 mm Titanium 1.5 mm Resorb X 2.1 mm Polymax 2.0 mm MacroPore 2.0 mm LactoSorb 2.0 mm Inion CPS 2.5 mm Inion CPS 2.0 mm BioSorb FX 2.0 mm System BioSorb FX 2.0 mm XXXX S S S S S S S S Inion CPS 2.0 mm S XXXX S S S NS S S S Inion CPS 2.5 mm S NS XXXX S S S S S S LactoSorb 2.0 mm NS S S XXXX S S S S S MacroPore 2.0 mm S NS NS S XXXX NS NS S S Polymax 2.0 mm S NS NS S NS XXXX S S S Resorb X 2.1 mm S S S S NS S XXXX S S Titanium 1.5 mm S S S S S S S XXXX S Titanium 2.0 mm S S S S S S S S XXXX Underline = Tensile strength Italic = Tensile stiffness S = Significant NS = Non Significant Tensile strength System Mean^ SD^ 95% Confidence Interval Lower Bound^ Upper Bound^ BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm MacroPore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm Tensile stiffness System Mean* SD* 95% Confidence Interval Lower Bound* Upper Bound* BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm MacroPore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm ^ in N *in N/mm SD = Standard Deviation presented in figure 4 and 5, respectively. The two titanium systems (1.5 mm and 2.0 mm) presented significantly higher tensile strength and stiffness compared to the biodegradable systems (2.0 mm, 2.1 mm, and 2.5 mm). Regarding the biodegradable systems, the BioSorb FX, Inion CPS 2.5 mm, and LactoSorb systems presented a significantly higher tensile strength whereas the BioSorb FX and LactoSorb systems presented a significantly higher tensile stiffness compared to the other biodegradable systems. The differences between the systems are outlined in table III. The standard deviations for the systems regarding the tensile strength and stiffness were small. A summary of the descriptive statistics is presented in table V

31 Figure 6. Mean side bending stiffness organized by system CHAPTER Mean Stiffnes (N/mm) Mean Stiffnes (N/mm) Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = mean stiffness in Newton/mm (deducted unit) Points in figure: represents mean stiffness Bars: represents the standard deviation of the mean stiffness Figure 7. Mean torsion stiffness organized by system Method: Stiffness Side Bending Test BioSorb FX 2.0 mm BioSorb FX 2.0 mm Inion CPS 2.5 mm Inion CPS 2.5 mm LactoSorb 2.0 mm System Macropore 2.0 mm Polymax 2.0 mm Mean: Stiffness Torsion Test Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm System Macropore 2.0 mm Polymax 2.0 mm Resorb X 2.0 mm Resorb X 2.0 mm Titanium 1.5 mm Titanium 1.5 mm Titanium 2.0 mm Titanium 2.0 mm Legend: X-axis = brand names of the investigated osteofixation systems Y-axis = mean stiffness in Newton/mm (deducted unit) Points in figure: represents mean stiffness Bars: represents the standard deviation of the mean stiffness. Degradability Degradable Non degradable Degradability Degradable Non degradable Table V. Significance between osteofixation systems Titanium 2.0 mm Titanium 1.5 mm Resorb X 2.1 mm Polymax 2.0 mm MacroPore 2.0 mm LactoSorb 2.0 mm Inion CPS 2.5 mm Inion CPS 2.0 mm BioSorb FX 2.0 mm System BioSorb FX 2.0 mm XXXX S S S S S S NS S Inion CPS 2.0 mm S XXXX S S S S S NS S Inion CPS 2.5 mm S S XXXX NS S S S NS S LactoSorb 2.0 mm S NS S XXXX S S S NS S MacroPore 2.0 mm S S S S XXXX S NS NS S Polymax 2.0 mm NS S S S S XXXX S NS S Resorb X 2.1 mm S S S S S S XXXX NS S Titanium 1.5 mm S S S S NS S S XXXX S Titanium 2.0 mm S S S S S S S S XXXX Underline = Side bending stiffness Italic = Torsion stiffness S = Significant NS = Non Significant CHAPTER

32 Table VI. Summary of descriptive statistics torsion and bending test Side bending stiffness System Mean* SD* 95% Confidence Interval Lower Bound* Upper Bound* BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm MacroPore 2.0 mm Polymax 2.0 mm deviations of the biodegradable systems were small, while the 2.0 mm titanium system revealed a higher standard deviation too (in table VI). The mean torsion stiffness of the 9 osteofixation systems is graphically plotted in figure 7. As presented with the side bending stiffness, the torsion stiffness of the 2.0 mm titanium system was significantly higher compared to the remaining systems. The standard deviations of the biodegradable and 1.5 mm titanium systems were small, particularly compared to the standard deviation of the 2.0 mm titanium system. The mean torsion stiffness for the 1.5 mm titanium and 2.0 mm MacroPore system were nearly equal revealing non significance between these two systems. The Inion CPS 2.5 mm system presented by far the highest torsion stiffness of the biodegradable systems. Comparisons of the differences between the 9 osteofixation systems are outlined in table IV. Table VI presents a summary of the descriptive statistics of the side bending and torsion tests. Resorb X 2.1 mm Titanium 1.5 mm DISCUSSION CHAPTER Titanium 2.0 mm Torsion stiffness System Mean* SD* 95% Confidence Interval Lower Bound* Upper Bound* BioSorb FX 2.0 mm Inion CPS 2.0 mm Inion CPS 2.5 mm LactoSorb 2.0 mm MacroPore 2.0 mm Polymax 2.0 mm Resorb X 2.1 mm Titanium 1.5 mm Titanium 2.0 mm *in N/mm SD = Standard Deviation The mean side bending stiffness of the 9 osteofixation systems is plotted in figure 6. The 2.0 mm titanium system revealed significantly higher side bending stiffness compared to the other 8 systems. The 1.5 mm titanium and the BioSorb FX system presented a nearly similar mean side bending stiffness. The side bending stiffness of the BioSorb FX system was significantly higher compared to the other 6 biodegradable systems, whereas significance was not reached for the 1.5 mm titanium system mainly because of the large standard deviation of the mean of the 1.5 mm titanium system (see table IV). The nonsignificant results were additionally illustrated by the 95% confidence interval of the 1.5 mm titanium system which overlaps the interval of the BioSorb FX system. The standard The differences in strength and stiffness can be explained by many different factors, including dimension (1.5 mm, 2.0 mm, 2.1 mm, and 2.5 mm), (co-polymer) compositions, geometry of the plates and screws, ageing of the plates and screws, and methods to sterilize and manufacture the plates and screws. Due to the fact that the differences between the osteofixation systems are multi-factorial, it remains difficult to pose (a) specific reason(s). The maxillofacial muscles exert high forces in different directions (7). Consequently, it is difficult to simulate the in situ conditions in in vitro situations. To obtain clinical valuable information regarding the selection of an osteofixation system, the tensile strength and stiffness, side bending stiffness, and torsion stiffness were investigated as mentioned above. Adequate tensile strength and stiffness of an osteofixation system is essential for fixation of fractures and osteotomies. The osteofixation system is inevitably exposed to tensile forces when adequately repositioned bone segments are exposed to local deforming forces (22;23;44;131). The side bending test has been performed in order to simulate the bi-lateral sagittal split osteotomies (BSSO) of the mandible (132). The BSSO procedure is often performed in oral and maxillofacial surgery (35). The torsion test was used to simulate the torsion forces that are developed in the area between the two canine teeth when a median fracture of the mandible is present. These torsion forces, however, are predominantly counteracted by the interfragmentary fracture segments (133). A second argument to subject the osteofixation system to the torsion test, is that torsion forces are extraordinary destructive for osteofixation systems. During torsion of the PMMA blocks, they were prevented to move along the long axis of the system in order to additionally load the system to tensile forces. This simulates the most unfavourable in situ situation imaginable. Another important aspect of simulating the in situ situation was to test the system as it is used and applied in the clinic. The plates and screws were fixed with prescribed burs and taps. Fixing the plates with corresponding screws will provide more CHAPTER

33 CHAPTER clinical relevant information rather than fix the plates with metal screws (122). In this way, information on the entire system s (device) mechanical characteristics was obtained. The stiffness was calculated in all three tests (tensile, side bending, and torsion), while the strength is reported in just one case (tensile test). The stiffness of an osteofixation system is a more clinically applicable characteristic (134). Contrary to the stiffness, the maximum strength will only become relevant when the bone segments are separated more than a few millimeters which inherently results in compromised bone healing. Enlargement of the healing period is the result, and loosening of the screws and plates, or infection is possible (134). The stiffness was calculated from the raw data as described in the materials and methods section. Determining the 25% Fmax and 75% Fmax point as well as the corresponding displacement implies loss of accuracy due to the limited sample frequency (500 Hz.). This results in higher relative standard deviations when comparing the tensile strength. The small standard deviations regarding the tensile strength (predominantly the titanium systems), elucidate that the method of testing and the test hardware were properly designed regarding reproducibility. The high standard deviations concerning the stiffness of the titanium systems, however, in both the torsion (titanium 2.0 mm) and side bending (titanium 1.5 en 2.0 mm) tests, did not support that obviously the assumption of proper method and hardware design. The explanation for these phenomena could be the measurement imprecision mentioned above or the variety in mechanical properties of the specimens of each system. Conspicuous are the torsion and side bending stiffness of the 1.5 mm titanium system and 4 (BioSorb FX, Inion CPS 2.0, Inion CPS 2.5, and LactoSorb) of the biodegradable systems which were nearly in the same range of stiffness. This is most probably a result of the smaller dimensions of the 1.5 mm titanium system. Table IV reveals significant differences between the side bending stiffness of the biodegradable systems (caused by the small standard deviations) while the differences between the 1.5 mm titanium and the biodegradable systems were non significant. Titanium osteofixation systems were (significantly) stronger and stiffer than biodegradable systems. Despite the favourable mechanical properties of these systems compared to the biodegradable systems, the question arises whether the biodegradable systems pose adequate resistance to the local deforming forces in order to achieve adequate bone healing in patients (83). After all, the disappearance of a fixation system when bone union of the bone segments has been obtained, is still very appealing. The question mentioned above, can only be answered through well-designed randomized clinical trials which compare biodegradable and titanium osteofixation systems. The present study, however, provides well-funded information to help surgeons to select a mechanically potent bone fixation system for restoring, fixing, and stabilizing bone segments in specific situations in the maxillofacial area. The objective of this study was to present relevant mechanical data in order to simplify the selection of an osteofixation system for situations requiring immobilization in oral and maxillofacial surgery. This study has presented that the tensile strength and stiffness of both titanium systems were significantly higher than the biodegradable systems, whereas the differences between the biodegradable systems also revealed significance in most cases with regard to tensile strength as well as stiffness. Moreover, it showed that the side bending stiffness of the titanium 2.0 mm was significantly higher than the 8 remaining systems. The BioSorb FX revealed high side bending stiffness too in comparison to the other biodegradable systems, with both Resorb X and MacroPore at the lower side. Finally, this study has shown that the torsion stiffness of the titanium 2.0 mm system was high compared to the other systems. Based on the results of the current study, it can be concluded the BioSorb FX, Inion CPS 2.5 and LactoSorb systems represent the highest strength and stiffness s amongst the investigated biodegradable osteofixation systems. With the cross-sectional surface taken into account, the BioSorb FX system (with its subtle design), proves to be the far more strong and stiff system. The Resorb X and MacroPore systems are, at least from a mechanical point of view, the least strong and stiff systems in the test. Acknowledgements The gratuitously supply of titanium as well as biodegradable plates and screws through the manufacturers (Linvatec Biomaterials Ltd., Gebrüder Martin GmbH & Co., Inion Ltd., Walter Lorenz Surgical Inc., Mathys Medical Ltd., and MacroPore BioSurgery Inc.) was gratefully appreciated. The authors also would like to thank dr. H. Groen for his statistical assistance. Mr. J. de Jonge is acknowledged for the fabrication of the test set-ups. CHAPTER

34 CHAPTER MECHANICAL STRENGTH AND STIFFNESS OF THE BIODEGRADABLE SONICWELD RX OSTEOFIXATION SYSTEM G.J. BUIJS E.B. VAN DER HOUWEN B. STEGENGA R.R.M. BOS G.J. VERKERKE Published in: J Oral Maxillofac Surg Apr;67(4):782-7.

35 INTRODUCTION CHAPTER Abstract: Objective - To determine the mechanical strength and stiffness of the new 2.1 mm biodegradable ultra-sound activated SonicWeld Rx (Gebrüder Martin GmbH & Co., Tuttlingen, Germany) osteofixation system in comparison with the conventional 2.1 mm biodegradable Resorb X (Gebrüder Martin GmbH & Co., Tuttlingen, Germany) osteofixation system. Materials & Methods - The plates and screws were fixed to 2 polymethylmethacrylate (PMMA) blocks to simulate bone segments and were subjected to tensile, side bending, and torsion tests. During testing, force and displacement were recorded and graphically presented in force-displacement diagrams. For the tensile tests, the strength of the osteofixation system was measured. The stiffness was calculated for the tensile, side bending, and torsion tests. Results - The tensile strength and stiffness as well as the side bending stiffness of the SonicWeld Rx system presented up to 11.5 times higher mean values than the conventional Resorb X system. The torsion stiffness of both systems presents similar mean values and standard deviations. Conclusion & discussion - The SonicWeld Rx system is an improvement in the search for a mechanically strong and stiff as well as a biodegradable osteofixation system. Future research should be done in order to find out whether the promising in vitro results can be transferred to the in situ clinical situation. Key words: plate; screw; biodegradable; titanium; mechanical; strength; stiffness; properties; SonicWeld Rx. Abbreviations: PMMA, PolyMethylMethAcrylate; SPSS, Statistical Package of Social Sciences; BSSO, Bi-lateral Sagittal Split Osteotomy; Background Biodegradable plates and screws are used increasingly in today s oral and maxillofacial practice. These biodegradable plates and screws have several advantages over conventional titanium plates and screws. There is (1) no need for a second intervention to remove the devices (46-48), (2) no interference with imaging or radio-therapeutic techniques (37;41;127), (3) no possible growth disturbance or mutagenic effects (37;41;43-45), (4) no potential brain damage (44;128), (5) and no thermal sensitivity (129). However, the use of biodegradable plates and screws also has introduced several disadvantages. First, the boreholes need to be tapped before the screws can be inserted which is time-consuming. A second disadvantage could be that the biodegradable plates and screws represent inferior mechanical strength and stiffness compared with conventional titanium plates and screws (135). In order to resolve these disadvantages, a new biodegradable osteofixation system, SonicWeld Rx, has been developed. In contrast to conventional biodegradable osteofixation systems, tapping of the cortical bone layer is not necessary before inserting the SonicWeld Rx biodegradable pins. A biodegradable pin is simply placed onto an ultrasound activated sonic electrode, called a sonotrode, and inserted into the borehole. As a result of the added ultra-sound energy, the thermoplastic biodegradable pin will melt, resulting in a flow of biodegradable polymers into the cortical bone layer and the cavities of the cancellous bone. There is no cellular reaction due to thermal stress during insertion (136). At the same time the biodegradable plate and pinhead fuse. Theoretically, the fusion of plate and pinhead will result into superior mechanical device characteristics in comparison with conventional biodegradable osteofixation systems. This has been claimed as a second advantage. The mechanical strength and stiffness of 7 biodegradable as well as 2 titanium osteofixation systems have recently been investigated (135). One of these investigated biodegradable systems is the Resorb X biodegradable osteofixation system. The SonicWeld Rx and the Resorb X biodegradable osteofixation systems are made of the same co-polymer compositions and have the same device dimensions. These systems are supplied by the same manufacturer (Gebrüder Martin GmbH & Co. (Tuttlingen, Germany )). The question arises to what extent the biodegradable ultra-sound activated SonicWeld Rx osteofixation system presents superior mechanical strength and stiffness as compared with the conventional biodegradable Resorb X osteofixation system. CHAPTER Objectives The objective of this study was to determine the mechanical strength and stiffness of the biodegradable ultra-sound activated SonicWeld Rx osteofixation system in comparison with the conventional biodegradable Resorb X osteofixation system

36 MATERIALS AND METHODS Figure 1. Tensile test set-up CHAPTER The specimens to be investigated were 2 commercially available biodegradable osteofixation systems (i.e. 2.1 mm Resorb X and 2.1 mm ultra-sound activated SonicWeld Rx). All the specimens consisted of biodegradable amorphous poly-(50%d, 50%L) - Lactide. The plates under investigation were 4-hole extended plates. The manufacturer (Gebrüder Martin GmbH & Co., Tuttlingen, Germany) supplied sterile implants. The general characteristics of the included plates and screws are summarized in table II. Eighteen plates and 72 screws/pins of each system were available to perform three different mechanical tests. The osteofixation plates and screws were fixed in 2 different ways to 2 polymethylmethacrylate (PMMA) blocks (with polished surface) that simulated bone segments. For the Resorb X osteofixation system, the screws were inserted in both PMMA blocks according to the prescriptions of the manufacturer (using prescribed burs and taps). The applied torque for inserting the screws was measured to check whether it was comparable to the clinically applied torque ( hand tight ) defined in a previous study (130). For the SonicWeld Rx system, the biodegradable pins were inserted into the boreholes (after the use of prescribed burs) with the sonotrode. The biodegradable polymers melted due to the ultra-sound vibrations of the sonotrode. Subsequently, the biodegradable material flowed into the borehole and the pinhead fused with the biodegradable plate. In both situations, the boreholes were irrigated with saline before insertion of the screws/pins to simulate the in situ lubrication. The two PMMA blocks, linked by the osteofixation device (1 plate and 4 screws/pins) were stored in a water tank containing water of 37.2 degrees Celsius for 24 hours to simulate the relaxation of biodegradable screws/pins at body temperature (111). The tests were performed in another tank containing water at the same temperature to simulate physiological conditions. The use of saline was omitted because of the associated corrosion problems of the test set-up. Omitting the use of saline was expected not to be of influence to the test results. The plates and screws/pins were subjected to tensile, side bending, and torsion tests. The tensile test was performed as a standard loading test (figure 1). Side bending tests were performed to simulate an in vivo bi-lateral sagittal split osteotomy (BSSO) situation (figure 2). Torsion tests were performed to subject the osteofixation devices to high torque in order to simulate the most unfavourable situation (figure 3). The 2 PMMA blocks, linked by the osteofixation device, were mounted in a test machine (Zwick/Roell TC-FR2, 5TS. D09, 2.5kN test machine. Force accuracy 0.2%, positioning accuracy mm; Zwick/ Roell Nederland, Venlo, The Netherlands). Regarding the tensile tests, the 2 PMMA blocks, and thus the osteofixation plate, were subjected to a tensile force with a constant speed of 5 mm/min until fracture occurred (according to the standard ASTM D638M). For the side bending test the 2 PMMA blocks were supported at their ends whereas the plates were loaded in the centre of the construction with a constant speed of 30 mm/min (with this speed the outer fibers were loaded as fast as the fibers of the osteofixation system in Figure 2. Side bending test set-up CHAPTER