FINITE ELEMENT MODELING OF BONE BY USING HYDROXYAPATITE AS BIOACTIVE NANOMATERIAL IN BONE GRAFTING, BONE HEALING AND THE REDUCTION OF
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1 CHAPTER-IV FINITE ELEMENT MODELING OF BONE BY USING HYDROXYAPATITE AS BIOACTIVE NANOMATERIAL IN BONE GRAFTING, BONE HEALING AND THE REDUCTION OF MECHANICAL FAILURE IN THE BONE SURGERY This Chapter communicated to International Conference on Nanoscience, Technology & Societal Implications NSTSI11 during Dec 8-10,2011
2 Chapter 4 FINITE ELEMENT MODELING OF BONE BY USING HYDROXYAPATITE AS BIOACTIVE NANOMATERIAL IN BONE GRAFTING, BONE HEALING AND THE REDUCTION OF MECHANICAL FAILURE IN THE BONE SURGERY 4.1. INTRODUCTION The ability to design nanomaterials on the nanometer scale would create amazing functional properties like superior surface reactivity with surrounding tissues favorable for human health care applications. Nano biomaterials can be either single phase or multiphase components. Single phase biomaterials are homogeneous, where as multiphase biomaterials are heterogeneous. The term multiphase, or composite refers to a combination of at least two different phases of materials. Micro scale composite materials are good candidates for a given function; however, composite materials designed at the nano scale level have gained much recognition in almost all fields, in particular bone related therapy. The driving force behind the development of nano composites is primarily related to superior surface properties, high degree of mono dispersity, reproducibility, and close surface contact with surrounding tissues, owing to the large surface area with adequate physical, chemical and biological properties. These unique nano features render the materials ideal for a wide variety of biomedical applications. The term nano composite represents a heterogeneous combination of two or more materials, in which at least one of the materials should be on the order of nano scale dimension. Many types of nano composite materials are already in use and some are under investigation as bio-implants in bone grafting and tissue engineering applications. A three-dimensional FEM of the bone with geometrical personalization was use. Then, main characteristics of degenerative pathologies and surgical gestures were considered, and posterior implants were modeled.
3 4.2. BONE GRAFTING Bone as a Tissue Bone is a specialized form of dynamic biological hard tissue forming the skeleton of the body. It is composed primarily of organic collagen fibrils impregnated with inorganic calcium phosphate- based minerals in conjugation with metabolically active cellular components. The collagen acts as a structural frame work in which plate-like nanocrystals of hydroxyl carbonate apatite are embedded to strengthen the bone [52,55] the diameter of the collagen fibers varies from 100 to 2000nm. The HA crystals are needle like and 40 to 60 nm in length, 20 nm in width, and 1.5 to 5nm in thickness [20,46]. The calcium phosphate-based nanocrystals are arranged in layers that traverse the organic collagen fibrils [33,78]. The overall composition of bone tissue is shown in table 4.1 according to its approximate weight ratio [52]. In addition to bone minerals and collagenous proteiens, bone is enriched with four types of cells, namely, osteprogenitor cells, osteoblasts, osteocytes, and osteoclasts [12]. Table 4.1. COMPOSITION OF BONE Inorganic phase (Wt %) Organic phase (Wt %) Hydroxyapatite ~ Collagen ~ 20 Carbonate ~ 4 8 Water ~ 9
4 Citrate ~ 0.9 Other trace elements: Sodium ~ 0.7 Noncollagenous proteins, Magnesium ~ 0.5 and Polysaccharides, and lipids Trace elements of Cl -, F -, and K Bone-Healing Mechanism The bone-healing process restores defective tissue to its original physical, mechanical, biochemical, and biological functions and is influenced by a variety of systemic and local factors. Bone healing occurs in three distinct but overlapping stages, namely, inflammatory stage, repair stage, and remodeling stage. In the early inflammatory, a hematoma progresses within the bone fracture site during the first few hours to days. Inflammatory bone cells and fibroblasts infiltrate the bone under prostaglandin mediation and this result in the formation of granulation tissue, in-growth of vascular tissue, and migration of mesenchymal cells. The primary nutrient and oxygen supply during this early process is provided by the exposed cancellous bone and muscle. The use of anty-inflammatory or cytotoxis medication may alter the inflammatory responses and inhibit bone healing during first week. In the repair stage, fibroblasts begin to lay down a stroma that helps to support vascular in-growth. Once vascular in growth begins, an organic collagen matrix is laid down while osteoid is secreted and subsequently remineralized; this leads to the formation of callus around the fracture surface. This callus is very weak during the first 4 to 6 weeks of the healing process and requires sufficient protection in the form of bracing or internal fixation. Ultimately, the callus ossifies and hence forms a bridge of woven bone between the fracture fragments. Alternatively, in the absence of proper immobilization, ossification of the callus may not occur, possibly resulting in an unstable fibrous union. Complete fracture healing occurs only
5 in the bone remodeling stage, in which the healing bone is restored to its original shape, structure, and strength. Remodeling of the takes place slowly over months to year; the rate of modeling dependent upon several factors including age, nutrients, and complication of defects, and is facilitated by mechanical stress placed on the bone. As the fracture site is exposed to an axial loading force, bone is generally laid down where it is needed and resorbed from where it is needed. Adequate bone strength is normally achieved in 3 to 6 months. Thus special care during the bone healing period is required to stimulate faster healing in a natural way Need for Bone Grafting Bone is one of the few tissues capable of self-regeneration during skeletal deficiency, but this regeneration is limited to the nature and size of the defect. In general, skeletal deficiency occurs as a result of trauma, tumor, bone disease, or abnormality. Surgical treatment is required to restore normal bone function. For example, if a minor fracture occurs, usually bone is capable of restoring function in a few weeks. In case of severe fracture, bone will not heal by itself. For this, an artificial bone grafting substitute may be required to restore routine function without damaging living tissue. Selection of bone graft substitutes is the most important criterion for better performances in vivo. Bone graft substitutes should be highly biocompatible, bioactive, nontoxic (should not damage surrounding living tissue), noncarcinogenic, nonimflamatory, and should not elicit any immunologic responses. Finite Element Method (FEM) is useful to analyze mechanical behavior of human body structures. Several authors have investigated the mechanical behavior of intact, injured and instrumented vertebral segments using finite element models. Some of these studies proposed a combined approach using in vitro experiments and FEM, parameterization of the spine geometry allowed analyzing the effects of geometrical parameters on the mechanical
6 behavior [15] however regarding spinal implants, evaluation only considered standard bone which is not accurate enough to develop a predictive tool based on FEM. The aim of this study is to provide a patient specific finite element model of the lumbar spine where surgical gesture was considered and to assess its relevance as a predictive tool for lumbar spine surgery Bone Grafting Techniques Bone grafting is a technique used in orthopaedic surgery. It is a surgical procedure used to repair or replace lost bone with the aid of a bone graft substitute. With the application of this technique, bone healing time is reduced and new bone formation strengthens the implanted area by bridging existing bone to the grafted substitute. Bone grafting techniques can be categorized into four types corresponding to grafting terminology and the implant material used. These are autograft, allograft, xenograft, and alloplastic graft Synthetic Biomaterials as Bone Grafts Recent advances in science and technology have markedly increased the success of synthetic biomaterials as bone graft substitutes as a viable alternative to the traditional autografts and allografts. This kind of biomaterial has been developed for bone substitution for the past 3 decades and has been used effectively clinically [4,29,34]. The materials commonly used as bone substitutes are typical metals, ceramics, polymers, and their composites. Metals and ceramics are primarily for hard tissue applications, and typically polymers are used for soft tissue applications, owing to their structural and mechanical properties. Among the biomaterials, bioactive HA and its composites play a key role in producing artificial bone graft substitutes [41,42]. The development of bioactive materials engineered at the nano level with surface properties similar to those of physiologic bone would undoubtedly facilitate rapid new bone formation at the biomaterial-tissue interface
7 [30]. Nanostructured biomaterials are a generous gift, either as temporary or permanent substitutes for defective or degenerated tissues and organs [43]. They could be a breakthrough in human health care applications, including rejuvenation of bone grafts. It is also possible to synthesize nanocomposite biomaterials for orthopaedic applications with the help of nanotechnology, in order to mimic the natural bone tissue Role of nano hydroxyapatite in bone grafting Owing to their nanostructured properties, there is an increasing demand for nanoscale biomaterials to assist in the repair of osseous defects caused by skeletal deficiencies. In this stare, calcium phosphate-based bioceramics, in particular HA, dominate as bone graft substitutes, owing to their structural similarity to natural bone mineral, thereby making them very attractive for use in bone remodeling [2,6,27, 35]. HA is a bioactive ceramic material with the chemical composition. It has been used for over 3 decades in various medical applications. HA is a major inorganic phase of hard tissue such as bone and tooth. Primarily, it is employed in the repair of skeletal defects, owing to its close resemblance to natural bone mineral. The HA derived either synthetically or naturally is regarded as bioactive substance, since it forms a strong chemical bond with hard tissue, and hence it is recognized as a substitute material for damaged teeth or bone in dental and orthopaedic applications. Generally, HA is not only bioactive but also osteoconductive, nontoxive, nonimmunogenic, and its structure is crystallographically similar to that of bone mineral with adequate amount of carbonate substitution [3, 7, 34]. The characteristic properties of HA make it a good candidate for a wide range of biological and industrial applications [14, 23, 24,].
8 Basically, HA is a family of apatite phase. The term apatite was derived from the Greek word and coined by Werner in The term apatite belongs to a family of components having similar structures but not necessarily having identical phase composition [34]. Apatite is a type of calcium phosphate material and it was invented such that it was quite similar to calcined bone tissue in terms of chemical groups, although the role of the OH, F, and Cl was not recognised at the time it was invented. The first synthesis of apatite was carried out by Daubree in 1851; The chemical composition of HA can be written as Ca 4 (I)Ca 6 (II)(PO 4 ) 6 (OH) 2. There is a long history of preparing HA at the micrometer scale in various forms like powder, dense or porous blocks, corresponding to clinical applications [25]. During the past few years, significant research efforts have been devoted to nanostructure processing of HA and its composites in order to obtain an ultra-fine structure with physical, chemical, and biological properties similar to those bones of natural bone. Ultra- fine HA has unique advantages over conventional HA, given its increased surface area and ultra-fine structure, which are properties essential for cell substrate interactions upon implantation. With the advance of ceramic and nanotechnology, the potential of nano HA as a bone graft substitute has generated considerable interest, owing to some of its characteristic features including superior biocompatibility, osteoconductivity, bioactivity, and noninflammatory nature (29,30). One of the significant properties attributed to nanomaterials, namely, high surface area reactivity can be exploited to improve the interfaces between cells and implants. In addition, nanocrystalized characteristics have proven to be of superior biological efficiency. For example, compared to conventionally crystallized HA, nanocrystallized HA promotes osteoblast adhesion, differentiation and proliferation, osteointegration, and deposition of calcium-containing minerals on its surface, thereby enhancing the formation of new bone
9 within a short period. Therefore, nanostructured HA is represented as a unique class of bone grafting material MATERIALS AND METHODS Preparation of Nano Hydroxyapatite HA can be prepared by many experimental techniques including solid state, wet chemical, hydrothermal, mechano chemical, and more recently microwave processing (34). Some of the properties of HA can be manipulated slightly with respect to preparation methodology and key ingredients used in the reaction medium. Depending upon the experimental technique HA can be produced with various morphologic characteristics, stoichiometry, and crystalinity. We prepared with microwave processing technique. The nano HA was synthesized by the precipitation method using NH 4 H 2 (PO 4 ) and Ca(NO 3 ) 2.4H 2 O. The precipitate was subjected to microwave sintering after being washed with distilled water with high speed centrifuge. The microwave generated the power conception of 980 W and power output of 490 W with a frequency of 2.45 GHz for a period of 5 to 15 minutes. Prepared HA was characterized by using SEM, TEM, XRD, etc. and used for bone transplantation Patient specific finite element model A fully validated three-dimensional finite element model of the concern bone transplantion using HA is shown in fig.4.1. [54]. For the geometrical personalization of the FEM, a specific algorithm based on a statistical bone model was adapted [32, 50] to obtain the 3 D shape and position of bone. This model takes into account the geometric and material non-linearity. Surface contact elements were considered for the articular facets, and material
10 properties of soft tissues were defined according to published data [63], and then refined in a parameter identification process so that the numerical results fit with those of the LBM database. Posterior implants for osteosynthesis were modeled using beam elements and integrated in the bone FEM. This modeling was fully parameterized to take into account the surgical strategy (material, rod diameter, screws diameter and length.) and the surgical gesture (arthectomy, discetomy). Fig.4.1, Finite Element model of bone transplantation using bio active nanomaterials Advantages of the Method
11 This method offers several advantages they are easily maintain optimum conditions in order minimize reaction time, energy saving and production cost, and to increase the purity of biomaterial. The results indicated that HA ceramics prepared by this method were denser and had fine grain size when compared to conventional heating methods, easy to evaluation of FEM as a predictive tool Changes and Future Directions in Bone Grafting Despite the progress in biomedical science and technology, the need for bone graft is gradually increasing annually, owing to the factors described earlier. Although autogenic and allogenic grafts have excellent track records, often they have limited availability, are antigenic, and are associated with the risk of infectious disease transmission. Hence, the demand for bone graft substitutes is continuing to increase and the quest for ideal graft substitute continues. Improved surgical instrumentation is now allowing reconstructive procedures that will undoubtedly require new graft technology. Consequently, research continues for a superior bone graft substitute and to improve the quality of existing biomaterials. The advancement of nanoscience and nanotechnology combined with materials science paves the way for fabrication of the ideal bone graft substitutes engineered at the molecular level to enhance the quality and length of human life RESULTS AND DISCUSSION Concerning in vitro evaluation of the instrumented model, numerical load displacement curves have been compared to experimental ones for all load cases and for all configurations (intact, instrumented, and injured). The numerical curves presented similar
12 patterns as experimental ones. Numerical ranges of motion were within the experimental corridors and effect of instrumentation and injury were similar to those observed experimentally. The process presented in this study allowed to obtain a 3D reconstruction of the patient bone and then to personalize geometrically a detailed finite element model for a given. The full simulation process is automatic for most of the patients. If only requires manual intervention in case of severe deformation of the bone: high grade of spondylolisthesis or high disc degeneration. With this successfully transplant the bone using HA CONCLUSION Being the first inventor, nature sets high standards for biomaterial scientists and engineers who design medical implants to augment, direct, or replace the functions of living tissues of the human body. The most elusive and preferred goal is to produce artificial biomaterials that mimic functional properties of natural tissues organs in terms of physical, mechanical, chemical, and biological performance. With the aid of nanoscience and nanotechnology, considerable research in bone grafting have provided the opportunity for design of biomaterials engineered at the molecular level with all of the ideal features, in order to function in natural way in the body. In the case of bone grafting, nanocomposites play vital role, as natural bone itself is a composite material consisting of collagen of collagen fibrils embedded with inorganic nanoapatite crystals through nano collageneous proteins. It is anticipated that the bone graft materials engineered at the nanometer level elicit favorable host tissue biomaterial interaction upon implantation. Therefore, novel and innovative approaches are needed to enhance the efficacy of nanoscale biomaterials, which leads to improved quality and length of human life.
13 For the first time a patient specific model was proposed for bone surgery planning. Even if the proportion of clinical cases is unbalance between successes and failure cases, first simulations were promising in the ability of the FE modeling to identify preoperatively the risk of mechanical implant failure for a given patient, with its own geometry, pathology, implant and surgery. Then, by increasing the number of modeled clinical cases, it could be possible to improve this model and to provide this model and to provide a help for surgery planning.
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