Mr. E.M. Emmanuel CHIEF EXECUTIVE. Dr. J C Rhodes PhD MRSC C.Chem MICROBIOLOGIST

Transcription

1 PROJECT : CRANIO-FIX AUTHOR: Mr. E.M. Emmanuel CHIEF EXECUTIVE MODERATOR: Dr. J C Rhodes PhD MRSC C.Chem MICROBIOLOGIST DATE: July 2007

2 CONTENTS Product Rationale Development Rationale Development Prognosis Independent Comparative Test Report Clinical Test Reports Bibliography and Reference Documents

3 CRANIO-FIX RATIONALE The cranioplasty market has been dominated for many years by the Codman preparation launched over 15 years ago. This product has been in continuous use all over the world and is considered the predicate for these types of PMMA cements. Even though there is hardly any published material available on the safety and efficecy of these cements used in cranioplasty procedures, the mere fact that a leading company like Depuy J & J has exploited this product in the market for many years, is evidence that this preparation, when used under the appropriate conditions, provides for a viable and safe surgical solution. All of the clinical references and publications available on most reference sites refer almost exclusively to Hydroxyapetite cement preparations used in cranioplasty. However, we believe that there is sufficient industry and accredited evidence to suggest that HA based cements do not set or harden properly when they come into contact with craniol fluids. Therefore, we have chosen to follow the route of our predicate device supplied by J & J, i.e. a PMMA based cement: Cranioplasty * * Cranioplasty is a registered trademark of J & J

4 DEVELOPMENT RATIONALE 1 Create a modern bone cement using the latest breed of polymers and activators 2 Create a compound that uses significantly less monomer than previous products including the Codman predicate 3 Build in radiopacity 4 Reduce the curing and hardening time to around 8 to 10 minutes 5 Maintain and stabilise working temperatures at around 70 c 6 Create a compound that is easy to manipulate and resists clinging to gloves during the forming process DEVELOPMENT PROGNOSIS Our final product has successfully met all our design criteria

5 BONE-FIX & CRANIO-FIX REPORT STUDY With the CMW and SIMPLEX

6 REPORT STUDY AIM OF THE STUDY: COMPARATIVE STUDY OF FIVE ACRYLIC BONE CEMENTS CMW 1 / BONE-FIX 1/CRANIO-FIX 1 AND SIMPLEX P / CMW 3 / BONE-FIX 3 ACCORDING TO ISO 5833 (1992). PERFORMED BY: C. LAVERGNE The mechanical tests were performed by an external laboratory : "LABORATOIRE DES MATERIAUX - Physico-chimie des phosphates 38, rue des 36 ponts, TOULOUSE" CONFIDENTIAL

7 I - AIM OF THE STUDY Comparative study of two standard viscosity bone cements CMW l and BONE-FIX 1/CRANIO-FIX 1 and three low viscosity bone cements SIMPLEX P, CMW 3 and BONE-FIX 3 with the following tests: Measure of setting time Measure of doughing time Measure of intrusion Compressive strength Flexural strength and flexural modulus These tests are performed according to ISO 5833 (1992). II RESULTS A) BONE-FIX 1 & CRANIO-FIX 1 bone cement Product reference : T Batch number: Cl/9808 The average setting time of two units is 6.1 min. (cf. results in Annexe 1). The average height of intrusion of one unit is 3,97 mm (cf. results in Annexe 2). The average doughing time of two units is lmin. and 37s (cf. results in Annexe 3). The average compressive strength of two units (10 cylinders) is 95.9 MPa (cf. results in Annexe 4) The average flexural modulus and strength of two units (12 samples) are respectively 2633MPa and 57.SMPa (cf. results in Annexe 5). B) CMW 1 bone cement Batch numbers: W106R et W025R The average setting time of two units is 8.6 min. (cf. results in Annexe 1). The average height of intrusion of one unit is 5.0 mm (cf. results in Annexe 2). The average doughing time of two units is 2min. and 47s (cf. results in Annexe 3). The average compressive strength of two units (10 cylinders) is 95.8 MPa (cf. results in Annexe 4) The average flexural modulus and strength of two units (12 samples) are respectively 2243 MPa and 51MPa (cf. results in Annexe 5).

8 C) BONE-FIX 3 bone cement Product reference: T Batch number: C3 / 9901 The average setting time of two units is 8.0 min. (cf. results in Annexe 6). The average height of intrusion of one unit is 6.1 mm (cf. results in Annexe 7). The average doughing time of two units is 5min. and 36s (cf. results in Annexe 8). The average compressive strength of two units (10 cylinders) is 116 MPa (cf. results in Annexe 9) The average flexural modulus and strength of two units (12 samples) are respectively 2665 MPa and 58 MPa (cf. results in Annexe 10). D) CMW 3 bone cement Batch numbers: Y054L-40 et T031L The average setting time of two units is 9.6 min. (cf. results in Annexe 6). The average height of intrusion of one unit is 8.23 mm (cf. results in Annexe 7). The average doughing time of two units is 3min. and 39s (cf. results in Annexe 8). The average compressive strength of two units (10 cylinders) is MPa (cf. results in Annexe 9) The average flexural modulus and strength of two units (12 samples) are respectively 2644 MPa and 62 MPa (cf. results in Annexe 10). E) SIMPLEX P bone cement Product reference : Batch number: CBFO25 The average setting time of two units is 11.7 min. (cf. results in Annexe 6). The average height of intrusion of one unit is 3.98 mm (cf. results in Annexe 7). The average doughing time of two units is 4min. and SSs (cf. results in Annexe 8). The average compressive strength of two units (10 cylinders) is 94.3 MPa (cf. results in Annexe 9) The average flexural modulus and strength of two units (12 samples) are respectively MPa and MPa (cf. results in Annexe 10).

9 Annexe 1 : MEASURE OF SETTING TIME STANDARD VISCOSITY BONE CEMENTS PRODUCTS: BONE-FIX 1/CRANIO-FIX 1 and CMW 1 bone cements BATCH NUMBER: BONE-FIX 1/CRANIO-FIX 1 : C1/9808 CMW 1 : W025R STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± I 'C Cf. following curves SAMPLE CMW 1 Setting time (min.) BONE-FIX 1/CRANIO-FIX 1 Setting time (min.) Average CMW 1 / BONE-FIX 1 / CRANIO-FIX 1 Setting Times

10 Annexe 2 : MEASURE OF INTRUSION STANDARD VISCOSITY BONE CEMENTS PRODUCTS: BONE-FIX 1 / CRANIO-FIX 1 and CMW 1 bone cements BATCH NUMBER: BONE-FIX 1 / CRANIO-FIX 1 : C1/9808 CMW 1 : W025R STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± 1 C SAMPLE CMW 1 Average of four holes mm BONE-FIX 1 / CRANIO-FIX 1 Average of four holes mm Average Intrusion (mm) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1

11 Annexe 3 : MEASURE OF DOUGHING TIME STANDARD VISCOSITY BONE CEMENTS PRODUCTS: BONE-FIX 1 / CRANIO-FIX 1 and CMW 1 bone cements BATCH NUMBER: BONE-FIX 1 / CRANIO-FIX 1 : C1/9808 CMW 1 : W025R STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± 1ºC SAMPLE CMW 1 Doughing time (min.) BONE-FIX 1 / CRANIO-FIX 1 Doughing time (min.) 1 2 min min min min. 30 Average 2 min min. 37

12 Annexe 4 : COMPRESSIVE STRENGTH STANDARD VISCOSITY BONE CEMENTS PRODUCTS: BATCH NUMBER: BONE-FIX 1 /CRANIO-FIX 1 and CMW 1 bone cements BONE-FIX 1 /CRANIO-FIX 1 : Cl/9808 CMW 1 : W 106R STANDARD REFERENCE: ISO 5833 (1992) TEST SPECIMENS: CYLINDERS Height: 12.0 mm Diameter: 6.0 mm RESULTS: Ambient temperature: 23 ± 1 C CMW 1 BONE-FIX 1 / CRANIO-FIX 1 SAMPLE Compressive strength Compressive strength ơ (MPa.) ơ (MPa.) Test 1 Test 2 Test 1 Test Average 97.9 ±4 93.8±2 90.5± ±2 Average of two units Compressive strength(mpa) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1

13 Annexe 5 : FLEXURAL STRENGTH AND MODULUS STANDARD VISCOSITY BONE CEMENTS PRODUCTS: BATCH NUMBER: BONE-FIX 1 /CRANIO-FIX 1 and CMW 1 bone cements BONE-FIX 1 /CRANIO-FIX 1 : C1/9808 CMW 1 : W 106R STANDARD REFERENCE: ISO 5833 (1992) TEST SPECIMENS: Parallelepiped Immersion in water at 37 C ± 1 C for 50h ± 2h Width: 10,0 mm Thickness: 3.3 mm RESULTS: Ambient temperature: 23 ± 1 C CMW 1 BONE-FIX 1 /CRANIO-FIX 1 CMW 1 BONE-FIX 1 /CRANIO-FIX 1 SAMPLE Flexural strength Flexural strength Flexural modulus Flexural modulus B (MPa.) B (MPa.) E (MPa.) E (MPa.) Test 1 Test 2 Test 1 Test 2 Test 1 Test 2 Test 1 Test Average 52.0± ± ±4 58.1± ± ± ± ±113 Average of units Flexural strength (MPa) Flexural modulus (MPa) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1 CRANIO-FIX 1

14 Annexe 6 : MEASURE OF SETTING TIME LOW VISCOSITY BONE CEMENTS PRODUCTS: BATCH NUMBER: SIMPLEX P, BONE-FIX 3 and CMW 3 bone cements SIMPLEX P : CBF025 BONE-FIX 3 : C3/9901 CMW 3 : Y054L-40 STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± 1ºC Cf. following curves SAMPLE SIMPLEX P Setting time (min.) CMW 3 Setting time (min.) BONE-FIX 3 Setting time (min.) Average CMW3 / SIMPLEX P / BONE-FIX 3 setting times

15 Annexe 7 : MEASURE OF INTRUSION LOW VISCOSITY BONE CEMENTS PRODUCTS: SIMPLEX P, BONE-FIX 3 and CMW 3 bone cements BATCH NUMBER: SIMPLEX P : CBF025 BONE-FIX 3 : C3/9901 CMW 3 : Y054L-40 STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± 1ºC SAMPLE SIMPLEX P CMW 3 BONE-FIX 3 Average of four holes Average of four holes Average of four holes (mm) (mm) (mm) Average Intrusion (mm) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1

16 Annexe 8 : MEASURE OF DOUGHING TIME LOW VISCOSITY BONE CEMENTS PRODUCTS: SIMPLEX P, BONE-FIX 3 and CMW 3 bone cements BATCH NUMBERS: SIMPLEX P : CBF025 BONE-FIX 3 : C3/9901 CMW 3 : Y054L-40 STANDARD REFERENCE: ISO 5833 (1992) RESULTS: Ambient temperature: 23 ± 1 C SAMPLE SIMPLEX P Doughing time (min.) CMW 3 Doughing time (min.) BONE-FIX 3 Doughing time (min.) 1 5 min. 3 min. 42s 5 min. 52s 2 4min. 49s 3 min. 36s 5 min. 20s Average 4min. 55s 3 min. 39s 5 min. 36s

17 Annexe 9 : COMPRESSIVE STRENGTH LOW VISCOSITY BONE CEMENTS PRODUCTS: BATCH NUMBERS: SIMPLEX P, BONE-FIX 3 and CMW 3 bone cements SIMPLEX P : CBF025 BONE-FIX 3 : C3/9901 CMW 3 : T031L STANDARD REFERENCE: ISO 5833 (1992) TEST SPECIMENS: CYLINDERS Height: 12,0 mm Diameter: 6.0 mm RESULTS: Ambient temperature: 23 ± 1 C SIMPLEX P CMW 3 BONE-FIX 3 SAMPLE Compressive strength Compressive strength Compressive strength ơ (MPa.) ơ (MPa.) ơ (MPa.) Essai 1 Essai 2 Essai 1 Essai 2 Essai 1 Essai Average 92.4±4 96.3± ± ± ± ±2 Average of 2 units Compressive strength (MPa) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1

18 Annexe 10: FLEXURAL STRENGTH AND MODULUS LOW VISCOSITY BONE CEMENTS PRODUCTS: BATCH NUMBERS: SIMPLEX P, BONE-FIX 3 and CMW 3 bone cements SIMPLEX P : CBF025 BONE-FIX 3 : C3/9901 CMW 3 : T031L STANDARD REFERENCE: ISO 5833 (1992) TEST SPECIMENS: Parallelepiped Immersion in water at 37 C ± 1 C for 50h ± 2h Width: 10.0 mm Thickness: 3.3 mm RESULTS: Ambient temperature: 23 ± 1ºC SIMPLEX P CMW 3 CEMFIX 3 SIMPLEX P CMW 3 BONE-FIX 3 SAMPLE Flexural Flexural Flexural Flexural Flexural Flexural strength strength strength modulus modulus modulus B (MPa.) B MPa. B MPa. E (MPa.) E MPa. E MPa. Essai 1 Essai 2 Essai 1 Essai 2 Essai 1 Essai 2 Essai 1 Essai 2 Essai 1 Essai 2 Essai 1 Essai Average 63.4 ± 60.6 ± 58.9 ± 56.3 ± ± 136 ± 124 ± 246 ± 195 Average of 2 units Flexural strength (MPa) Flexural modulus (MPa) ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 ISO 5833 BONE-FIX 1/ CMW 1 SIMPLEX P BONE-FIX 3 CMW 3 CRANIO-FIX 1 CRANIO-FIX 1

19 Clinical experience with specific pmma bone cements Dr F. Furzun/ Jonzac Hospital (France ) Dr N. Sahraoui/ Clinical department (Teknimed - France ) Introduction The aim of this study is to report our comments and experiments on the use of a polymethylmethacrylate surgical cement in prosthetic surgery for fixing of our implants. It is first important to remind that arthroplasty of a cemented hip remains a very effective technique, provided the procedure is well performed. During the last decade, it became obvious than the quality of the cementing technique was more important for the long term result than the implant choice. These modern cementing techniques helped to improve the mechanical interlocking between bone and cement, then creating a strong and tight interface with time. Indeed, a good penetration of the cement into bone trabeculae increases shear strength of the bone-cement interface. Such an cement interpenetration does not only depend on a thorough bone preparation consisting in the preservation of cancellous bone, but also on lavage, injection process and the cement itself. Rates of long-term survival of more than 95% after 10 years are now common. (References 1,2,3) At first, we wanted to know the specifications of these cements and their performances, according to our scientific knowledge on this subject. MATERIAL AND METHOD Materials : Four different types of pmma bone cement were used in this study : a standard viscosity cement and low viscosity one with or without antibiotics. The choice of the cement to implant was made according to the indications and the surgeon practices. From the surgical practice and requirements set up in our department, we have chosen bone cements manufactured for Implants International by Teknimed BONE-FIX, CRANIO-FIX and BONE-FIX with Gentamicin (BONE-FIX G) because of their physicochemical performances and pharmaco - kinetics. On the physico-chemical level: From our surgical practice and the requirements, that we set up for ourselves in our service, we chose cements manufactured for Implants International by Teknimed, for their physico-chemical properties. The powder / liquid ratio of these cements is higher than 2, 2.5 for Bone-Fix 1 / Cranio-Fix 1 and Bone-Fix G 1 and 2.2 for Bone-Fix 3 and Bone-Fix G 3. Such a low ratio induces less release of monomer, a lower exotherm, then reducing cardiovascular risks for the patient. The mechanical characteristics of these cements necessary for an optimal use meet the requirements of the ISO On the Pharmacokinetic level: These cements were also chosen because of their pharmacokinetics as the kinetics release of antibiotic from a bone cement matrix is of great importance in term of efficient local therapy. In general, the local concentration rates must be higher than the CMI (minimal inhibitory concentration) of the encountered species. All the antibiotics are not well adapted to a local therapy with pmma bone cements. To obtain an effective antibiotic treatment, the chosen cement must show a first flash release in the first hours followed by a progressive and controlled release the days or weeks after. Moreover, the antibacterial spectrum must be broad, including g gram(+) and gram(-) bacteria with a bactericidal effect even for low concentrations. Two antibiotic bone cements containing 1g of gentamycin base were selected from these requirements.

20 On the practical level: On a practical point of view, theses cements have a very short waiting phase that allows a rapid implantation and then a longer working phase. The kinetics of viscosity also allows an homogeneous mixture together with a good handling. Depending on the indication, low viscosity Bone-Fix 3 and Bone-Fix G 3 were implanted with a syringe, thus enabling a better filling of the cavity of the hip or the shoulder. In the Case of knee replacement procedure, more viscous cements such as Bone-Fix 1/Cranio-Fix 1 and Bone-Fix G 1 were used. Cementing-Technique The cementing technique used was the same for all cases, consisting in an abundant lavage of the intramedullary canal in order to remove any bone or marrow particles and debris. Osseous lavage is indeed mandatory for a good bone-cement interface and for reduced risks of embolism. After lavage, thorough bone preparation, introduction of an intramedullary, the cement was introduced under pressure in order to induce greater cement penetration. A good cancellous structure was preserved in order to support cement interpenetration. (Fig. I / Fig 2). Once the stem had been put No definitively in place, the excess cement was withdrawn. The longevity of a cotyle implant is partly induced by its wear resistance. This is why the bone-cement-implant interface has to be as solid and tight as possible. And this can be obtained by a solid initial fixation of the implant BONE-FIX 1 / CRANIO-FIX 1 Fig 1 Fig 2 Number of cases: The investigation concerned three center hospitals : center hospital of Jonzac, center hospital Tarbes and center hospital of Saintes. This work is a retrospective study from 1999 to 2006 on 325 patients: 219 women and 106 men, of 68 years average age (65 years - 82 years). They were divided as follow : cemented total hip prostheses after a primitive coxarthrosis, 50 intermediate hip prostheses after femoral neck fractures, with a total of 62 hip prostheses, (42 right sides and 20 left sides) total arthroplasty revisions - 38 shoulder prostheses indicated for humeral upper extremity fractures into 4 l1ragments total knee prostheses for advanced arthrosis. - 1 knee arthrodesis, after an infected knee prosthesis failure A systematic clinical examination was performed for each patient In each center, the patients were operated by the same surgeon and using the same technique. All patients were re-examined after operation with a radiological follow up in order to follow the evolution. The average follow up was 7 years.

21 RESULTS It's well known that pmma bone cements are effective for long term prosthesis fixation Since their first uses, many reports have shown the efficacy of this biomaterial. As clearly shown in this study, a good preparation and cementing technique are the key parameters for good long term survival of cemented prosthesis. None per-operatory incident or loosening were reported among the 325 cases. It is clear that these pmma bone cements gave entirely satisfaction to the surgeon for the primary implant stabilisation. They perfectly accomplished their goal of a stable and solid implant fixation. Clinical Case No 1 66 year old Woman, operated for a left coxarthrose in July 2003, a cemented total prosthesis was indicated. Before surgery BONE-FIX 1 / CRANIO-FIX 1 BONE-FIX 3 1 year follow up

22 Clinical case No. 2 A 78 years old patient operated on its left hip for coxarthrose radiological Results at 3 years of a total prosthesis of hip cemented with of Bone-Fix G 3 for the femoral stem mid with of Bone-Fix G 1 for cotyle. Follow up Radiograph of this case: to note the quality of cementing, as well as the homogeneity of the cement coat in the 2 plans with the respect of the same technique. BONE-FIX G 1 BONE-FIX G 1 BONE-FIX G 3 BONE-FIX G 3

23 Clinical case No 3 A 68 years old patient operated for a neck femoral fracture. Implantation of an intermediate hip prosthesis with fixation of femoral stem with Bone-Fix 3. A regular thickness of the coat of cement from 2 to 5 mm must be done, especially in middle and anterior area. Pre-operatory Pre-operatory BONE-FIX 3 4 years

24 Clinical case No 4 A 70 years old patient operated for a revision hip prosthesis Pre-operatory post-op immediate 1 year post-op 6 years post-op

25 Clinical case No 5 Arthrodesis of the knee with a special implant, "Bibloc" In this case Bone-Fix G 1 was used as a spacer during 45 days, to treat an infection after removing an infected knee prosthesis Bone-Fix G 1 The biology after the treatment was normal, without sign of infection Post-op immediate 2 years follow up 6 years follow up No infection's resumption, the site was completely sterilisade, the biology after the treatment stay normal, the follow up today is 6 years.

26 Clinical case No 6 A 70 years old patient operated for a gonarthrosis of the left knee. The total knee prosthesis was implanted with Bone-Fix G 1. Before surgery BONE-FIX G 1 1 year post-opratory

27 Clinical Case No 7 A 75 years old patient operated for a gonarthrose of its left knee. Implantation of a total knee prosthesis with Bone-Fix G 1 Pre-operatory Pre-operatory 1 year

28 Clinical Case No 8 Here the case of a 65 year old patient having an humeral fracture of upper extremity for which an indication of total shoulder prosthesis was done. Before surgery CT scan showing the complete separation of the humeral head Shoulder prosthesis implanted with Bone-Fix 1/Cranio-Fix 1 2 years follow up

29 Clinical case No 9 Here the file of a 65 year old patient with a Pace maker, who has an humeral fracture with 4 fragments of the higher extremity. An indication of shoulder prosthesis cemented with Bone-Fix G 1 was done. BONE-FIX G 1

30 Clinical case No years old schizophrenic patient, who presented an humeral fracture with 4 fragments of the higher extremity. Before surgery Surgery BONE-FIX 1 / CRANIO-FIX Post surgery radiographics of cemented shoulder prosthesis fixed with Bone-Fix l / Cranio-Fix 1

31 Conclusion It's well know that the pmma bone cements are effective for long term prosthesis fixation Since the first uses, many reports have shown the fiability of this biomaterial. As clearly shown in this study, a good preparation and cementing technique are the key parameters for good longevity of cemented prostheses. None incident per-operatory or loosening are reported. It's clear that this biomaterial gave entirely satisfaction to the surgeon to the fixation of the implants. They accomplished their goal of fixation and a solid, stable and durable embading of implants. 1 - Askew M3, Steege JW, Lewis 3L, Ranieri JR, Wixson RL. Effect of cement pressure and bone strength on polymethylmethacrylate fixation. 3 Orthop Res 1984; 1: Breusch S3, Lukoschek M, Kreutzer 3, Brocai DRC, Gruen T. Dependency of cement mantle thickness on stem design and centralizer. J Arthroplasty 16/5 (2001), 16(5): Ebrarnzadeh EE, Sarmiento A, McKellop HA, LLinas A, Gogan W. The cement mantle in total hip arthroplasty. Analysis of long-term radiographic results. J Bone Jo

32 Bibliography Comparative analysis of clinical outcome between the use of porous polyethylene implant and traditional PMMA cement. (J Korean Neurosurg Soc 38:96-101, 2005) Experimental evaluation of a percutaneous injectable biomaterial used in bone-filling procedures. (Journal of Materials Science ISSN ) Comparative analysis of clinical outcome in cranioplasty using poly mesh vs PMMA cement. (Neurosurg Focus 16 March 2004) Clinical outcome in cranioplasty using bone autograft and alloplasts. (J Craniofacial Surg Sept Michigan USA) Cranioplasty Clinical outcomes and follow up using calcium phosphate cements. (The Internet Journal of Plastic Surgery ISSN )

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