BOP: biocompatible osteoconductive polymer: an experimental approach

0267-6605(94)00005-0

Clinical Materials 16 (1994) 217-221 Elsevier Science Limited Printed in Great Britain 0267-6605/94/$7.00

BOP: Biocompatible Osteoconductive Polymer: An Experimental Approacht F. Buren," R. Bourgois," F. Burny.?" C. Chaboteaux," J. d'Hemricourt," S. E1 Banna," J. L. Pasteels," S. Sintzoff" & A. Vienne" Department of Orthopaedics and Traumatology, Cliniques Universitaires de Bruxelles, Hopital Erasme, Brussels, Belgium b Department of Civil Engineering, Ecole Royale Militaire, Brussels, Belgium c Laboratory of Histology, ULB, Faculte de Medecine, Brussels, Belgium d Department of Orthopaedics and Traumatology, Hopital Universitaire Andre Vesale, Charleroi, Belgium e Department of Radiology, Cliniques Universitaires de Bruxelles, Hopital Erasme, Brussels, Belgium

a

Abstract: BOP (biocompatible osteoconductive polymer) is a material proposed for osteosyntheses and for filling of bone defects in orthopaedics, neurosurgery and stomatology. It is a composite made of a copolymer of N-vinylpyrrolidone and methylmethacrylate, of polyamide-6 fibers and of calcium gluconate. The histological investigation includes the study of 30 intact rabbit femurs instrumented with a BOP rod, as well as the study of organs of the reticuloendothelial system. The currently available results show the absence of toxicity on hematopoietic tissue. Zones of osteoblastic activity surround the rods, coupled with an osteoclastic reaction which may result in the partial fragmentation of the polyamide fibers and its incorporation in the newly formed bone. We also observed the encapsulation of the material. The biomechanical approach investigated the mechanical properties of the material in bending and in shear. The radiological aspects of the investigation consisted of computerized axial tomography of the implanted femurs to measure density at the bone-implant interface.

INTRODUCTION

polyamide-6 fibers which account for 50% of the composition; the matrix (40%) is a copolymer of vinylpyrrolidone and methylmethacrylate; the last 10% is made up by calcium gluconate' Several presentations of this material are now available:

BOP (biocompatible osteoconductive polymer) was developed and used in the USSR in the 1970s. The material was used in traumatology and orthopaedics for procedures such as osteosyntheses (femur, tibia, fibular, forearm), coverage of the acetabulum and filling of defects after tumor resection.' It was used later in western Europe with other indications' and in Mexico. 3,4 Several formulae were tested in vitro before achieving the actual composition of the material. It is composed of

-malleable paste (cranioplasty) -powder (to fill small defects); -chips and fibers (filling of greater defects, ligamentoplasty); -blocks used in neurosurgical and orthopaedic procedures. A potential application for the rods is, for instance, the repair of malleolar fractures. At the present time, BOP is mostly used in neurosurgery for intercorporeal arthrodeses of the cervical

t Paper presented at the European Materials Research Society in 1992. * To whom correspondence should be addressed. 217

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F. Buran et al.

Fig. 1. The polyamide-6 fibers under polarized light, transverse section at 6 weeks.

spine 2,6,7 and pinning of the dens of the axis." It is also used as a bone graft complement in arthrodeses of the spine (thoracic and lumbar)," and in cranioplasty. 10,11 In orthopaedics, a series of acetabular augmentation using BOP paste and a series of revisions of hip arthroplasty using BOP fibers as filler have been published.l/ The powder is used in dentistry and in stomatology.13,14 Some authors have developed a new surgical procedure to treat hip dysplasia in dogs; this procedure requires BOP blocks and fibers. 15,16 Toxicology studies on BOP are reportedY-19 However, to our best knowledge, few systematic histological works have been published.i" The purpose of this study is to investigate the interactions between the bone and the BOP. We present preliminary results, only part of the animals have been examined to-date. MATERIALS AND METHODS

Animal experimentation New Zealand rabbits (3-4 kgs in weight) were used. Both femurs of each animal were implanted, under general anesthesia. A small incision was made, centered on the great trochanter, and continued between the muscles to expose the entry point of the rod in the femur. A 3.5 x 40 mm intramedullary rod was inserted, using special instrumentation, as recommended by Hobkirk.i' The rabbits recovered in their cages after surgery, and remained without ambulatory restriction.

Histology Three animals were sacrificed after each period of implantation: at 4 weeks, 8 weeks, 4 months, 8 months, and 1 year. The two femurs, the kidneys, the liver, the lungs, the spleen and some of the aortic lymph nodes were removed. The samples of hard tissue (bone and BOP) were embedded in methacrylate, cut and stained before observation.P'" It is extremely difficult to prepare such histological specimens without introducing artefacts between zones of different hardness and within the composite material. Additionally, the polymeric matrix probably disappears during fixation, dehydration and embedding of the material. On the other hand a great advantage of this material for histological study is the birefringent property of the fibers (Fig. 1), which allows small fragments of the material to be easily localized in the tissues as reported by Bostmarr'" for other materials.

Radiology The radiological approach consisted of the measurement of the density at the bone-implant interface. The technical conditions of the measurements were: CT Scan Somatom plus, 120 kV, 165 mAmp, 1 mm thickness and 2s acquisition time. Transverse sections of the implanted rabbit femurs were observed and the values of the radiological density measured in a standardized zone of the

Biocompatible osteo conductive polymer

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Fig. 2. Fragments of polyamide fiber in an osteoclast (arrow) after I year on the border of the medullary cavity . Semi polarized light.

bone. The densities were measured along a transversal axis and represented graphically; reconstruction algorithms were selected to improve the resolution in density.

Biomechanics We investigated the bending and shear characteristics of BOP octogonal rods, with a nominal diameter of3.5 mm and a length of 90 mm. A universal testing machine (Tinius Olsen) and an Orion Schlumberger data logger were used. The tests were performed under the conditions described in the Euronorm EN-62: 24 h conditioning at 23 ± 2°C and 55 ± 5% relative humidity. A three point bending test was performed in accordance with the procedure B-method I of the ASTM D790M-81,28 except that the cross-section was octogonal instead of rectangular; the distance between the supports equaled 10 times the inner diameter of the rod. Afterwards two double shear tests were performed on the extremities.

RESULTS Histology At 4 weeks, a foreign body reaction was observed around the implanted material in contact with the bone, together with an osteoblastic reaction and the formation of a pseudoepithelial arrangement of the osteoblasts. This reaction was coupled with

the activity of the osteoclasts involved in the macrophage reaction. No toxicity on the different cell lines surrounding the material was observed, and this remained the case throughout the investigation. At 4 weeks also, we observed fragments of material brought into the bone tissue along tunnels made by osteoclasts. It was interesting to note that small pieces of material, detectable in polarized light microscopy, were found within the cytoplasm of osteoclasts (Fig. 2). The demonstration that these macrophages were indeed osteoclastic was based upon specific staining for acid phosphatase activity" and by their presence within lacunas of resorbing bone. At 8 weeks, a fibrous capsule surrounded the implant. The bone developed around the material has an Haversian structure and seems very basophilic. At 4 and 8 months, ossification of the fibrous capsule and bone apposition near the material and beside the osteoclastic activity were observed. Ossification of the capsule progressed by the formation of small bone islands. At 1 year, we witnessed the continuation of the fragmentation of the material with the presence of fragments into the apposed bone . No trace of the implanted material was ever detected in any organ that we examined, although only a part of the concerned organs have been investigated up to now.

Biomechanics Bending All the load-deflection curves in bending are of the

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F. Buron et al. BENDING - B1

LOAD (N)

120

SHEAR- 816

LOAD (N)

3.5 , - - , - --

-

- --

-

- - --

-,

3

100

2.5

80

2 60 1.5

40 20 0

0.5 2

0

8

6

4

10

12

o a

DEFLECTION (MM)

Fig. 3. Load-deflection curve in bending.

- maximal load obtained at the end of the test: 95·6 N (N = 20; SD = 5·8 N); -maximal deflection: 8'3mm (N = 20; SD = O'4mm); -maximal bendin~ stress: 2 55·4 N/mm (N = 20; SD = 5·8 N/mm ) ; -Young's modulus: 2 3730 N/mm 2 (N = 20; SD = 285N/mm ) . Shear

Two types of load-deformation curves are observed. In the first type (Fig. 4), a maximum is SHEAR - 81A

3.5.--.0--

-

-

-

-

-

-

-

-

-

0.4

0.6

0.6

1

1.2

1.4

1.6

DISPLACEMENT (MM)

Fig. 5. Shear load-displacement curve with rupture in one step.

same type (Fig. 3). After a loading of about lOON and a maximum deflection of some 10mm, we obtained a permanent deflection (±O.5 mm); we never achieved the rupture of the rod. Only the first part of the curves are linear. The Young 's modulus is given for this part of the curve. The bending stress is given at the end of the linear part (elastic limit). Further on, the laws based on linear elasticity and small deformations are no longer appropriate. We obtained the following values for some parameters of the bending tests:

LOAD (N)

0.2

---,

followed by a flat which reflects a double rupture of the rod in two steps. In the second type (Fig. 5), there is only a maximum, reflecting a simultaneous double rupture. The irregular aspect of the descending slope of the curve reflects the fact that all the fibers did not break at the same time. Finally, the slow descent is the result of the friction of the rod in the device. Our value for the mean shear stress is 141 N/mm 2 (N = 40; SD = 7N/mm 2) . Further tests will be performed after immersion of the rods in a saline solution , and the results compared to the tests of corresponding durations of implantation to detect a possible cellular or enzymatic action on the biomechanical behavior. Radiology

The aspect of the density curves seems to depend upon the duration of implantation. At the time of implantation the density distribution at the interface shows abrupt transition between bone and BOP, which smoothens after 1 year. Only a statistical analysis of the curves obtained for all the femurs compared to the histological slides will provide the appropriate information on the bone-implant interface.

3

2.5

CONCLUSION

2 1.5 -

0.5

a

a

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

DISPLACEMENT (MM)

Fig. 4. Shear load-displacement curve with rupture in two steps.

We have attempted to realize a triple experimental approach to a composite material. From our histological investigations, we can begin to understand, with a certain precision, the interactions between the bony tissue and the evaluated biomaterial. The goal of our biomechanical tests was to help us deduce the mechanical behavior of the material after implantation. Our radiological

Biocompatible osteoconductive polymer

analysis hopefully permits us to envisage the radiological criteria of osteoconduction.

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