[Bone substitution materials].
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The control of porosity morphology and physico-chemical characteristics of calcium phosphate bone substitutes is a key-point to guaranty healing success. In this work, micro- and macroporosity of materials processed with 70% Hydroxyapatite (HAP) and 30% beta-tricalcium phosphate (beta-TCP) were controlled by sintering temperature and porogen addition, respectively. Porosity was quantified by scanning electron microscopy (pore size) and mercury intrusion porosimetry (interconnection between pores). The content of macrointerconnections and their size were dependent on porogen content, shape, and size. Mechanical properties (compressive strength) were strongly dependent on macroporosity size and content, on the basis of exponential laws, whereas microporosity ratio was less influent. Relying on those results, three types of materials with contrasting porous morphologies were processed and assessed in vitro, in primary culture of human osteoblasts and fibroblasts. With both types of cells, an exponential cellular growth was effective. Cells colonized the surface of the materials, bridging macroporosity, before colonizing the depth of the materials. Cell migration across and into macroporosity occurred via the emission by the cells of long cytoplasmic extensions that hanged on microporosity. Both macroporosity and macrointerconnectivity size influenced the penetration of cells. An interconnection size of 15 microm appeared to be effective to support this invasion without bringing down mechanical strength.
Biomaterial research and tissue engineering have guided new developments in bone replacement. In this study, the osteoconductive and osteoinductive properties of 45S5 Bioglass (Novabone-C/M, Porex Surg., Newnan, GA), granules as a bone replacement material for large calvarial defects were evaluated. Rabbit periosteal cells were expanded in culture and used in vivo. Alkaline-phosphatase assay, collagen type I, and calcium expression were applied to confirm osteoblast phenotype. In the in vivo phase, a 15-mm diameter critical size calvarial defect was created in rabbits (n = 14). The defect was reconstructed according to four treatment groups: autogenous bone (n = 2), Bioglass alone (n = 2), Bioglass + bone (n = 5), Bioglass + periosteal cells (n = 5). The animals were killed 12 weeks after surgery, and the samples were analyzed. Periosteal cells grew successfully in vitro. Because of their fast proliferation and potential to differentiate into osteoblasts, they were an excellent source of cells for bone tissue engineering. The best ossification was seen when autogenous bone was used (79.4% ossified), whereas only 8.2% of the defect in the Bioglass group showed ossification. Addition of bone or cells to the Bioglass increased the area of ossification to 42.7% and 30.2%, respectively. Defects replaced with Bioglass showed varying degrees of inflammatory reaction because of the intense cell-mediated biodegradation process. Based on these findings, the use of Bioglass granules to repair large craniofacial defects cannot be advised.
The aim of the present retrospective study was to evaluate the performance of bone graft substitutes currently in use. After exclusion of those with inadequate data for comparison, 70 out of the 101 operated fractures remained available for statistical analysis. Grafts were used in 38 cases: 23 were bone substitutes and 15 autogenous grafts. Distal radial inclination and lateral angles showed no significant difference. Analysis of ulnar variance showed the relative inability of intramedullary pinning to maintain radial length in the absence of graft. In contrast external fixators preserved radial length both with and without bone grafts, and with all types of graft material. TCH (hydroxyapatite and calcium phosphate) or autogenous bone grafts allowed intramedullary pinning to maintain radial length; whereas collagen matrix material was ineffective. We conclude that TCH and autogenous bone grafts have equivalent effectiveness despite potential bias in this study.
The aim of this retrospective study was to report the preliminary results of femoral peri-prosthetic bone defect reconstruction with a synthetic bone substitute. Twenty-one revisions of the femoral component in 20 patients were evaluated. The mean age at operation was 65.7 years (range, 30 to 79 years). Preoperative femoral deficiencies were rated grade II in 7 cases and grade III in 14 cases according to the SOFCOT classification. None was rated grade IV. Femoral revision was indicated for loosening in 18 hips (including 8 septic cases), femoral osteolysis (1 hip), persistent pain (1 hip) and recurrent dislocation (1 hip). Once the loose prosthesis had been removed, calcium phosphate ceramic (CPC) granules (14 cases) or ceramic granules + cancellous allograft (5 cases) or autograft (2) were firmly impacted in the femoral canal. The stem was standard and always cemented using modern cementing technique. At a mean follow-up of 36 months (range, 14 to 76 months), 90% of the hips were rated good or very good according to the Merle d'Aubigné score. Two diaphyseal femoral fractures occurred and later united. Two hips required re-revision (aseptic loosening; septic recurrence). The absence of radiological osteolysis in 17 cases suggested direct bonding between ceramic granules and bone. Stem subsidence occurred in two cases and was limited (5 and 8 mm). Femoral bone reconstruction using impacted CPC or CPC in conjunction with bone graft in revision hip replacement commonly provided restoration of the bone stock in the short to mid-term. Further long-term studies will be necessary to support this conclusion.
We investigate the relevance of site-bond percolation theory to model the resorption and ossification of natural coral implanted in bones. The first step of the process is the vascularization of the implant seen here as a percolation threshold. The resorption and ossification can thus take place by activation of unoccupied sites. We compare our results with previously obtained experimental data on implants in porcine cortical bones. Very encouraging results are obtained.
A new porous ceramic material was tested for possible use as a bone substitute in regions exposed mainly to compressive forces. The porous ceramics were implanted into the medial condyle of the tibia of four sheep and left in position for 3 months. The operated tibia was then removed and sections were made of the implants. The sections were studied by transmitted light microscopy, microradiography and scanning electron microscopy. There was no apparent loss of function of the operated leg and the implants were found to be bound to the adjacent bone by ingrowth of bony tissue, in some regions to a depth of 2-3 mm. It is concluded that the properties of the porous ceramic implants justify a clinical trial, provided that the results of long-term animal experiments are equally satisfactory.
With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.
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In this study, Frost's bulk-staining in combination with confocal laser scanning microscopy (CLSM) was used to image and characterize ground sections of undecalcified rat bone tissue with in situ bioceramic implants. This was addressed by bulk staining specimens in alcohol-soluble basic fuchsin dye. The ground sections were imaged using CLSM in the confocal fluorescence mode. Confocal images revealed that the newly formed bone could be clearly distinguished from bone marrow and cortical bone, as well as from the implant material.
Tissue response to a readily consolidating material prepared by mixing alpha-tricalcium phosphate (alpha-TCP) powder with a glycolic acid dextran solution and to this consolidating material combined with particulate hydroxylapatite (HA) was studied after implantation in the subperiosteal space of the mandible in rabbits. Active new bone formation comparable to that seen on HA implants was observed around the two compounds. The newly formed bone was in direct contact with the HA as well as the readily consolidated material and little adverse effect resulting from the glycolic acid and dextran was observed. Because the readily consolidating material was firm and could be contoured into any shape during the process of consolidation, it may be quite useful as a bone substitute and as an adherent for HA particles for reconstructive bone surgery, overcoming the disadvantages inherent to the particulate form of HA.
For the treatment of bony defects in the skeleton, today there are five different options. Filling a defect by the application of autogenous bone is one of them. Autogenous cancellous bone is still considered to be the gold standard, but numerous shortcomings of this material, described in detail in this paper, are not taken into account. Besides, we are still unable to influence bone healing by the transplantation of autogenous bone with reference to quality, quantity of newly forming bone and the time period, in which bone healing occurs. Investigation into the different kinds of biomaterial developed to replace autogenous bone as a transplant, and their implantation into experimental animals did not result in the production of a synthetic material that was as active as autogenous or even allogeneic cancellous bone. This was therefore not a solution to the problem. The reasons for this are multiple and are discussed in this paper. We developed a classification for bone replacement materials that differentiates between biological, synthetic, and composed materials, i.e., composite biomaterials made for bone replacement. In reference to the literature, as well as our own results, based on the implantation of more than 1200 rats, dogs, and sheep with distinct materials, the plus/minus effects of the different classes, groups and subgroups of bone replacement materials are summarized and discussed. The most recent knowledge about the mechanisms of bone formation and how it is influenced by different growth factors, as well as bioactive ceramics, indicates that in the future an applicable bone replacement material will be a composite of a carrier material combined with chemotactic, inductive, morphogenetic and proliferative, chemically pure, recombinant factors, with a mainly local action. Unfortunately, the road to get there is long.
A recent 3-month implantation study indicated that a new porous ceramic material might be suitable as a bone substitute in regions exposed mainly to compressive forces. The porous ceramics were implanted into the medial condyle of the tibia of sheep. In the present study the implants were left for 10 months in three animals, and 12 months in two. In the two animals with 12 months' observation, the plate which had been used to stabilize the implant was removed at 10 months. The implants and the adjacent bone tissue were studied macroscopically, radiographically and by microradiography and transmitted light microscopy. All the implants were bound to the adjacent bone by ingrowth of bony tissue. The depth of the bony invasion was slightly greater than that observed at 3 months, being maximally 3-4 mm. Some signs of ossification were still seen within the pores. The bony bridges between the implants and the surrounding bone were particularly well developed in regions of maximal stress. This was interpreted as a sign of active adaption of the bone formation to the actual stress to which the shearing surfaces were exposed. It is concluded that the properties of the porous ceramic implants justify a clinical trial in man.
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This study evaluated hydroxyapatite-glass (HA-G) composite as a filler material when implanted into a proximal metaphyseal tibial cavity consisting of medullary tissue and cancellous bone in rabbits. The repair process was compared with that of autogenous bone grafts and untreated controls. Scanning electron microscopy, energy dispersive x-ray studies, radiography, histology with tetracycline fluorescence and morphometric bone measurements were used for evaluation. Equal amounts of mineralised bone were produced in both HA-G granule and autograft groups at 3 weeks; thereafter, autografts mostly resorbed, whereas there was appositional lamellar bone formation on the early woven bone in the HA-group. A relatively small proportion of the cavities was repaired by new bone. The HA-G granules were biocompatible without foreign body reaction and showed good osteoconductive potential. Mesenchymal cells were able to differentiate into osteoblasts on bioactive surfaces of the composite. Although HA-G was able to form Ca-P-rich and Si-rich layers, most of the granules underwent degradation through its glass matrix, resulting in fewer bony contacts than granules with no surface degradation.
In order to avoid the potential risks of disease transmission in allograft surgery, numerous substitute materials have been described. As the biological response to implant materials is different, we undertook the following study to assess type and amount of bone ingrowth in CaP-ceramics. 105 cylindrical bone defects with a diameter of 5.4 mm were created surgically in the femoral condyles of 53 skeletal mature NZW rabbits. The defects were filled with crushed coralline hydroxyapatite (HA) implants (n = 21), synthetically produced hydroxyapatite (n = 21) and surface-modified alpha-Tricalciumphosphate (TCP) grains (n = 21). 21 defects were left empty and other drill holes were filled with rabbit cancellous bone cylinders (n = 21) after 3 months of cryopreservation at -78 degrees C without sterilization. Following observation periods of 2, 4, 6, 8, 12, 26 and 52 weeks the femoral condyles were harvested for histological evaluation and quantitative analysis of bone ingrowth. Woven bone formation at implant periphery can be observed in all substances as early as 2 weeks postoperatively. At 4-week-intervals cryopreserved allografts show new bone apposition on surfaces of necrotic trabeculae and graft-host junctions by a predominantly osteoblastic reaction at the periphery of all cylinders, while in HA- and TCP-grains early bone formation in the center of drill holes is detectable as well. There is a direct contact between HA-/TCP-particles and newly formed bone without fibrous tissue formation at the implant surfaces. Central new bone formation in rabbit allografts can be observed after 6 to 8 weeks together with a secondary osteoclastic resorption of necrotic transplant trabeculae. The result of this remodeling process is a complete degradation of transplant cylinders with reorganization of vital trabeculae oriented in a mature pattern after 12 to 26 weeks. In contrast the HA- and TCP-implants did not show any signs of resorption.
For the treatment of bony defects of the human skeleton there are different options. If a defect has to be filled up, autogenous cancellous bone is recommended as the 'golden standard', i.e. the material of choice for such procedures, ignorant to the fact that autogenous bone transplants are not without consequences to the patient and that their harvesting and transplantation might be connected to certain complications. As an alternative, there have been attempts to implant bone replacement materials as a substitute for the autogenous tissue. Despite a longstanding history of research in this field up to now a clinically applicable alternative could not have been found. Aim of the article is to classify the different compounds recommended for bone replacement. After a description of the development of the materials in the different classes, the state of the art and today's knowledge of how the different materials elicite their effects, an outlook into possible future developments is given for each class. Finally recommendations for today's clinical use of the bone substitutes are presented.
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