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PubMed1998

Bone replacement grafts. The bone substitutes.

Bone substitutes will play a pivotal role in the future of periodontal regeneration. They are synthetically derived or processed from exoskeletons of other species (xenograft) and are an alternative to autogenous or allogeneic bone replacement grafts. Bone substitutes do not provide the cellular elements necessary for osteogenesis, and they cannot be considered osteoinductive, but instead are osteoconductive, providing a scaffold for new bone deposition. Currently, significant decreases in clinical probing depth and attachment levels have been reported with bone substitutes when compared to flap debridement surgery alone for periodontal osseous defects. Reported differences among bone substitutes, autogenous grafts, and allograft materials, occur with respect to histologic outcomes. Overall, probing depth reduction and attachment level gains are similar for all bone replacement grafts.

Alveolar Bone Loss↗
PubMed2001

Validation of bone conversion in osteoconductive and osteoinductive bone substitutes.

Bone reconstruction can be performed with an autogeneic graft from various donor regions. Osteoconductive and osteoinductive bone substitutes originate from substances of diverse chemical and morphological types and can have a synthetic or a biological derivation. Alongside autogeneic bone transplants and allogenic and xenogeneic bone implants, alloplastic bone replacements of synthetic or semi-synthetic origin are being used for defect reconstruction. In an animal model in rabbits five bone substitutes and one autogeneic graft were surgically incorporated into identical bone defects (10times 10 mm in size) in six anatomically defined regions of the skull. With scintigraphic and histological methods, the metabolic dynamics of the bone is examined as it reacts to the transplantation of autogeneic bone or to implanted bone replacement material.The different autogeneic, xenogeneic and alloplastic bone replacement materials can be differentiated according to the functional quality of the new tissue and the dynamics of the bone conversion thus induced. In the comparison of mineralized, osteoconductive bone subsitutes (TCP, HA, calcium carbonate ceramics) with demineralized, osteoinductive implants (DBM new, DBM old) and autogeneic bone grafts, the bone inducing matrices show the largest quantity of new bone formation, making possible a volume-constant reconstruction.

Journal Article↗
PubMed2003

Modification of gene expression induced in human osteogenic and osteosarcoma cells by culture on a biphasic calcium phosphate bone substitute.

Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells are very promising alternatives to autologous bone graft. Along this line, the development of in vitro models, dedicated to analyze the influence of these biomaterials on osteogenic cells, will help to improve the performance of these bone substitutes. In the present work we analyzed the effects of a macroporous biphasic calcium phosphate ceramic (BCP, Triosite) on three different human osteosarcoma cell lines and on human primary osteogenic cells and compared this culture substratum to traditional culture on plastic. We showed that all these osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a different spatial organization for osteosarcoma cells compared to normal osteogenic cells. We also demonstrated that osteoblastic marker genes such as Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed at similar levels by these cells cultured on either substratum, suggesting that adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we provided the first evidence of differences of cytokine expression profiles revealed on this Ca-P ceramic as compared to expression in classical culture. These modifications affected the expression of cytokines such as TGF-beta1, G-CSF, and IL-3 and were quantitatively different between osteosarcoma cells and normal osteogenic cells. Given the role of these cytokines in bone biology and in hematopoiesis, these results obtained in vitro suggest that the BCP ceramic studied here could stimulate osteogenesis in vivo by activating cellular processes during bone formation and healing. This study highlights the notion that the nature of the culture substratum must be taken into account when studying bone cell biology in vitro. Owing to the nature and spatial organization of the BCP, our hypothesis is that culture on BCP is closer to the physiological situation than culture on plastic.

Adolescent↗
PubMed1999

Bone and bone substitutes.

Bone replacement grafts will play a continuing role in periodontal and other regenerative therapy. Several choices are available to the clinician including autogenous, allogeneic, xenogeneic and a variety of alloplastic materials. Except for fresh autogenous bone, bone replacement graft(s) do not provide the cellular elements necessary for osteogenesis nor can they reliably be considered truly osteoinductive, but instead are mostly osteoconductive, providing a scaffold for bone deposition. Currently, significant decrease in clinical probing depth and gain of clinical attachment have been reported following use of bone replacement grafts when compared to flap debridement surgery alone for periodontal osseous defects. Reported differences among bone replacement grafts (autogenous, allogeneic, xenogeneic, and alloplastic) occur with respect to histological outcomes. Overall, probing depth reduction, attachment level gain and degree of defect fill are similar for all bone replacement grafts.

Alveolar Ridge Augmentation↗
PubMed2004

The issue of bioresorption of the Bio-Oss xenogeneic bone substitute in bone defects.

Bone grafts and bone substitute biomaterial implemented in guided tissue regeneration should undergo the process of biological decomposition in the recipient's system. The aim of this work is the presentation of current views concerning the issue of Bio-Oss bovine bone bioresorption and their juxtaposition with the results of the author's own research. The work presents histopathological and immunohistochemical tests of the xenogeneic Bio-Oss preparation from biopsies carried out 30 months after implantation. It was observed that the preparations contained correct bone neighbouring remnant particles of Bio-Oss, intratrabecular fibromatosis around the implant, abundant vascularisation, absence of osteoid and of active inflammatory process. A small number of T and B lymphocytes was detected. The results obtained in the above-described case testify to the descending character of the inflammatory infiltration 30 months after the implementation of Bio-Oss and efficient restoration of the bone. The prevalent view in literature is that Bio-Oss is resorbable biomaterial. However, there are also reports questioning this view as remnants of Bio-Oss have been detected even 44 months after implantation into the bone defect. In the author's own cases, Bio-Oss remnants could be observed 30 months after implanting. It seems that although the creation of new bone structure is indisputable, the process of biological decomposition of Bio-Oss should be described as slow bioresorption.

Biopsy↗
PubMed1997

Tri-calcium phosphate ceramics and allografts as bone substitutes for spinal fusion in idiopathic scoliosis as bone substitutes for spinal fusion in idiopathic scoliosis: comparative clinical results at four years.

The authors present the results of a comparative study of two series of posterolateral arthrodeses for scoliosis performed using COTREL DUBOUSSET instrumentation. Fifty-four consecutive patients underwent surgery for idiopathic scoliosis using the same technique. Thirty received a graft consisting of a mixture of corticocancellous autologous and allogenic bone frozen at -80 degrees, and 24 patients were grafted with a mixture of cortico-cancellous autologous bone and sticks of tricalcium phosphate (TCP, Biosorb, SBM, Lourdes, France). All patients were seen at three, six and twelve months, then once a year for at least four years with clinical and radiological evaluation at each visit. At the final follow up visit, no radiologic signs of pseudoarthrosis were found in either group with a minimum follow-up of 4 years. The appearance of bone callus was considered satisfactory at 6 months in all cases; moreover callus seemed to be more important in the TCP series, although this assessment was subjective. TCP resorption was total after 2 years, while allograft fragments were visible on x-rays after 2 years. Minor mechanical complications occurred but did not influence the results. Loss of correction was 8% of that initially obtained in the allograft group and 2% in the TCP group. Loss of correction did not progress after 6 months in the TCP group and after 2 years in the allograft group. Based upon this experience, the use of synthetic bone substitutes such as TCP would appear to be a valuable alternative to allografts in posterolateral spinal arthrodesis for idiopathic scoliosis, and it would eliminate the risk of viral contamination inherent to allograft implantation. To our knowledge, there have been no previous comparative studies concerning the use of tricalcium phosphate versus allograft in the literature.

Adolescent↗
PubMed2006

Finite element analysis of different bone substitutes in the bone defects around dental implants.

PURPOSE: To evaluate the distribution of stress and strain for the evaluation of implant and graft stability at each stage before stabilization of the graft is achieved after implantation was performed. MATERIALS AND METHODS: Dembone (Pacific Coast Tissue Bank, Los Angeles, CA), Bio-Oss (Geistlich Pharma, Wolhusen, Switzerland), particulate dentin, and plaster of Paris were used to fill bone defects. The distribution of stress was compared in the mandible and maxilla, between vertical load and load applied at 30 degrees angle, and according to time, with 3 different graft materials. RESULTS: Stress occurred more when it was applied at an angle, rather than applied vertically. Stress was relatively high immediately after implantation, and particulate dentin-plaster of Paris showed larger mechanical properties and lower stress distribution overall. The largest stress distribution was shown when stress was applied at an angle when demineralized freeze-dried bone was used. The pattern of stress distribution was different according to differences in the mechanical properties of implants. CONCLUSION: Caution is needed not to apply stress at an angle immediately after implantation. Differences of stress were reduced with time as the implant became stabilized.

Adult↗
PubMed1999

Hydroxyapatite as a bone substitute.

A bone substitute eliminates the need for autogenous and allogeneic bone grafting, along with the complications unique to each. Coralline hydroxyapatite is a synthetic bone void filler manufactured from marine coral, which has a natural trabecular structure similar to that of cancellous bone. While initial studies have been promising, the use of coralline hydroxyapatite may be limited in the foot and ankle owing to its inherent mechanical weakness and lack of biodegradation. In this retrospective study, 20 patients who received coralline hydroxyapatite implants were reviewed to determine associated complications and host reaction to the material. The results indicate that the material is biologically inert and safe to use as a small-defect filler in low-load applications. Long-term clinical trials are needed to determine the indications for this material in the foot and ankle.

Adult↗
PubMed1998

An experimental study on rhBMP-2 composite bone substitute for repairing craniomaxillary bone defects.

OBJECTIVE: To measure bone regenerative effects in animal calvarial or mandibular critical-size defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with four selected carriers. MATERIALS AND METHODS: The composite bone grafts were obtained by combining rhBMP-2 with chitin, coral, coral-based porous HA (CHA), and xenogeneic cancellous bone, respectively. These materials were implanted on the calvarial or mandibular defect of rabbits and on the calvarial defect of rats. Each carrier material was also studied as a control group. The animals were examined 2, 4, 8, and 12 weeks after implantation by radiography, histology (under light microscope and scanning electron microscope), immunohistochemistry, and biomechanics. RESULTS: The results showed that the composite graft was absorbed gradually after it was implanted into the defect, during which time new bone was formed within the combined material in the defect site; the amount of new bone increased as time elapsed. At 12 weeks the composite was replaced completely by bone except in the CHA group. In contrast, a large amount of fibrous tissue, and little new bone, formed on the area of the bone defect when the carrier material alone was implanted. CONCLUSIONS: All materials tested seem to be suitable carriers for rhBMP-2, which plays a very important role in new bone formation. These composite bone substitutes may be ideal materials for repairing various bone defects in the craniomaxillofacial region.

Animals↗
PubMed1997

In vitro cell behavior of osteoblasts on Pyrost bone substitute.

BACKGROUND: Pyrost bone substitute has been shown to be a promising orthopedic biomaterial. However, little is known about mechanisms that are responsible for the genesis and development of the bond between bone and the Pyrost bone substitute. The purpose of this study is to elucidate the in vitro cell behavior of osteoblasts on Pyrost bone substitute. METHODS: By using primary culture of rat osteoblasts, the changes in cell morphology during adhesion and flattening onto the surface of Pyrost bone substitute were studied in vitro. At 1 hour, at 3 hours, and at days 1, 3, and 7 after layering, the cell behavior was observed with scanning electron microscope. RESULTS: The processes of trypsinized osteoblast adhesion and spreading on Pyrost bone substitute consisted of 1) contact of rounded osteoblasts with the Pyrost substrate; 2) attachment of osteoblasts at point of contact; 3) centrifugal growth of filopodia; 4) flattening and spreading of the osteoblasts on the Pyrost substrate; 5) division and growth of osteoblasts; and 6) suspension of the osteoblasts across the pores by their processes. CONCLUSIONS: These results demonstrated that Pyrost can form a physico-chemical bond with osteoblasts. The Pyrost bone substitute not only supports osteoblasts attachment but also allows proliferation of the osteoblasts.

Animals↗
PubMed2001

A bone replaceable artificial bone substitute: osteoinduction by combining with bone inducing agent.

Bone inducing agent (BIA) isolated from Saos-2 human osteosarcoma cells was added to an artificial bone substitute composed of 980 degrees C-heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in wt/wt %), and a CAp-AtCol-BIA substitute was prepared as an osteoinductive bone substitute. Rat calvaria osteoblasts treated by the isolated BIA demonstrated significantly increased alkaline phosphatase (ALP) activity after 3 days (p < 0.05). In vitro cell attachment and proliferation and ALP activity were investigated for the bone substitute combined with BIA. Osteoblasts cultured onto the surface of the CAp-AtCol-BIA substitute demonstrated remarkable morphological changes such as radial spreading, flattening, and projecting filopodia after 5 days. In comparison with the substitute without BIA, osteoblasts grown in the BIA-combined CAp-AtCol substitute expressed significantly increased proliferation and ALP activity, respectively (p < 0.05). Both the substitutes combined with and without BIA were implanted into artificial defects created in rabbit radii. After 4 weeks, the CAp-AtCol-BIA substitute implanted lesion was completely replaced by regenerated host bone in radiological observation whereas the substitute without BIA was partially resorbed. No histologic abnormalities appeared in the substitute either with or without BIA.

Alkaline Phosphatase↗
PubMed1986

[Biological value of various bone substitutes in the treatment of bone defects. Animal experiment studies].

In clinical practice, biologic and synthetic substances have been used more and more as bone substitutes during the last few years. Different properties of the implant material are required according to the various fields of application. This implies a precise investigation of the biologic value by adequate experimentations on animals. It has been demonstrated in a bioassay with several synthetic implant materials, especially ceramics made of calcium phosphate, powders and granulated materials of tricalcium phosphate, and hydroxylapatite with different pore sizes and numbers, that there is only poor or even not any biologic activity in these substances which would produce an orthotopic stimulation of osseous formation. The application of these substances as bone substitutes can only be recommended in an adequate transplantation bed. However, all implant materials tested by different experimentations on animals showed an incomplete absorption in the histomorphological investigation even after twelve months. The various biologic bone substitutes (autologous and homologous spongiosa, demineralized homologous spongiosa, different forms of bone gelatin) show different degrees of biologic activity. Hitherto an inducing heterotopic effect could be demonstrated for bone gelatin in rats, dogs, and sheep. The inducing effect of bone gelatin combined with soluble calcium phosphate ceramics in rats was increased as compared with autologous spongiosa. Regarding our own results as well as various communications in literature, we consider it absolutely necessary to give more attention to the objectifying criteria when describing the biologic activity of "biologic and synthetic bone substitutes".

Animals↗
PubMed2003

[Bone substitution and remodeling of the jaw bones. A review].

Replacement of defects of the jawbones is one of the rapidly developing fields of maxillofacial surgery. The main criterion for the success of bone replacement is effective remodelling, i.e. the quantitative transformation of the inserted bone-substitute material into bone of the same quality and the same structure as the original. The aim of this report is to survey the literature background of our knowledge relating to remodelling. An account is given of the mechanism of transformation of the bone-substitute material into bone, and of clinical, radiological and histologic methods with which the transformation can be appropriately followed. Remodelling is a protracted process, and conclusions relating to it can be drawn only from examinations performed at isolated points of time, which are often difficult to objectify. We may speak of complete remodelling if the inserted material can no longer be recognized, and only bone with a structure agreeing with that of its environment is to be seen in the augmented area.

Bone Remodeling↗
PubMedDate not supplied

Bone healing following the use of hydroxyapatite or ionomeric bone substitutes alone or combined with a guided bone regeneration technique: an animal study.

The healing of standardized bone defects grafted with either particulate ionomeric or hydroxyapatite bone substitutes was compared in the mandibular ramus of 30 Sprague-Dawley rats. The possible additional response achieved when combining these materials with a guided bone regeneration (GBR) technique was also evaluated. Three groups of 10 animals received either no implant material or ionomeric or hydroxyapatite bone substitute in defects in the right ramus. The left mandibular defects received the same treatment, except that the operation site was covered by a membrane (GBR technique). Half of the animals were sacrificed at 4 and 10 weeks following surgery, and the inflammatory response at the implant site and the amount of new bone formed in the defects were determined histomorphometrically. Defects implanted with ionomeric bone substitute exhibited more bone formation (4 weeks = 3.19 +/- 0.35 mm2, 10 weeks = 5.35 +/- 0.26 mm2) than both defects that received no treatment (4 weeks = 0.88 +/- 0.35 mm2, 10 weeks = 2.1 +/- 0.49 mm2), membrane alone (4 weeks = 1.21 +/- 0.05 mm2) or hydroxyapatite bone substitute (4 weeks = 1.41 +/- 0.46 mm2, 10 weeks = 3.34 +/- 0.41 mm2) at 4 weeks (P < or = .01) and at 10 weeks (P < or = .05). The use of a GBR technique did not increase the amount of bone formed, compared to the use of bone substitutes alone. Hydroxyapatite and ionomeric bone substitutes used alone were more effective in inducing repair of the defects than was GBR membrane alone. The use of hydroxyapatite was associated with a greater inflammatory reaction (P < or = .01) than was ionomer in this model.

Analysis of Variance↗
PubMed2005

Fibrin gel-immobilized primary osteoblasts in calcium phosphate bone cement: in vivo evaluation with regard to application as injectable biological bone substitute.

Osteogenic injectable bone substitutes may be useful for many applications. We developed a novel injectable bone substitute based on osteoblast-fibrin glue suspension and calcium phosphate bone cement (BC). Human osteoblasts were isolated from trabecular bone samples and cultured under standard conditions. Osteoblasts were suspended in fibrinogen solution (FS). BC was cured with thrombin solution. 8 x 4 mm injectable bone discs were prepared using silicon molds and a custom-made applicator device. Discs containing BC, BC/FS, or BC/FS/osteoblasts were implanted subcutaneously into athymic nude mice. After 3, 9 and 24 weeks, specimens were explanted and subjected to morphologic and biomechanical evaluation. In vitro fibrin gel-embedded osteoblasts displayed a differentiated phenotype as evidenced by alkaline phosphatase, collagen type 1 and von Kossa stains. A proportion of osteoblasts appeared morphologically intact over a 3-day in vitro period following application into the BC. BC/FS and BC/FS/osteoblast discs were sparsely infiltrated with vascularized connective tissue. There was no bone formation in implants from all groups. However, positive von Kossa staining only in BC/FS/osteoblast groups suggests engraftment of at least some of the transplanted cells. Biomechanical evaluation demonstrated initial stability of the composites. Young's modulus and maximal load did not differ significantly in the BC/FS and BC/FS/osteoblast groups. The practicability of osteoblast-containing injectable bone could be demonstrated. The dense microstructure and the suboptimal initial vascularization of the composites may explain the lack of bone formation. Modifications with regard to enhanced osteoblast survival are mandatory for a possible application as injectable osteogenic bone replacement system.

Adult↗
PubMed2002

Histological assessment of augmented jaw bone utilizing a new collagen barrier membrane compared to a standard barrier membrane to protect a granular bone substitute material.

Successful bone augmentation requires predictable space maintenance and adequate exclusion of those cells that lack osteogenetic potential from the defect area. Natural bone mineral is considered to be osteoconductive and is used as space maker in combination with membrane barrier techniques. The aim of this study was to compare qualitative histological results achieved by using deproteinized bovine bone mineral (DBBM) as a space maintainer and a new collagen barrier (Ossix, test group) vs. the same bone substitute and the standard e-PTFE membrane (Gore-Tex), control group). Twenty-eight patients were randomly assigned to the test or the control group. Seven months after augmentation procedures, biopsies were obtained at reentry and were analysed histomorphometrically. In all, 14 specimens of group I (test group, Ossix) and 13 specimens of group II (controls, PTFE-membranes) showed close qualitative similarity of their histologies. Histomorphometrically, total mineralized bone area was 42% +/- 18% in group I vs. 39% +/- 15% in group II. The unmineralized tissue area was 44% +/- 15% vs. 46% +/- 12% and the area of DBBM remnants 14% +/- 9% and 15% +/- 12%, respectively. The differences were statistically nonsignificant (Mann-Whitney test). The occurrence of barrier exposure did not interfere with the histological outcome either in the test or in the control group. The new collagen barrier combined with the DBBM provided qualitative bone regeneration comparable to the standard e-PTFE material combined with the same mineral.

Absorbable Implants↗
PubMed1991

[Bone substitution using allogenic bone preserved in methiolate].

Based on their own material authors analyse the results after implantation of merthiolate-banked allogenic bone grafts; 327 cases are reviewed grouped according to the size of the graft. Based on the radiographic picture the healing period was measured in each case. It is stated that no clinical evidence of any immunologic reaction was found in this material. The described method can be an alternative way of bone grafting in those cases where autotransplantation cannot provide the desired amount of bone or its risks are present.

Bone Neoplasms↗
PubMed1996

Enhanced healing of segmental tibial defects in sheep by a composite bone substitute composed of tricalcium phosphate cylinder, bone morphogenetic protein, and type IV collagen.

Diaphyseal segmental defects in the tibia of 18 sheep were used to evaluate the healing potential of a composite bone substitute device (CBS) composed of a tricalcium phosphate cylinder (TCP), naturally occurring sheep bone morphogenetic protein (sBMP), and type IV collagen. A total of 100 mg of sBMP and 20 mg of type IV collagen in the high-dose group (CBSH), and 13 mg of sBMP and 2.5 mg of type IV collagen in the low-dose group (CBSL) were adsorbed to TCP cylinders, respectively. TCP cylinders impregnated with type IV collagen alone (TCPC) were used as control. A significantly larger area and more highly integrated intensity of newly formed external callus between CBSH and CBSL or TCPC group were quantified by computerized image analyzer at both 3 and 6 weeks. A torsion test showed that the maximal torque capacity, maximal angular deformation, and bone stiffness of healed osteotomized tibia with implants recovered 117-125% in CBSH, 72-109% in CBSL, and 63-80% in TCPC, compared with the corresponding contralateral tibia at 16 weeks. A healing superiority of the segmental bone defects replaced by the implants was demonstrated in the CBSH group. Thus, the composite bone substitute device defined in this study was shown to possess osteoinductivity, osteoconductivity, and mechanical strength.

Animals↗