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At least 451 records · Page 25Linked to original sources
PubMed2005

Physiologically clotted fibrin-calcined bone composite--a possible bone graft substitute.

Fibrin plays a major role in blood clotting and is important in wound healing. In the present study, physiologically clotted fibrin (PF) and calcined bone (CB) both of bovine origin were used in the preparation of a bone graft material with chitosan (C) as a binder. This bone graft (PF-CB) was characterized by stress-strain analysis, X-ray diffraction (XRD) studies, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and FTIR spectroscopy. Thermal studies revealed that the incorporation of CB into PF did not alter the thermal stability of fibrin, although it affects the total loss percentage. The composition containing 24:1:15 (PF:C:CB) on dry weight basis exhibited maximum compressive strength, and the same composite was used for characterization studies. The XRD studies have shown the amorphous nature of the implant. SEM pictures revealed the heterogeneity and porous nature of the implant. PF in combination with CB is expected to exhibit osteoinductivity because fibrin, the osteoinductive protein, acts as an angiogenic factor, whereas CB provides calcium and phosphate ions that are needed for new bone formation.

Animals↗
PubMed2000

Evaluation of recombinant human bone morphogenetic protein-2 as a bone-graft substitute in a canine segmental defect model.

A study was performed in dogs to evaluate the dose-response characteristics and effectiveness of recombinant human bone morphogenetic protein-2 with a collagen sponge carrier in a segmental defect model. Twenty-seven dogs underwent bilateral radial osteotomies with creation of a 2.5-cm diaphyseal defect. All received autogenous cancellous bone graft in one defect and a collagen implant in the other. These implants contained recombinant human bone morphogenetic protein-2 at the following doses: group 1 at 0 microg (three dogs, 0 microg/ml total implant volume), group 2 at 150 microg (three dogs, 50 microg/ml), group 3 at 600 ,g (three dogs, 200 microg/ml), group 4 at 2,400 microg (three dogs, 800 microg/ml), group 5 at 0 microg (five dogs, 0 microg/ml), group 6 at 150 microg (five dogs, 200 microg/ml), and group 7 at 600 microg (five dogs, 50 microg/ml). The defects were stabilized with external fixators. The dogs in groups 1-4 were killed at 12 weeks postoperatively, and those in groups 5-7 were killed at 24 weeks postoperatively except for one dog in group 7, which was killed at 48 weeks. Evaluation included monthly radiographs, biomechanical testing, and nondemineralized histology. All 27 radii with autogenous cancellous bone graft and all 19 implants treated with recombinant human bone morphogenetic protein-2 achieved radiographic and histologic union and gross stability. The eight radii treated with collagen carrier alone went on to radiographic and histologic nonunion and were grossly unstable at death. A dose-dependent occurrence of cyst-like bone voids was noted radiographically and histologically. Biomechanical performance tended to be better at the lowest dose studied at 12 weeks, and all three doses performed better than the placebo (p < 0.05) at 12 and 24 weeks. By 24 weeks, radiolucent areas corresponding to histologic bone voids persisted radiographically, although there was evidence of early bone remodeling. This remodeling progressed to 48 weeks in the single animal followed to this time point, although bone voids remained. These radiologic findings were confirmed histologically. Recombinant human bone morphogenetic protein-2 in a collagen sponge carrier has significant osteoinductive activity in this canine segmental defect model. A dose-response relationship is evident, with heterotopic bone and cyst-like void formation at higher doses and a minimum effective dose of 0-150 microg. At 12 and 24 weeks postoperatively, biomechanical parameters achieved by defects treated with recombinant human bone morphogenetic protein-2 were comparable with those of autograft controls and were significantly stronger than those of the placebo (p < 0.05).

Animals↗
PubMed1986

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation.

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.

Adolescent↗
PubMed2001

Synthetic hybrid grafts for craniofacial reconstruction: sustained gene delivery using a calcium phosphate bone mineral substitute.

These experiments were performed to evaluate the efficacy of a biocompatible bone cement, Norian CRS, engineered as a hybrid graft for simultaneous bone matrix reconstruction and sustained, site-directed gene transfer using an adenoviral vector. Norian CRS was cured ex vivo by mixing a calcium source powder with a phosphate source solution to form a paste. To 1.0 ml of the cement was added 50 microl of a solution containing 1 x 10(8) plaque-forming units of a replication-deficient adenoviral vector containing a bacterial beta-galactosidase reporter gene (AdLacZ). In vitro, fragments of the hybrid Norian-AdLacZ construct were placed into 12-microm-pore culture plate inserts and cocultured with human fibroblasts. The same insert was transferred to a new well of fibroblasts every 48 hours for 30 days, and, after allowing 72 hours for gene expression, fibroblasts were examined for transgene expression by 5 bromo-4-chloro-3-indoyl-beta-D-galactosidase (X-gal) staining. In vivo, the Norian-AdLacZ hybrid was implanted into 10-mm frontal bone defects in 3-week-old piglets. The implant sites were harvested after 5 days and were examined for transgene expression by X-gal staining. X-gal staining of fibroblasts incubated with the hybrid Norian-AdLacZ construct was observed throughout the 30-day period. Transgene expression was also observed about the periphery of the calvarial defects treated with hybrid Norian-AdLacZ constructs. Thus, adenoviral vectors may be incorporated successfully into a synthetic calcium phosphate bone mineral substitute to provide effective, sustained local gene delivery.

Adenoviridae↗
PubMed1997

Bovine-derived bone protein as a bone graft substitute in a canine segmental defect model.

OBJECTIVES: To evaluate the efficacy of a bone graft substitute in healing of a segmental defect of a weight-bearing long bone. DESIGN: An established canine model was used to perform a blinded, prospective, randomized study of the performance of bone graft substitute implants. This performance was compared with that of an accepted treatment modality (autograft) in a paired fashion. SETTING: An accredited animal research facility. SUBJECTS AND INTERVENTION: Twenty-eight dogs underwent bilateral radial osteotomies with creation of a 2.5-centimeter defect. On one side, the defect in every dog was filled with autogenous cancellous bone graft (ABG). Contralateral defects received, in a blinded, randomized fashion, cylindrical implants of demineralized bone matrix (DBM) allograft or DBM plus a constant dose (3.0 milligrams) of bovine-derived bone protein (DBM + BP). The defects were stabilized by external fixation. Subjects underwent monthly radiographs and were killed at six, twelve, or twenty-four weeks. Regenerate bone was studied by biomechanical testing and histology. Six animals were studied to determine the dose-response characteristics of the protein preparation. Three received implants containing 0.3 milligram of BP (group 1) and three received 1.0 milligram of BP (group 2). These animals were killed at twelve weeks of follow-up. RESULTS: All twenty-eight ABG radii (100 percent) progressed to radiographic union, as did thirteen of thirteen (100 percent) DBM + BP radii compared with only four of fifteen (27 percent) of DBM radii. The difference between union rates was statistically significant (p < 0.05). Mean values for most biomechanical parameters of DBM + BP radii exceeded those of their contralateral ABG controls at twelve and twenty-four weeks, whereas those for DBM implants did not. Histology revealed microscopic evidence of normal bone healing in all ABG and DBM + BP radii, whereas most DBM radii demonstrated nonunions. In the dose-response arm of the study, six of six ABG radii (100 percent) achieved union; zero of three (0 percent) of group 1 and two of three (67 percent) of group 2 radii achieved grossly stable unions. Biomechanical testing was consistent with radiographic results, indicating that the 3.0-milligram dose was the most effective of those studied. CONCLUSIONS: The DBM + BP composite implants were more effective at healing critical-sized segmental defects than DBM alone in this canine model when a 3.0-milligram per implant dose of BP was used. Biomechanical and histologic properties of the regenerated bone formed by DBM + BP implants was comparable to that of cancellous autograft.

Animals↗
PubMed2005

Effect of zoledronic acid on incorporation of a bioceramic bone graft substitute.

Many osteoporotic fracture patients are candidates for concurrent treatment with bisphosphonates and bioceramic bone graft substitutes. Osteopromotive silica-based bioactive glasses are known to induce accelerated local bone turnover and adjunct antiresorptive agents, such as zoledronic acid, may affect the process. The current study examined the effect of adjunct zoledronic acid therapy on bioactive glass incorporation. In Harlan Sprague-Dawley rats (n = 80), a standardized region of the proximal tibia was subjected to ablation of local bone marrow and filled with bioactive glass (BG) microspheres. Experimental animals received zoledronic acid (1.5 mug/kg, s.c., once a week, started 1 week before surgery) or doxycycline (a metalloproteinase inhibitor) (33 mg/kg, daily gavage) as a control agent. BG incorporation and geometric bone properties were followed by sequential pQCT imaging. The final outcome at 8 weeks was analyzed by digital radiography, histomorphometry, BEI-SEM, EDXA and muCT. The mRNA levels of markers for bone resorption (cathepsin K, TRACP, MMP-9, MMP-13) and synthesis (type I, II, III collagens, osteocalcin, osteonectin, osteopontin) were measured for determination of local bone turnover. Bones filled with BG microspheres produced 2.5-fold more intramedullary new bone than controls with bone marrow ablation only, but the BG filling delayed the recovery of pQCT strength strain index (SSI) of the bones. Adjunct therapy with zoledronic acid enhanced new bone formation on BG microspheres and particularly improved the SSI values of the BG-filled bones (P < 0.05). The zoledronic acid therapy alone (without BG filling) produced the highest amount of intramedullary new bone (6-fold more than in unfilled controls, P < 0.001) but did not show a similar benefit in SSI. The analyses of mRNA expression confirmed high local bone turnover in all bones with BG filling. At the 9th week of zoledronic acid treatment, bones with and without BG filling showed increased mRNA levels of bone resorption markers and decreased mRNA levels of markers for synthesis, indicating that a corrective resorption process was already in progress in response to massive accumulation of medullary new bone at earlier stages of the therapy. Adjunct antiresorptive therapy seems to be beneficial for incorporation of bioactive glass microspheres and does not block local natural remodeling processes. In the current model, the therapy even resulted in favorable remodeling of the tubular bone structure.

Absorptiometry, Photon↗
PubMed2003

Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel-titanium bone graft substitute.

Porous nickel-titanium (NiTi) alloy is a promising new material for a bone graft substitute with good strength properties and an elastic modulus closer to that of bone than any other metallic material. The purpose of this study was to evaluate the effect of porosity on the osteointegration of NiTi implants in rat bone. The porosities (average void volume) and the mean pore size (MPS) were 66.1% and 259+/-30 microm (group 1, n=14), 59.2% and 272+/-17 microm (group 2, n=4) and 46.6% and 505+/-136 microm (group 3, n=15), respectively. The implants were implanted in the distal femoral metaphysis of the rats for 30 weeks. The proportional bone-implant contact was best in group 1 (51%) without a significant difference compared to group 3 (39%). Group 2 had lower contact values (29%) than group 1 (p=0.038). Fibrotic tissue within the porous implant was found more often in group 1 than in group 3 (p=0.021), in which 12 samples out of 15 showed no signs of fibrosis. In conclusion, porosity of 66.1% (MPS 259+/-30 microm) showed best bone contact (51%) of the porosities tested here. However, the porosity of 46.6% (MPS 505+/-136 microm) with bone contact of 39% was not significantly inferior in this respect and showed lower incidence of fibrosis within the porous implant.

Animals↗
PubMed2001

Bone graft substitutes for the promotion of spinal arthrodesis.

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the "gold standard" for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor-beta, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans. The delivery of pluripotent mesenchymal stem cells (MSCs) to regions requiring bone formation is also compelling, and it has been shown to be successful in inducing osteogenesis in numerous preclinical studies in rats and dogs. Finally, the identification of biological and non-biological scaffolding materials is a crucial component of future bone graft substitutes, not only as a delivery vehicle for bone growth factors and MSCs but also as an osteoconductive matrix to stimulate bone deposition directly. In this paper, the currently available bone graft substitutes will be reviewed and the authors will discuss the novel therapeutic approaches that are currently being developed for use in the clinical setting.

Animals↗
PubMed1994

In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusions.

STUDY DESIGN: Posterior spinal fusion segments were evaluated in adult mongrel dogs at 6, 12, and 26 weeks post-implantation. Four sites on each animal received implants consisting of recombinant human osteogenic protein-1 on a bone collagen carrier, bone collagen carrier alone, autogenous iliac crest bone, or no implant material. OBJECTIVE: To determine the efficacy of recombinant human osteogenic protein-1 as a bone graft substitute in achieving posterior spinal fusion and compare the results to those obtained using autogenous bone graft. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion generally includes onlay grafting of autogenous or allogeneic bone after decortication of bony surfaces of the vertebral elements. The search for an acceptable bone graft substitute material has in recent years centered upon proteins capable of inducing bone in vivo. Recombinant human osteogenic protein-1 has demonstrated efficacy in healing large segmental osteoperiosteal defects in rabbits, dogs, and monkeys and appears ideally suited as a bone graft substitute for spinal fusions. METHODS: The quality of fusion and new bone formation was evaluated using plain films, computed tomography, and magnetic resonance imaging. RESULTS: Radiographic and histologic studies demonstrated that recombinant human osteogenic protein-1-treated fusion segments attained a stable fusion by 6 weeks post-implantation and were completely fused by 12 weeks. The autograft sites demonstrated fusion at 26 weeks post-implantation. CONCLUSIONS: The results indicated that recombinant human osteogenic protein-1 is an effective bone graft substitute for achieving stable posterior spinal fusions in a significantly more rapid fashion than can be achieved with autogenous bone graft.

Animals↗
PubMed2005

Bone graft substitute using hydroxyapatite scaffold seeded with tissue engineered autologous osteoprogenitor cells in spinal fusion: early result in a sheep model.

Spinal fusion using autologous bone graft is performed in an increasing rate for many spinal disorders. However, graft harvesting procedure is associated with prolonged operation time and potential donor site morbidity. We produced an engineered 'bone graft' substitute by using porous hydroxyapatite (HA) scaffold seeded with autologous bone marrow osteoprogenitor cells (OPCs) and fibrin. This obviates bone graft harvesting, thus eliminates donor site morbidity and shortens the operation time. The aim of this study is to evaluate Hydroxyapatite (HA) ceramics as scaffold for autologous tissue engineered bone construct for spinal fusion in a sheep model. The sheep's marrow was aspirated from iliac crest. The bone marrow mesenchymal stem cells (BMMSCs) were cultured for several passages in the presence of growth and differentiation factors to increase the number of OPCs. After the cultures reached confluence, they were trypsinized and seeded on Hydroxyapatite scaffold (HA). Approximately 5 million cells were generated after 3 weeks of culture. Microscopically, very tight Colony Forming Units (CFU-Fs) were seen on monolayer culture. The Von Kossa and Alizarin Red staining of monolayer culture showed positive mineralization areas; indicating the presence of OPCs. Sheep underwent a posterolateral spinal fusion in which scaffolds with or without OPCs seeded were implanted on both sides of the lumbar spine (L1-L2). Intended fusion segments were immobilized using wires. At the end of third month, the fusion constructs were harvested for histological examination. Fibrous tissue infiltration found in the inter-connecting pores of plain HA ceramics indicates inefficient new bone regeneration. New bone was found surrounding the HA ceramics seeded with autologous cells. The new bone is probably formed by the sheep BMMSCs that were initially encapsulating HA while it remained intact. The new bone is naturally fused with the vertebrae. In conclusion, the incorporation of autologous bone marrow cells improved the effectiveness of HA ceramics as 'bone graft' substitute for spinal fusion.

Animals↗
PubMed2003

Mechanical evaluation of a porous bone graft substitute based on poly(propylene glycol-co-fumaric acid).

A porous, resorbable polymer composite based on poly(propylene glycol-co-fumaric acid) (PPF) was mechanically evaluated in vitro for use as a bone graft substitute and fracture fixative. The test material created a dynamic system capable of initially providing mechanical integrity to bony voids and a degradative mechanism for ingrowth by native bone. The unsaturated polymer, PPF, was crosslinked in the presence of effervescent agents to yield a porous microstructure upon curing. An in vitro degradation study first assessed the temporal mechanical properties of the test material. This research was followed by an ex vivo study using a long-bone osteotomy model to characterize the mechanics of fixation. Results showed the initial compressive strength of the cross-linked PPF system was comparable to cancellous bone. The rate of strength loss was commensurate with the predicted mechanical recovery of healing bone with analogous results in a composite that comprised also 25% (by weight) autograft. Mechanical testing in the long-bone model demonstrated that PPF-based bone-graft substitute increased the flexural strength of K-wire stabilized osteotomies. These results suggest that this type of bone graft substitute may have clinical utility in the stabilization of complex tubular bone fractures.

Animals↗
PubMed2002

Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute.

STUDY DESIGN: Reviews were conducted. OBJECTIVES: To review the biology of spine fusion healing, and to outline several fundamental principles required for the selection of a bone graft substitute. SUMMARY OF BACKGROUND DATA: More than 200,000 spine fusions are performed each year in the United States. The success of this procedure is limited by morbidity from iliac crest bone graft harvest and a nonunion rate that ranges from 10% to 40%. In recent years, there has been an increased understanding of the biology of spine fusion healing. In addition, there has been a focus on finding suitable substitutes for autogenous iliac crest bone graft to promote spine fusion. The selection of a specific bone graft substitute can be a daunting task for the surgeon. METHODS: The available literature was reviewed and combined with the author's personal experience. RESULTS: A basic understanding of the biology of healing in different types of spine fusions and the differences between different categories of bone graft substitutes can help surgeons organize the graft selection process. CONCLUSIONS: In general, purely osteoconductive substitutes are less effective in adult posterolateral spine fusions, but may be suitable in the anterior spine when it is rigidly immobilized. Osteoinductive substitutes are more likely to be successful as extenders, enhancers, or substitutes for posterolateral spine fusion.

Animals↗
PubMed2006

Evaluation of allogeneic bone graft substitute for treatment of periodontal osseous defects: 6-month clinical results.

This article is an initial clinical evaluation of the use of Puros, a specially processed allogeneic bone graft substitute, for treatment of periodontal osseous defects. Nine patients with chronic periodontitis contributed 1 osseous defect each. Clinical and surgical measurements were taken at the time of the initial grafting and 6 months later at the time of a surgical re-entry. On average, probing depth improved by 3 mm, and there was 2.5 mm bone fill. Resorption of the alveolar crest was minimal. All cases healed satisfactorily, and at the time of re-entry only 1 case required re-treatment. Puros appears to be a useful and beneficial material for the treatment of proximal type human periodontal defects.

Bone Substitutes↗
PubMed2002

Hydroxyapatite/calcium carbonate (HA/CC) vs. plaster of Paris: a histomorphometric and radiographic study in a rabbit tibial defect model.

The search for an ideal bone substitute is ongoing. Multiple osteoconductive bone substitutes are available today. Plaster of Paris (POP) (calcium sulfate) has been used for more than 100 years for treatment of skeletal defects. This implant is compared to a new material, hydroxyapatite/calcium carbonate (HA/CC), in a rabbit tibia model. HA/CC is made from partial conversion of coralline calcium carbonate to hydroxyapatite and has an outer hydroxyapatite layer and an inner calcium carbonate core, a combination that leads to faster resorption than that of pure hydroxyapatite. This study compares the histomorphometric and radiographic properties of POP and HA/CC in a rabbit tibial defect. Both implants preferentially restore bone to the cortex relative to the canal. Plaster of Paris was fully resorbed by 6 weeks both radiographically and histometrically and HA/CC was substantially resorbed by 42 weeks. No significant difference was noted in volume fraction of bone between the two implants at 42 weeks postimplantation. Hydroxyapatite/calcium carbonate is a biocompatible bone graft substitute with a rate of resorption significantly slower than plaster of Paris.

Animals↗
PubMed2002

A composite bone graft substitute for anterior cervical fusion: assessment of osseointegration by quantitative computed tomography.

STUDY DESIGN: An ongoing prospective nonrandomized trial was conducted with 146 patients who underwent anterior cervical fusion with a bone graft substitute. The results for 78 patients followed up a minimum of 2 years are reported by an independent observer. OBJECTIVE: To investigate the clinical efficacy and osseointegration of the implant. SUMMARY OF BACKGROUND DATA: Most of the cervical cages provide an immediate load-bearing capacity, but not necessarily a solid fusion. The bony ingrowth can hardly be evaluated by flexion-extension plain radiographs, especially if a part of the implant is made of titanium. METHODS: The composite bone graft substitute consists of a rectangular fenestrated titanium cage filled with a highly porous hydroxyapatite cylinder soaked with bone marrow aspirated from a vertebra. Altogether, 102 implants were inserted for anterior cervical fusion. The bone ingrowth was measured in 50 patients by quantitative computed tomography of the implant and the adjacent vertebrae after 1 week, then 6 and 12 months after surgery. The investigation was repeated in 24 randomly selected patients 24 months after surgery. RESULTS: The surgery benefited 42 of 48 patients with myelopathy, 27 of 28 patients with radiculopathy, and both patients with anterior horn cell syndrome. No graft substitute-related complications were observed, and no revision surgery was performed. Six months after surgery, quantitative computed tomography showed up to a 14% increase in the hydroxyapatite mass in the core of the implant, which was statistically significant (P < 0.001). At 1 year, the newly formed hydroxyapatite mass increased to 23%, and in 2 years reached 24%. CONCLUSIONS: The composite implant is effective as a bone graft substitute, providing immediate load-bearing capacity, an osteoconductive scaffold, and osteoinductive potency. After surgery, the increase in hydroxyapatite radiodensity was apparent in plain computed tomography scans and confirmed to be significant by quantitative computed tomography.

Adult↗
PubMed2004

Bone tissue engineering: state of the art and future trends.

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.

Biocompatible Materials↗