Bone Implants and Induced Osteogenesis

Glowacki, Julie; Kaban, L. B.; Murray, JosephE.; Folkman, Judah; Mulliken, JohnB.

doi:10.1016/s0140-6736(82)91657-9

Cited by 6 publications

(2 citation statements)

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“…DBM has become widely accepted as a bone-graft substitute in clinical practice (18)(19)(20)(21)(22), but its bone inductive capacity has been questioned (23,24). In several studies, including our own, histology revealed that new bone was generated by osteoconduction rather than osteoinduction (25-27) -that is, bone regeneration occurred by growth of existing host bone on the DBM granules, which acted as a scaffold, rather than by de novo differentiation of bone, independent of pre-existing bone.…”

Section: Bmp and Demineralized Bone Matrixmentioning

confidence: 99%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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Recently, the first clinical reports on bone regeneration by two recombinant human bone morphogenetic proteins (rhBMPs), BMP-2 and BMP-7 (also named osteogenic protein-1, OP-1) have been published (1-4) . Although both BMPs were able to support bone regeneration, a significant variation in individual response was observed with both proteins. Animal studies and laboratory experiments reveal a number of conditions that influence the osteoinductivity of BMP, such as BMP concentration, carrier properties and influence of local and systemic growth factors and hormones. In this paper, these studies and the clinical reports are reviewed, and the conditions that modulate the BMP-dependent osteoinduction are discussed. The information may provide clues as to how the performance of recombinant human BMP as bone-graft substitute in humans can be improved. European Journal of Endocrinology 142 9-21 BMP and demineralized bone matrixThe history of bone morphogenetic proteins (BMPs) began with the observation that demineralized bone matrix (DBM) is able to induce ectopic bone formation in subcutaneous and intramuscular pockets in rodents (5, 6). This bone induction process has been studied extensively (7-13). Histological and biochemical analyses showed that cartilage appears 5-10 days after implantation of active DBM (8). This cartilage mineralizes by day 7-14 and is subsequently replaced by bone (7-9). After 21 days, haematopoietic bone marrow formation can be observed (12). These cellular events observed after DBM implantation mimic embryonic bone development and normal fracture repair (11). As DBM-related bone formation was observed to occur at ectopic sites, it was assumed that pluripotent mesenchymal cells are attracted to the site of implantation. Isolation of the bone-inducing substance revealed that certain proteins were responsible, which were termed bone morphogenetic proteins (BMPs) or osteogenetic proteins (OPs).The use of DBM in treating bone defects has proven beneficial for bone regeneration both in animals and in humans (14-17). DBM has become widely accepted as a bone-graft substitute in clinical practice (18-22), but its bone inductive capacity has been questioned (23, 24). In several studies, including our own, histology revealed that new bone was generated by osteoconduction rather than osteoinduction (25-27) -that is, bone regeneration occurred by growth of existing host bone on the DBM granules, which acted as a scaffold, rather than by de novo differentiation of bone, independent of pre-existing bone. Lack of inductive properties of DBM may be related to the procedures of production of commercially available DBM, as preservation of osteoinductive activity can be affected by the processing (28-30) or sterilization procedures (31). It is also possible that DBM of human origin, which is preferred for use in clinical practice, is less osteoinductive than DBM derived from animals, which is commonly used in animal studies. Several studies show that DBM from long-lived species such as baboon and human...

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Section: Bmp and Demineralized Bone Matrixmentioning

confidence: 99%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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“…These osteochondral progcnitor cells are present in the bone marrow stroma (3-6, 16,25,28,35) and can be isolated on the basis of their adherence to cell culture substrates under selccted medium conditions. When these culture-expanded cells are reimplanted into an appropriate in vivo environment, they differentiate into bone or cartilage, or both (S, 19,31,39,56). A subset of marrow-derived progenitor cells retains the ability to differentiate into bone (5.35).…”

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confidence: 99%

Osteochondral progenitor cells in acute and chronic canine nonunions

Boyan

Caplan

Heckman

et al. 1999

Journal Orthopaedic Research

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This study examined the ability of cells isolated from early healing segmental defects and from tissue from chronic nonunions to support bone and cartilage formation in vivo and their response to transforming growth factor-beta1 in vitro. Ostectomies (3 mm) were created in the radial diaphysis of four dogs. The dogs were splinted 3-5 days postoperatively and then allowed to bear full weight. At 7 days, tissue in the defect was removed and any periosteum was discarded; cells in the defect tissue were released by enzymatic digestion. The dogs were splinted again and allowed to bear full weight for 12 weeks. Radiographs confirmed a persistent nonunion in each dog. Defect tissue was again removed, any periosteum was discarded, and cells were isolated. Cells were also obtained from the defect tissue by nonenzymatic means with use of explant cultures. One-half of the tissue and one-half of any preconfluent, first-passage cultures were shipped to Cleveland by overnight carrier. At second passage, cells were loaded into ceramic cubes and implanted into immunocompromised mice for 3 or 6 weeks. Harvested cubes were examined histologically for cartilage and bone with use of a semiquantitative scoring system. Confluent fourth-passage cultures of 7 and 84-day defect tissue cells were cultured with 0.03-0.88 ng/ml transforming growth factor-beta1 for 24 hours, and [3H]thymidine incorporation and alkaline phosphatase specific activity were determined. Donor-dependent differences were noted in the rate at which defect cells achieved confluence; in general, cells from 7-day tissue divided most rapidly. Seven-day defect cells formed less bone and at a slower rate than was seen in the ceramic cubes containing samples from day 84. Cells derived enzymatically behaved similarly to those from explant cultures. Ceramic cubes contained fibrous connective tissue, cartilage, bone, and fat, indicating that multipotent cells were present. Stimulation of [3H]thymidine incorporation in response to transforming growth factor-beta1 was donor dependent and variable; only two of six separate isolates of cells exposed to it had measurable alkaline phosphatase activity (which was relatively low), and none of the cultures exhibited an increase in response to transforming growth factor-beta1 for 24 hours. This indicates that mesenchymal progenitor cells are present in the healing defect tissue at 7 and 84 days and that the relative proportion of osteochondroprogenitor cells is greater at the later time. The response to transforming growth factor-beta1 is typical of multipotent mesenchymal cells but not of committed chondrocytes or osteoblasts, indicating that these committed and differentiated cells are not present in early stages of healing and suggesting that their differentiation is inhibited in chronic nonunion.

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Kessler

Mayr-Wohlfart

Ignatius

et al. 2002

Journal of Materials Science: Materials in Medicine

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It was the purpose of this investigation to prove the biomechanical properties, the osteoconductive capacity and the degradation rate of alpha tricalcium phosphate (alpha TCP), a neutralized glass ceramics (GB9N) and a composite material (GB9N+copolymers). In a weight-bearing animal model six substitutes each were implanted in the medial tibial head of the right lower leg of adult Merino-sheep in a standardized surgical technique. After nine months the implants were harvested and prepared for histomorphological and histomorphometrical investigations (undecalcified Masson Goldner staining). For additional biomechanical testing of the specimens, non-operated bone blocks from the contralateral tibia as well as native implants served as controls. No significant differences for the maximum fracture load as well as for the yield strength were detected between harvested specimens and bone blocks from the contralateral tibia. However there were marked differences to ceramics that were not implanted. All substitutes showed osteoconduction, leading to a continuous ingrowth of new formed bone. However in the composite material soft tissue could be identified within the scaffold and there were signs of ongoing bone remodeling, nine months after implantation. The bone per tissue volume of alpha-TCP in conjunction to new bone (=percentage of trabecular bone volume plus percentage of residual substitute) was higher than for GB9N and the composite material. Nine months after implantation the percentage of residual alpha-TCP was 48%, it was 32% for GB9N and 28% for the composite. The intention of further studies should be to accelerate the degradation rates of substitutes and to improve biomechanical properties of implants by either modifying the chemical composition or combining materials with agents as, e.g. growth factors.

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Bone Implants and Induced Osteogenesis

Cited by 6 publications

References 0 publications

Bone morphogenetic proteins in human bone regeneration

Bone morphogenetic proteins in human bone regeneration

Osteochondral progenitor cells in acute and chronic canine nonunions

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