Healing Bone Using Recombinant Human Bone Morphogenetic Protein 2 and Copolymer

Kirker‐Head, Carl A.; Gerhart, Tobin N.; Armstrong, R. M.; Schelling, Scott H.; Carmel, Laura A.

doi:10.1097/00003086-199804000-00026

Cited by 123 publications

(75 citation statements)

References 34 publications

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“…Yasko and coworkers (96) reported healing of femur defects by rhBMP-2 in rats. In sheep, femoral defects showed new bone formation 1 month after grafting with rhBMP-2, and complete radiographic bone union was observed 3 months after grafting; 1 year after grafting, histology showed the presence of woven and lamellar bone (97). In dogs, mandibular defects were restored by rhBMP-2 within 3 months.…”

Section: Bone Healing In Animal Studies Using Bmpmentioning

confidence: 96%

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: Bone Healing In Animal Studies Using Bmpmentioning

confidence: 96%

Bone morphogenetic proteins in human bone regeneration

Groeneveld

Burgér

2000

European Journal of Endocrinology

358

217

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“…At present, only BMP-2 and BMP-7 are produced commercially as a therapy to enhance bone healing with BMP-7 called osteogenic protein 1 (OP-1). BMP-2 and OP-1 both promote bone formation in a variety of experimental models (rat [8,13,25,46,47,56], rabbit [3,10,29,48], sheep [15,20], dog [9,19,32,35,40,43]). Although these proteins are now used clinically, most of the information on their effects is known from these and other experimental studies.…”

Section: Introductionmentioning

confidence: 99%

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

Gilley

Wallace

Bourgeault

et al. 2009

Clin Orthop Relat Res

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Glucocorticoids inhibit bone remodeling and fracture healing. We sought to determine whether osteogenic protein 1 (OP-1) can overcome this inhibition in a closed fracture model in the rat. Time-released prednisolone or placebo pellets were implanted subcutaneously; closed femoral fractures were created 2 weeks later in rats. Fractures received sham, OP-1 and collagen, or collagenonly implants. Femurs were harvested at 3, 10, 21, 28, and 42 days postfracture. Fractures were examined radiographically for amount of hard callus; mechanically for torque and stiffness (also expressed as a percentage of the contralateral intact femur); and histomorphometrically for amount of cartilaginous and noncartilaginous soft callus, hard callus, and total callus. Glucocorticoid administration inhibited fracture healing. The application of a devitalized Type I collagen matrix mitigated the inhibitory effects of prednisolone on fracture healing However, further increases in indices of fracture healing were observed when OP-1 was added to the collagen matrix compared with collagen alone. OP-1 and collagen was more effective than collagen alone.

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“…Sheep were used in this experiment because of their similar hip anatomy to humans, and because of their size which allows perform surgical procedures used in humans 25 . These features make the sheep a good model for studies in orthopedic surgery.…”

Section: Discussionmentioning

confidence: 99%

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results

Feitosa¹,

Fadel²,

Beltrão-Braga³

et al. 2010

Acta Cir. Bras.

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PURPOSE: Evaluate the bone tissue recovery following transplantation of ovine mesenchymal stem cells (MSC) from bone marrow and human immature dental-pulp stem cells (hIDPSC) in ovine model of induced osteonecrosis of femoral head (ONFH). METHODS: Eight sheep were divided in three experimental groups. First group was composed by four animals with ONFH induced by ethanol through central decompression (CD), for control group without any treatment. The second and third group were compose by two animals, six weeks after ONFH induction received transplantation of heterologous ovine MSC (CD + oMSC), and hIDPSC (CD + hIDPSC), respectively. In both experiments the cells were transplanted without application of any type of immunosupression protocol. RESULTS: Our data indicate that both cell types used in experiments were able to proliferate within injured site providing bone tissue recovery. The histological results obtained from CD+hIDPSC suggested that the bone regeneration in such animals was better than that observed in CD animals. CONCLUSION: Mesenchymal stem cell transplant in induced ovine osteonecrosis of femoral head by central decompression technique is safe, and apparently favors bone regeneration of damaged tissues.

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Healing Bone Using Recombinant Human Bone Morphogenetic Protein 2 and Copolymer

Cited by 123 publications

References 34 publications

Bone morphogenetic proteins in human bone regeneration

Bone morphogenetic proteins in human bone regeneration

OP-1 Augments Glucocorticoid-inhibited Fracture Healing in a Rat Fracture Model

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results

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