Delivery of bone morphogenetic proteins for orthopedic tissue regeneration

Seeherman, Howard; Wozney, John M.

doi:10.1016/j.cytogfr.2005.05.001

Cited by 350 publications

(266 citation statements)

References 146 publications

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“…Most BMPs have the capacity to promote endochondral ossification whereby cartilage formation is induced but replaced by bone, particularly in the presence of multipotent progenitor cells. Thus, BMPs may serve as better therapeutic agents for fracture repair than for the repair of cartilage (23).…”

Section: Mary B Goldringmentioning

confidence: 99%

Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

Goldring

2006

Arthritis & Rheumatism

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Section: Mary B Goldringmentioning

confidence: 99%

Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

Goldring

2006

Arthritis & Rheumatism

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“…OP-1™ (BMP-7, Olympus, Stryker) or BMP-2 (Infuse Bone Graft, Medtronic, Minneapolis). Numerous studies have explored synthetic polymers, naturally-derived materials, and calcium phosphates in formats including gels, injectable liquids, scaffolds, and particles [2][3][4][5][6]. Despite this body of work, high concentrations of rhBMPs are still needed for effective therapies.…”

Section: Introductionmentioning

confidence: 99%

N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

Karfeld-Sulzer

Ghayor

Siegenthaler

et al. 2015

Journal of Controlled Release

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Bone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50 mol% lactide performed better than the one having 75 mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration. ABSTRACTBone morphogenetic proteins (BMPs) are growth and differentiation factors involved during development in morphogenesis, organogenesis and later mainly in regeneration processes, in particular in bone where they are responsible for osteoinduction. For more than a decade, recombinant human (rh)BMP-2 has been used in the clinic for lumbar spinal fusion at non-physiological high dosages that appear to be causative for side effects, like male sterility. A possible strategy to reduce the effective amount of rhBMP-2 in the clinic is the co-delivery with an enhancer of BMPs' activity. In an earlier study, we showed that N-methylpyrrolidone (NMP) enhances BMP activity in vitro and in vivo. Here we report on the development of a slow and sustained double delivery of rhBMP-2 and NMP via an in situ forming implant based on poly(lactide-co-glycolide). The results showed that the release of NMP can be adjusted by varying the lactide/glycolide ratio and the polymer's molecular weight. The same applied to rhBMP-2, with release rates that could be sustained from two to three weeks. In the in vivo model of a critical size defect in the calvarial bone of rabbits, the implant containing 50 mol% lactide performed better than the one having 75 mol% lactide in terms of defect bridging and extent of bony regenerated area. In situ forming implants for the double delivery of the BMP enhancer NMP and rhBMP-2 appear to be promising delivery systems in bone regeneration.

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“…For cytokine therapy, an appropriate carrier material is needed that retains BMP and releases it slowly, while serving as a scaffold for new bone formation [28,29]. Several materials have already been evaluated as BMP carriers, including collagen obtained from animal sources [3,11,13,31], synthetic polymers [14,15,19], tricalcium phosphate [17], and other inorganic materials [16].…”

Section: Introductionmentioning

confidence: 99%

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

Nanno

Sugiyasu

Daimon

et al. 2009

Clin Orthop Relat Res

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Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA-PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 lg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dosedependent manner after the implantation of DC alginate, atelocollagen, and PLA-PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field.

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Delivery of bone morphogenetic proteins for orthopedic tissue regeneration

Cited by 350 publications

References 146 publications

Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

N-methyl pyrrolidone/bone morphogenetic protein-2 double delivery with in situ forming implants

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

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