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

Abstract

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.

Root surface conditioning with bone morphogenetic protein-2 facilitates cementum-like tissue deposition in beagle dogs

“…Although gingival connective tissue proliferates and/or attaches to the root surface, osteogenic modification of the root may initially acquire new and well‐established attachment to gingival connective tissue, and consequently inhibition of epithelial downgrowth may be elevated. BMPs have the ability to transform pluripotent stem cells into osteoprogenitor cells (9) and induce ectopic osteogenesis (10,11). Zaman et al.…”

Enhancement of recombinant human BMP‐7 bone formation with bmp binding peptide in a rodent femoral defect model

“…12 Therefore, an effective carrier must be used to achieve a localized effect at the desired bone healing site. BMP carriers can be classified as naturally occurring polymers, 13,14 synthetic polymers, 15 composites of synthetic and naturally occurring polymers, 8 and inorganic salts. 16 Bovine bonederived type I collagen is used as a carrier to bind rhBMP-7 in the clinical setting.…”

“…Therefore, several strategies were developed to lower the dose of BMPs, which may decrease the dose-related complications, but achieve similar or more efficacious healing. These strategies include the use of delivery devices that allow better application of rhBMP-7 and obtain better retention at the surgery site, 7 the use of carriers that control the release of rhBMP-7, 8 and the use of a specific binding peptide that enhances the effect of rhBMP-2 in bone healing. 9 BMP binding peptide (BBP) was developed by Behnam et al 10 They isolated an 18.5 kDa fragment of the human bone matrix protein that has the chemical and physical properties of Urist's ''BMP.''…”

Tissue Engineering of a Vascularized Bone Graft of Critical Size with an Osteogenic and Angiogenic Factor-Based In Vivo Bioreactor

“…13,14 They may induce mesenchymal stem cells to differentiate into osteoblasts, consequently resulting in bone formation on an ectopical site. [15][16][17] Our previous studies showed that a large recombinant human bone morphogenetic protein-7 (rhBMP-7)-loaded natural bovine bone mineral (NBBM) scaffold, once having been placed in the muscles of a miniature pig, was ossified and vascularized after 12 weeks. 10,[18][19][20] In the same way, we successfully cultivated a vascularized bone graft with custom shape in the latissimus dorsi muscle in a patient of subtotal mandible defect, which was caused by tumor resection.…”