Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinductionin vivo

Abstract

Bone morphogenetic proteins (BMP) are unique molecules with a specific biological activity for inducing ectopic bone formation when implanted with a suitable carrier matrix. However, incorporation of BMP into the carrier has disadvantages, including early burst release and protein degradation in biological environments. Therefore, we considered that the next greatest challenge in achieving successful clinical use was the development of a carrier system for site-specific delivery of the morphogenetic signal of BMP. In this study, a novel BMP-2-derived oligopeptide, NSVNSKIPKACCVPTELSAI, was coupled covalently to alginate. Then NSVNSKIPKACCVPTELSAI-linked alginate hydrogel composites were implanted into the calf muscle of rats and harvested 3 or 8 weeks after surgery. Ectopic bone formation was observed in alginate hydrogel linked with BMP-2-derived peptide. It is suggested that alginate hydrogel linked with an oligopeptide derived from BMP-2 might provide an alternative system for topical delivery of the morphogenetic signal of BMP-2.

Controlled differentiation of stem cells

“…Delivery of growth factors for morphogenesis and differentiation of stem cells have been successfully verified in various biomaterials [92]. Growth factors have been covalently modified on the surface of biomaterials to provide progrowth and pro-survival factors which may enhance long-term in vivo survival and differentiation of stem cells [93,94]. Growth factors released from biomaterials via diffusion, cell-mediated proteolysis, or in response to mechanical stimuli have been successfully incorporated for in vitro and in vivo regenerative applications [92,95].…”

Studies on thePinctada fucataBMP-2 Gene: Structural Similarity and Functional Conservation of Its Osteogenic Potential within the Animal Kingdom

“…Previous reports showed that a synthetic peptide corresponding to residues 68-87 (NSVNSKIPKACCVPTELSAI) of the knuckle epitope of human BMP-2 could induce ectopic bone formation in vivo [21,22], suggesting that this sequence is the functional domain of the mature human BMP-2. Another study identified that a peptide corresponding to amino acids 73-92 (KIPKASSVPTELSAISTLYL) of human BMP-2, which substituted Cys78, Cys79, and Met89 with Ser (S), Ser (S), and Thr (T), respectively, induced a higher alkaline phosphatase (ALP) activity than the original 68-87 peptide [22].…”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…De Mel et al have recently published a review on biofunctionalization of biomaterials for accelerated in situ endothelialization (de Mel et al, 2008). Not only complete GFs can be attached to scaffold surfaces, but also oligopeptides such as those derived from BMP-2 or BMP-7 that have been immobilized on alginate hydrogels and glass, respectively (Kirkwood et al, 2003;Saito et al, 2003;Suzuki et al, 2000). These in vitro studies, performed with a murine multipotent MSC culture or with primary rat calvarial osteoblastic cell populations showed that immobilized oligopeptides may have the capacity to induce osteoblastic differentiation and mineralization in a more predictable manner than the entire GF.…”

“…This might be attributed to the lower complexity of the molecule and therefore increased stability. Implantation of a BMP-2 derived oligopeptide covalently coupled to alginate into the calf muscle of rats resulted in ectopic bone formation (Suzuki et al, 2000). Synthetic peptide mimics have also been applied for the promotion of angiogenic responses (X.…”