title: Release characteristics and osteogenic activity of recombinant human bone morphogenetic protein-2 grafted to novel self-assembled poly(lactide-co-glycolide fumarate) nanoparticles.
abstract: Functionalized biodegradable nanoparticles (NPs) provide reactive groups and large surface area for grafting recombinant human bone morphogenetic protein-2 (rhBMP-2) to reduce protein diffusion and maintain sufficient concentration for recruitment and differentiation of osteoprogenitor cells. The objective of this work was to investigate release characteristics and osteogenic activity of rhBMP-2, grafted to biodegradable NPs based on succinimide-terminated poly(lactide fumarate) (PLAF-NHS) and poly(lactide-co-glycolide fumarate) (PLGF-NHS) macromers. The release of rhBMP-2 from the NPs, measured by enzyme-linked immunosorbent assay, was linear with time in the first two weeks, and 24.70+/-1.30% and 48.7+/-0.7% of the protein grafted to PLGF-NHS and PLAF-NHS NPs, respectively, was released in the enzymatically active conformation after complete degradation/erosion of the NPs. After 14 days of incubation with bone marrow stromal (BMS) cells, rhBMP-2 grafted to PLAF-NHS and PLGF-NHS NPs was as effective in inducing mineralization as the native rhBMP-2 that was directly added to the cell culture media. At any incubation time, rhBMP-2 grafted to PLAF had the highest expression of osteopontin (OP) and osteocalcin (OC), followed by rhBMP-2 grafted to PLGF and rhBMP-2 directly added to media. Higher OP and OC expression for BMP-gPLAF and BMP-gPLGF groups may be related to other factors in the cascade of osteogenesis, such as differentiation of BMS cells to the vasculogenic lineage and formation of a vascularized/mineralized matrix.
authors.affiliation: Biomimetic Materials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Angel E
authors.initials: AE
authors.lastname: Mercado
authors.forename: Junyu
authors.initials: J
authors.lastname: Ma
authors.forename: Xuezhong
authors.initials: X
authors.lastname: He
authors.forename: Esmaiel
authors.initials: E
authors.lastname: Jabbari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007700:Kinetics; D008297:Male; D053758:Nanoparticles; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011091:Polyesters; D011994:Recombinant Proteins; C506897:Spp1 protein, rat; D015675:Osteocalcin; D053495:Osteopontin
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