title: Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds.
abstract: In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy.
authors.affiliation: Department of Stomatology, the 4th Affiliated Hospital of China Medical University, Shenyang, Liaoning, China; Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Stomatology, the 4th Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oral Biology, The State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004195:Disease Models, Animal; D017886:Durapatite / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000473:pathology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D048271:Chitosan; D017886:Durapatite
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