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Articles

Sustained delivery of BMP-2 enhanced osteoblastic differentiation of BMSCs based on surface hydroxyapatite nanostructure in chitosan–HAp scaffold

, , , , , & show all
Pages 1813-1827 | Received 22 Mar 2014, Accepted 31 Jul 2014, Published online: 28 Aug 2014
 

Abstract

The surface characteristics of biomaterials, especially regarding the sustained delivery of bone morphogenetic protein-2 (BMP-2), can possibly provide a novel and effective drug delivery system that can enhance osteogenesis. In this study, we evaluated the BMP-2 adsorption and release ability of the surface biomimetic hydroxyapatite (HAp) nanostructure on a new HAp-coated genipin-chitosan conjugation scaffold (HGCCS), and the resulting osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. HGCCS exhibited a loading efficiency of 65% (1.30 μg), which is significantly higher than 28% (0.56 μg, p < 0.01) for the genipin cross-linked chitosan framework, as quantified by an enzyme-linked immunosorbent assay. More importantly, we found that the release of BMP-2 from HGGCS sustained for at least 14 days in simulated body fluid in vitro, which is much better than the burst release within 3 days for CGF. Moreover, the BMP-2 release from HGCCS induced an increase in alkaline phosphatase activity as an indicator of osteogenic differentiation of seeded BMSCs for 14 days in vitro. HGCCS also stimulated a high mRNA expression of osteogenic differentiation makers, runt-related transcription factor 2 for 14 days, osteopontin for 3 days, and osteocalcin for 14 days. The results of this study suggest that the surface biomimetic HAp nanostructure of HGCCS used as a delivery system for BMP-2 is capable of promoting osteogenic differentiation in vitro. These findings demonstrated that HAp nanostructure assembled on organic porous scaffold could work as both calcium source and absorption/release platform, which opened a new research avenue for cell growth factor release, and provided a promising strategy for design and preparation of bioactive scaffold for bone tissue engineering.

Additional information

Funding

Funding. This research was supported by an NSFC (NSFDYS: 50925205, 31070735, 81102229, 51002089,IRG: 51321091), the Program of Introducing Talents of Discipline to Universities in China (111 program, No. b06015), the Natural Science Foundation of Shandong Province (ZR2010CZ004).

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