3 years ago

Multilayered pore-closed PLGA microsphere delivering OGP and BMP-2 in sequential release patterns for the facilitation of BMSCs osteogenic differentiation

Yan-Dong Mu, Ke Duan, Zhi-Wei Han, Bing-Jun Zhang, Jie Weng
Bone tissue regeneration may be more effectively administrated by controlled release of multiple biofactors, given that bone healing comprises a cascade of biological events controlled by numerous cytokines and growth factors (GFs). Here, we propose a novel microcarrier with the capability to sequentially deliver dual biofactors for better controlling the bone regeneration process. Firstly, osteogenic growth peptide (OGP) was incorporated in porous poly (lactic-co-glycolic) acid (PLGA) microspheres by a simple solution dipping method and subsequent pore-closing treatment. Then, a multilayered polyelectrolyte coating ((HA-CS)2-Hep-BMP-2-Hep-(CS-HA)2) was prepared on the surface of such OGP-loaded pore-closed PLGA microspheres by layer-by-layer assembly. Results showed that the OGP release was minimal (<17.1%) in the first 15 d but accelerated remarkably thereafter, while at least 60.3% of the BMP-2 load was released in the first 15 d and only very slow release was observed subsequently. Further in vitro cell experiments showed that the dual-biomolecule-loaded microspheres elicited more cells with extremely elongated cellular morphology, much higher alkaline phosphatase (ALP) level and up-regulated expression of osteocalcin (OCN). Such a dual loading of OGP and BMP-2 had a more positive impact on BMSCs proliferation and osteogenic differentiation compared with either OGP or BMP-2 alone, suggesting potential synergistic benefit of the sequential release of multiple peptide-based biofactors in a coordinated manner. Overall, this dual delivery system may provide a therapeutic strategy sequentially targeting multiple events (or mechanisms) during bone healing, which is believed to benefit the regenerative repair of bone defects. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jbm.a.36210

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