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2013   Volume No 25 – pages 114-129

Title: Effect of scaffold microarchitecture on osteogenic differentiation of human mesenchymal stem cells

Author: A Phadke, Y Hwang, S Hee Kim, S Hyun Kim, T Yamaguchi, K Masuda, S Varghese

Address: Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, MC 0412, La Jolla, CA 92093, USA

E-mail: svarghese at ucsd.edu

Key Words: Mesenchymal stem cells; synthetic grafts; spongy cryogels; columnar cryogels; osteoblastic genes; bone formation.

Publication date: January 18th 2013

Abstract: Design of macroporous synthetic grafts that can promote infiltration of cells, their differentiation, and synthesis of bone-specific extracellular matrix is a key determinant for in vivo bone tissue regeneration and repair. In this study, we investigated the effect of the microarchitecture of the scaffold on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Poly(ethylene glycol) diacrylate-co-N-acryloyl 6-aminocaproic acid cryogels were fabricated to have either a pore network consisting of cellular, randomly oriented pores (termed ‘spongy’) or a pore network consisting of lamellar columns (termed ‘columnar’), with both cryogel types showing a similar porosity. Both spongy and columnar cryogels supported comparable levels of cell viability and proliferation of hMSCs in vitro. However, spongy cryogels promoted osteogenic differentiation to a greater extent than their columnar counterparts, as evidenced by increased alkaline phosphatase activity and osteoblastic gene expression over 21 days post culture. Leveraging upon our previous work, we further evaluated the ability of these synthetic scaffolds in conjunction with mineralisation to promote ectopic bone formation upon subcutaneous implantation in nude rats. Mineralised spongy and columnar cryogels, both in the presence and absence of exogenous hMSCs, promoted ectopic bone formation in vivo. No such bone formation was observed in acellular cryogels devoid of mineralisation, with extensive host cell infiltration and vascularisation in columnar cryogels, and negligible infiltration into spongy cryogels. Our results thus present a novel method to tune the microarchitecture of porous polymeric scaffolds, in addition to suggesting their efficacy as synthetic bone grafts.

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Last modified January 18, 2013

Open Access / Author retains copyright

AO Foundation, Davos, Switzerland