Student Award for Outstanding Research Winner in the Ph.D. Category for the 9th World Biomaterials Congress, Chengdu, China, June 1‐5, 2012

Abstract

AbstractAs an initial step in the development of a bone tissue engineering strategy to rationally control inflammation, we investigated the interplay of bone‐like extracellular matrix (ECM) and varying doses of the inflammatory cytokine tumor necrosis factor alpha (TNF‐α) on osteogenically differentiating mesenchymal stem cells (MSCs) cultured in vitro on 3D poly(ε‐caprolactone) (PCL) microfiber scaffolds containing pregenerated bone‐like ECM. To generate the ECM, PCL scaffolds were seeded with MSCs and cultured in medium containing the typically required osteogenic supplement dexamethasone. However, since dexamethasone antagonizes TNF‐α, the interplay of ECM and TNF‐α was investigated by culturing naïve MSCs on the decellularized scaffolds in the absence of dexamethasone. MSCs cultured on ECM‐coated scaffolds continued to deposit mineralized matrix, a late stage marker of osteogenic differentiation. Mineralized matrix deposition was not adversely affected by exposure to TNF‐α for 4–8 days, but was significantly reduced after continuous exposure to TNF‐α over 16 days, which simulates the in vivo response, where brief TNF‐α signaling stimulates bone regeneration, while prolonged exposure has damaging effects. This underscores the exciting potential of PCL/ECM constructs as a more clinically realistic in vitro culture model to facilitate the design of new bone tissue engineering strategies that rationally control inflammation to promote regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.