Peer-Reviewed Journal Details
Mandatory Fields
Ansboro, S;Hayes, JS;Barron, V;Browne, S;Howard, L;Greiser, U;Lalor, P;Shannon, F;Barry, FP;Pandit, A;Murphy, JM
2014
April
Journal Of Controlled Release
A chondromimetic microsphere for in situ spatially controlled chondrogenic differentiation of human mesenchymal stem cells
Published
Altmetric: 2WOS: 17 ()
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PHARMACOLOGICALLY ACTIVE MICROCARRIERS HYALURONIC-ACID HYDROGELS MURINE KNEE-JOINT FACTOR-BETA 3 EXTRACELLULAR-MATRIX TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSIENT EXPOSURE PLGA MICROSPHERES INTRAARTICULAR INJECTIONS PROTEOGLYCAN SYNTHESIS
179
42
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Human mesenchymal stem cells (hMSCs) have been identified as a viable cell source for cartilage tissue engineering. However, to undergo chondrogenic differentiation hMSCs require growth factors, in particular members of the transforming growth factor beta (TGF-beta) family. While in vitro differentiation is feasible through continuous supplementation of TGF-beta 3, mechanisms to control and drive hMSCs down the chondrogenic lineage in their native microenvironment remain a significant challenge. The release of TGF-beta 3 from an injectable microsphere composed of the cartilage-associated extracellular matrix molecule hyaluronan represents a readily translatable approach for in situ differentiation of hMSCs for cartilage repair. In this study, chondromimetic hyaluronan microspheres were used as a growth factor delivery source for hMSC chondrogenesis. Cellular compatibility of the microspheres (1.2 and 14.1 mu m) with hMSCs was shown and release of TGF-beta 3 from the most promising 14.1 mu m microspheres to control differentiation of hMSCs was evaluated. Enhanced accumulation of cartilage-associated glycosaminoglycans by hMSCs incubated with TGF-beta 3-loaded microspheres was seen and positive staining for collagen type II and proteoglycan confirmed successful in vitro chondrogenesis. Gene expression analysis showed significantly increased expression of the chondrocyte-associated genes, collagen type II and aggrecan. This delivery platform resulted in significantly less collagen type X expression, suggesting the generation of a more stable cartilage phenotype. When evaluated in an ex vivo osteoarthritic cartilage model, implanted hMSCs with TGF-beta 3-loaded HA microspheres were detected within cartilage fibrillations and increased proteoglycan staining was seen in the tissue. In summary, data presented here demonstrate that TGF-beta 3-bound hyaluronan microspheres provide a suitable delivery system for induction of hMSC chondrogenesis and their use may represent a clinically feasible tissue engineering approach for the treatment of articular cartilage defects. (C) 2014 Elsevier B.V. All rights reserved.
0168-3659
10.1016/j.jconrel.2014.01.023
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