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The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities

Paper ID Volume ID Publish Year Pages File Format Full-Text
10125 666 2008 8 PDF Available
Title
The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities
Abstract

A thiol–acrylate photopolymerization was used to incorporate enzymatically cleavable peptide sequences into PEG hydrogels to induce chondrogenic differentiation of encapsulated human mesenchymal stem cells (hMSCs). An adhesive sequence, RGD, was designed with an MMP-13 specific cleavable linker. RGD promotes survival of hMSCs encapsulated in PEG gels and has shown to induce early stages of chondrogenesis, while its persistence can limit complete differentiation. Therefore, an MMP-13 cleavage site was incorporated into the peptide sequence to release RGD mimicking the native differentiation timeline. Active MMP-13 production of encapsulated hMSCs was seen to increase from day 9 to 14 and only in chondrogenic differentiating cultures. Seeded hMSCs attached to the material prior to enzymatic cleavage, but a significant population of the cells detach after cleavage and release of RGD. Finally, hMSCs encapsulated in RGD-releasing gels produce 10 times as much glycosaminoglycan as cells with uncleavable RGD functionalities, by day 21 of culture. Furthermore, 75% of the cells stain positive for collagen type II deposition where RGD is cleavable, as compared to 19% for cultures where RGD persists. Collectively, these data provide evidence that temporal regulation of integrin-binding peptides is important in the design of niches in differentiating hMSCs to chondrocytes.

Keywords
Human mesenchymal stem cells; RGD; Collagenase-3; Chondrogenesis
First Page Preview
The enhancement of chondrogenic differentiation of human mesenchymal stem cells by enzymatically regulated RGD functionalities
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 15, May 2008, Pages 2370–2377
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering