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Chondrogenesis of hMSC in affinity-bound TGF-beta scaffolds

Paper ID Volume ID Publish Year Pages File Format Full-Text
7040 530 2012 11 PDF Available
Title
Chondrogenesis of hMSC in affinity-bound TGF-beta scaffolds
Abstract

Herein we describe a bio-inspired, affinity binding alginate-sulfate scaffold, designed for the presentation and sustained release of transforming growth factor beta 1 (TGF-β1), and examine its effects on the chondrogenesis of human mesenchymal stem cells (hMSCs). When attached to matrix via affinity interactions with alginate sulfate, TGF-β1 loading was significantly greater and its initial release from the scaffold was attenuated compared to its burst release (>90%) from scaffolds lacking alginate-sulfate. The sustained TGF-β1 release was further supported by the prolonged activation (14 d) of Smad-dependent (Smad2) and Smad-independent (ERK1/2) signaling pathways in the seeded hMSCs. Such presentation of TGF-β1 led to hMSC chondrogenic differentiation; differentiated chondrocytes with deposited collagen type II were seen within three weeks of in vitro hMSC seeding. By contrast, in scaffolds lacking alginate-sulfate, the effect of TGF-β1 was short-term and hMSCs could not reach a similar differentiation degree. When hMSC constructs were subcutaneously implanted in nude mice, chondrocytes with deposited type II collagen and aggrecan typical of the articular cartilage were found in the TGF-β1 affinity-bound constructs. Our results highlight the fundamental importance of appropriate factor presentation to its biological activity, namely - inducing efficient stem cell differentiation.

Keywords
Affinity-binding; Alginate-sulfate; Alginate scaffold; Chondrogenesis; Human mesenchymal stem cells; TGF-beta1
First Page Preview
Chondrogenesis of hMSC in affinity-bound TGF-beta scaffolds
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 3, January 2012, Pages 751–761
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering