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Incorporation of an aggrecan mimic prevents proteolytic degradation of anisotropic cartilage analogs

Paper ID Volume ID Publish Year Pages File Format Full-Text
915 69 2013 8 PDF Available
Title
Incorporation of an aggrecan mimic prevents proteolytic degradation of anisotropic cartilage analogs
Abstract

Biomimetic scaffolds that promote regeneration and resist proteolysis are required as a tissue engineering solution to repair or replace a broad range of diseased tissues. Native corrosive environments, such as the richly enzymatic milieu of diseased articular cartilage, degrade the local extracellular matrix structure, so an implantable replacement must both replicate the healthy structure and demonstrate substantial proteolytic immunity, yet promote regeneration, if long-term functional success is to be achieved. Here, we combine magnetically aligned collagen with peptidoglycans, biosynthetic molecules that mimic proteoglycan activity but lack core proteins susceptible to proteases, to develop cartilage scaffold analogs with tailored functionality. With the incorporation of the aggrecan mimic, we demonstrate an ability to enhance bulk mechanical properties and prevent cytokine-induced degradation. Furthermore, fiber alignment in collagen scaffolds enhanced the gene expression of aggrecan, indicating cell responsiveness to anisotropy that also better replicates the natural environment of cartilage. Finally, the expression of type II collagen is enhanced with both alignment and incorporation of the aggrecan mimic, showing synergism between fiber alignment and incorporation of the aggrecan mimic. The work presented here identified a mechanistic synergy of matrix molecules and organization to prevent proteolysis while simultaneously upregulating protein expression.

Keywords
Articular cartilage regeneration; Inflammation; Magnetically aligned collagen; Peptidoglycans; Proteolysis
First Page Preview
Incorporation of an aggrecan mimic prevents proteolytic degradation of anisotropic cartilage analogs
Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 9, Issue 1, January 2013, Pages 4618–4625
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering