title: Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.
abstract: Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene hydrogel is functionalized with thiolated transforming growth factor (TGF-β1) and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated with a smaller population of mesenchymal stem cells, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. The co-encapsulated cells cleave the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly degraded materials show significantly increased glycosaminoglycan and collagen deposition over just 14 d of culture, while maintaining high levels of viability and producing a more widely-distributed matrix. These results indicate the potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications.
authors.affiliation: Department of Chemical and Biological Engineering and the Biofrontiers Institute, University of Colorado, 596 UCB, Boulder, CO, 80303-0596, USA.
authors.forename: Balaji V
authors.initials: BV
authors.lastname: Sridhar
authors.forename: John L
authors.initials: JL
authors.lastname: Brock
authors.forename: Jason S
authors.initials: JS
authors.lastname: Silver
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Leight
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D018920:Coculture Techniques; D003094:Collagen; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D053773:Transforming Growth Factor beta1
chemical_list: D020100:Hydrogels; D053773:Transforming Growth Factor beta1; D011092:Polyethylene Glycols; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: cartilage; chondrocytes; growth factor; matrix metalloproteinases; mesenchymal stem cells; tissue engineering