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Development of a Cellularly Degradable PEG Hydrogel to Promote Articular Cartilage Extracellular Matrix Deposition
Author(s) -
Sridhar Balaji V.,
Brock John L.,
Silver Jason S.,
Leight Jennifer L.,
Randolph Mark A.,
Anseth Kristi S.
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201400695
Subject(s) - extracellular matrix , scaffold , cartilage , tissue engineering , chondrogenesis , self healing hydrogels , biomedical engineering , materials science , microbiology and biotechnology , chemistry , mesenchymal stem cell , population , biochemistry , anatomy , medicine , biology , environmental health , polymer chemistry
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.