title: A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition.
abstract: Articular cartilage remains a significant clinical challenge to repair because of its limited self-healing capacity. Interest has grown in the delivery of autologous chondrocytes to cartilage defects, and combining cell-based therapies with scaffolds that capture aspects of native tissue and allow cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold often does not match the rate of matrix production by chondrocytes, which can limit functional tissue regeneration. Here, we designed a hybrid biosynthetic system consisting of poly (ethylene glycol) (PEG) endcapped with thiols and crosslinked by norbornene-functionalized gelatin via a thiol-ene photopolymerization. The protein crosslinker was selected to facilitate chondrocyte-mediated scaffold remodeling and matrix deposition. Gelatin was functionalized with norbornene to varying degrees (~4-17 norbornenes/gelatin), and the shear modulus of the resulting hydrogels was characterized (<0.1-0.5 kPa). Degradation of the crosslinked PEG-gelatin hydrogels by chondrocyte-secreted enzymes was confirmed by gel permeation chromatography. Finally, chondrocytes encapsulated in these biosynthetic scaffolds showed significantly increased glycosaminoglycan deposition over just 14 days of culture, while maintaining high levels of viability and producing a distributed matrix. These results indicate the potential of a hybrid PEG-gelatin hydrogel to permit chondrocyte-mediated remodeling and promote articular cartilage matrix production. Tunable scaffolds that can easily permit chondrocyte-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado; BioFrontiers Institute, University of Colorado, Boulder, Colorado.
authors.forename: Balaji V
authors.initials: BV
authors.lastname: Sridhar
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Dailing
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado; BioFrontiers Institute, University of Colorado, Boulder, Colorado.
authors.forename: J Logan
authors.initials: JL
authors.lastname: Brock
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado; Department of Craniofacial Biology, School of Dental Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Stansbury
authors.affiliation: Department of Orthopedic Surgery, Laboratory for Musculoskeletal Tissue Engineering, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Plastic Surgery Research Laboratory, Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado; BioFrontiers Institute, University of Colorado, Boulder, Colorado; Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado.
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth