title: Visible-light-initiated hydrogels preserving cartilage extracellular signaling for inducing chondrogenesis of mesenchymal stem cells.
abstract: Hydrogels have a unique opportunity to regenerate damaged cartilage tissues by introducing mesenchymal stem cells (MSCs) in a highly swollen environment similar to articular cartilage. During cartilage development, collagen-cell interactions play an important role in mediating early mesenchymal condensation and chondrogenesis with transforming growth factor-β1 (TGF-β1) stimulation. Here, a hydrogel environment that can enhance cell-matrix interactions and chondrogenesis by stabilizing type-II collagen (Col II) and TGF-β1 into photopolymerizable (methacrylated) chitosan (MeGC) with simple entrapment and affinity binding is demonstrated. The MeGC hydrogel was designed to gel upon initiation by exposure to visible blue light in the presence of riboflavin, an aqueous initiator from natural vitamin. The incorporation of Col II into MeGC hydrogels increased cellular condensation and deposition of cartilaginous extracellular matrix by encapsulated chondrocytes. MeGC hydrogels containing Col II supported the release of TGF-β1 in a controlled manner over time in chondrogenic medium and the incorporated TGF-β1 further enhanced chondrogenesis of encapsulated chondrocytes and MSCs, especially synovial MSCs. Subcutaneous implantation of hydrogel cultures showed greatly improved neocartilage formation in constructs loaded with TGF-β1 compared with controls. These findings suggest that cartilage mimetic hydrogels have a high potential for cartilage repair.
authors.affiliation: Division of Advanced Prosthodontics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Bogyu
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Soyon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Advanced Prosthodontics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Diagnostic and Surgical Sciences, University of California, Los Angeles, CA 90095, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Bezouglaia
authors.affiliation: Department of Bio and Chemical Engineering, Hongik University, Sejong 339-701, Republic of Korea.
authors.forename: Jinku
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Evseenko
authors.affiliation: Division of Diagnostic and Surgical Sciences, University of California, Los Angeles, CA 90095, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Aghaloo
authors.affiliation: Division of Advanced Prosthodontics, University of California, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, CA 90095, USA. Electronic address: leemin@ucla.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D020219:Chondrogenesis; D020100:Hydrogels; D008027:Light; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D015398:Signal Transduction
chemical_list: D020100:Hydrogels
keywords: Chondrogenesis; Collagen; Mesenchymal stem cells; Photocrosslinkable chitosan hydrogels; Transforming growth factor