title: A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate.
abstract: The development of hydrogels tailored for cartilage tissue engineering has been a research and clinical goal for over a decade. Directing cells towards a chondrogenic phenotype and promoting new matrix formation are significant challenges that must be overcome for the successful application of hydrogels in cartilage tissue therapies. Gelatin-methacrylamide (Gel-MA) hydrogels have shown promise for the repair of some tissues, but have not been extensively investigated for cartilage tissue engineering. We encapsulated human chondrocytes in Gel-MA-based hydrogels, and show that with the incorporation of small quantities of photocrosslinkable hyaluronic acid methacrylate (HA-MA), and to a lesser extent chondroitin sulfate methacrylate (CS-MA), chondrogenesis and mechanical properties can be enhanced. The addition of HA-MA to Gel-MA constructs resulted in more rounded cell morphologies, enhanced chondrogenesis as assessed by gene expression and immunofluorescence, and increased quantity and distribution of the newly synthesized extracellular matrix (ECM) throughout the construct. Consequently, while the compressive moduli of control Gel-MA constructs increased by 26 kPa after 8 weeks culture, constructs with HA-MA and CS-MA increased by 114 kPa. The enhanced chondrogenic differentiation, distribution of ECM, and improved mechanical properties make these materials potential candidates for cartilage tissue engineering applications.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia; Department of Orthopaedics, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Levett
authors.forename: Ferry P W
authors.initials: FP
authors.lastname: Melchels
authors.forename: Karsten
authors.initials: K
authors.lastname: Schrobback
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Klein
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D055119:Elastic Modulus / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005780:Gelatin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008027:Light; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D055114:X-Ray Microtomography
chemical_list: D006025:Glycosaminoglycans; D005780:Gelatin; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates
keywords: Cartilage tissue engineering; Gelatin; Hyaluronic acid; Hydrogels; Photopolymerization