title: Chondrocyte redifferentiation and construct mechanical property development in single-component photocrosslinkable hydrogels.
abstract: Hydrogels are promising materials for cartilage repair, but the properties required for optimal functional outcomes are not yet known. In this study, we functionalized four materials that are commonly used in cartilage tissue engineering and evaluated them using in vitro cultures. Gelatin, hyaluronic acid, polyethylene glycol, and alginate were functionalized with methacrylic anhydride to make them photocrosslinkable. We found that the responses of encapsulated human chondrocytes were highly dependent on hydrogel type. Gelatin hydrogels supported cell proliferation and the deposition of a glycosaminoglycan rich matrix with significant mechanical functionality. However, cells had a dedifferentiated phenotype, with high expression of collagen type I. Chondrocytes showed the best redifferentiation in hyaluronic acid hydrogels, but the newly formed matrix was highly localized to the pericellular regions, and these gels degraded rapidly. Polyethylene glycol hydrogels, as a bioinert control, did not promote any strong responses. Alginate hydrogels did not support the deposition of new matrix, and the stiffness decreased during culture. The markedly different response of chondrocytes to these four photocrosslinkable hydrogels demonstrates the importance of material properties for chondrogenesis and extracellular matrix production, which are critical for effective cartilage repair.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia; Department of Orthopaedics, University Medical Center, P.O. 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: D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D048430:Cell Shape / Q000187:drug effects / Q000528:radiation effects; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019245:Compressive Strength / Q000187:drug effects / Q000528:radiation effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D008027:Light; D055595:Mechanical Phenomena / Q000187:drug effects* / Q000528:radiation effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D020100:Hydrogels
keywords: cartilage; chondrogenesis; hydrogels; photopolymerization; tissue engineering