title: Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs.
abstract: There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0-2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising 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.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
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; Department of Equine Sciences, Utrecht University, P.O. Box 80153, 3508 TD, Utrecht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Malda
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Klein
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D001696:Biomechanical Phenomena / Q000187:drug effects; D002356:Cartilage / Q000166:cytology* / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry; D055595:Mechanical Phenomena; D008689:Methacrylates / Q000737:chemistry; D023822:Tissue Engineering; D055114:X-Ray Microtomography
chemical_list: D000178:Acrylamides; D006025:Glycosaminoglycans; D020100:Hydrogels; D008689:Methacrylates; C008384:methacrylic acid; D005780:Gelatin; D006820:Hyaluronic Acid; C045985:methacrylamide