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Semi-interpenetrating networks of hyaluronic acid in degradable PEG hydrogels for cartilage tissue engineering
Institution:1. Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA;2. BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA;3. Materials Science and Engineering Program, University of Colorado, Boulder, CO 80309, USA;1. Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia;2. Department of Orthopaedics, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands;1. Department of Biomedical Engineering, Duke University, Durham, NC, USA;2. Department of Chemistry, Duke University, Durham, NC, USA;3. Department of Orthopaedic Surgery, Duke University, Durham, NC, USA;1. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, Queensland 4072, Australia;2. Mesoblast Ltd, Level 39, 55 Collins Street, Melbourne 3000, Australia;3. School of Biomedical Sciences, University of Queensland, St Lucia, Queensland 4072, Australia;4. Mesenchymal Stem Cell Laboratory, School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Adelaide, 5005 South Australia, Australia;5. Myeloma Research Laboratory, School of Medical Sciences, Faculty of Health Science, University of Adelaide, Centre for Stem Cell Research, Robinson Institute, University of Adelaide, Adelaide, South Australia 5000, Australia;6. School of Chemical Engineering, University of Queensland, St. Lucia, Queensland 4072, Australia;1. Bioengineering Department, University of California Los Angeles, Los Angeles, CA 90095, USA;2. Chemical and Biomolecular Engineering Department, University of California Los Angeles, Los Angeles, CA 90095, USA
Abstract:Hydrolytically biodegradable poly(ethylene glycol) (PEG) hydrogels offer a promising platform for chondrocyte encapsulation and tuning degradation for cartilage tissue engineering, but offer no bioactive cues to encapsulated cells. This study tests the hypothesis that a semi-interpenetrating network of entrapped hyaluronic acid (HA), a bioactive molecule that binds cell surface receptors on chondrocytes, and crosslinked degradable PEG improves matrix synthesis by encapsulated chondrocytes. Degradation was achieved by incorporating oligo (lactic acid) segments into the crosslinks. The effects of HA molecular weight (MW) (2.9 × 104 and 2 × 106 Da) and concentration (0.5 and 5 mg g?1) were investigated. Bovine chondrocytes were encapsulated in semi-interpenetrating networks and cultured for 4 weeks. A steady release of HA was observed over the course of the study with 90% released by 4 weeks. Incorporation of HA led to significantly higher cell numbers throughout the culture period. After 8 days, HA increased collagen content per cell, increased aggrecan-positive cells, while decreasing the deposition of hypertrophic collagen X, but these effects were not sustained long term. Measuring total sulfated glycosaminoglycan (sGAG) and collagen content within the constructs and released to the culture medium after 4 weeks revealed that total matrix synthesis was elevated by high concentrations of HA, indicating that HA stimulated matrix production although this matrix was not retained within the hydrogels. Matrix-degrading enzymes were elevated in the low-, but not the high-MW HA. Overall, incorporating high-MW HA into degrading hydrogels increased chondrocyte number and sGAG and collagen production, warranting further investigations to improve retention of newly synthesized matrix molecules.
Keywords:Hyaluronic acid  Poly(ethylene glycol) hydrogel  Degradable biomaterials  Cartilage tissue engineering
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