Laminin-111 functionalized polyethylene glycol hydrogels support myogenic activity in vitro

• Published in: Biomedical materials (Bristol) 2018-08, Vol.13 (6), p.065007-065007
• Main Authors: Ziemkiewicz, Natalia, Talovic, Muhamed, Madsen, Josh, Hill, Lindsay, Scheidt, Robert, Patel, Anjali, Haas, Gabriel, Marcinczyk, Madison, Zustiak, Silviya P, Garg, Koyal
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biocompatible Materials; Cell Adhesion; Cell Proliferation; Cell Survival; Elasticity; Hydrogels - chemistry; In Vitro Techniques; Interleukin-6 - metabolism; Laminin - chemistry; laminin-111; Mice; Muscle Development; Muscle, Skeletal - drug effects; Muscle, Skeletal - injuries; Myoblasts - metabolism; myogenesis; Myogenin - metabolism; poly(ethylene glycol); Polyethylene Glycols - chemistry; Regeneration; Rheology; Stress, Mechanical; Viscosity; Wound Healing - drug effects
• ISSN: 1748-605X; 1748-605X
• DOI: 10.1088/1748-605X/aad915

Skeletal muscle has a remarkable regenerative capability following mild physical or chemical insult. However, following a critical loss of muscle tissue, the regeneration process is impaired due to the inadequate myogenic activity of muscle resident stem cells (i.e., satellite cells). Laminin (LM) is a heterotrimeric structural protein in the satellite cell niche that is crucial for maintaining its function. In this study, we created hydrogels composed of poly (ethylene glycol) (PEG) and LM-111 to provide an elastic substrate for satellite cell proliferation at the site of injury. The PEG-LM111 conjugates were mixed with 5% and 10% (w/v) pure PEG-diacrylate (PEGDA) and photopolymerized to form 5% and 10% PEGLM gels. Pure 5% and 10% PEGDA gels were used as controls. The modulus of both hydrogels containing 10% (w/v) PEGDA was significantly higher than the hydrogels containing 5% (w/v) PEGDA. The 5% PEGLM hydrogels showed significantly higher swelling in aqueous medium suggesting a more porous structure. C2C12 myoblasts cultured on the softer 5% PEGLM hydrogels showed a flat and spread-out morphology when compared to the rounded, multicell clusters formed on the 5% PEGDA, 10% PEGDA, and 10% PEGLM hydrogels. The 5% PEGLM hydrogels also promoted a significant increase in both vascular endothelial growth factor and interleukin-6 (IL-6) production from the myoblasts. Additionally, the expression of MyoD was significantly higher while that of myogenin and -actinin trended higher on the 5% PEGLM hydrogels compared to 5% PEGDA on day 5. Our data suggests that the introduction of LM-111 into compliant PEG hydrogels promoted myoblast adhesion, survival, pro-regenerative growth factor production, and myogenic activity.