Silk Hydrogels as Soft Substrates for Neural Tissue Engineering

• Published in: Advanced functional materials Vol. 23; no. 41; pp. 5140 - 5149
• Main Authors: Hopkins, Amy M., De Laporte, Laura, Tortelli, Federico, Spedden, Elise, Staii, Cristian, Atherton, Timothy J., Hubbell, Jeffrey A., Kaplan, David L.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 06.11.2013; WILEY‐VCH Verlag
• Subjects: biomedical applications; biomimetics; extracellular matrix engineering; hydrogels; tissue engineering
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201300435

There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8% silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4% silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5% of neurotrophin‐3 (NT‐3) over 2 weeks and 11‐day old gels show maintenance of growth factor bioactivity. Finally, fibronectin‐ and NT‐3‐functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering. Silk hydrogels are soft biomaterials of stiffness matching that of nervous system tissues. Significant chick dorsal root ganglion explant outgrowth is exhibited on 2 to 4% w/v silk hydrogels supplemented with neurotrophic factors exemplifying their employment in extracellular matrix functionalization for neural tissue engineering applications.