Affiliation: | 1. Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, 215000 P. R. China;2. State Key Laboratory of Radiation Medicine and Radiation Protection, Institutes for Translational Medicine, Soochow University, Suzhou, 215123 P. R. China National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123 P. R. China;3. State Key Laboratory of Radiation Medicine and Radiation Protection, Institutes for Translational Medicine, Soochow University, Suzhou, 215123 P. R. China;4. Department of Biomedical Engineering, Tufts University, Medford, MA, 02155 USA |
Abstract: | Different tissues have complex anisotropic structures to support biological functions. Mimicking these complex structures in vitro remains a challenge in biomaterials designs. Here, inspired by different types of silk nanofibers, a composite materials strategy is pursued toward this challenge. A combination of fabrication methods is utilized to achieve separate control of amorphous and beta-sheet rich silk nanofibers in the same solution. Aqueous solutions containing two types of silk nanofibers are simultaneously treated with an electric field and with ethylene glycol diglycidyl ether (EGDE). Under these conditions, the beta-sheet rich silk nanofibers in the mixture responded to the electric field while the amorphous nanofibers are active in the crosslinking process with the EGDE. As a result, cryogels with anisotropic structures are prepared, including mimics for cortical- and cancellous-like bone biomaterials as a complex osteoinductive niche. In vitro studies revealed that mechanical cues of the cryogels induced osteodifferentiation of stem cells while the anisotropy inside the cryogels influenced immune reactions of macrophages. These bioactive cryogels also stimulated improved bone regeneration in vivo through modulation of inflammation, angiogenesis and osteogenesis responses, suggesting an effective strategy to develop bioactive matrices with complex anisotropic structures beneficial to tissue regeneration. |