Simulation of Cortical and Cancellous Bone to Accelerate Tissue Regeneration

摘要

Different tissues have complex anisotropic structures to support biologicalfunctions. Mimicking these complex structures in vitro remains a challengein biomaterials designs. Here, inspired by different types of silk nanofibers,a composite materials strategy is pursued toward this challenge. A combinationof fabrication methods is utilized to achieve separate control of amorphousand beta-sheet rich silk nanofibers in the same solution. Aqueoussolutions containing two types of silk nanofibers are simultaneously treatedwith an electric field and with ethylene glycol diglycidyl ether (EGDE).Under these conditions, the beta-sheet rich silk nanofibers in the mixtureresponded to the electric field while the amorphous nanofibers are active inthe crosslinking process with the EGDE. As a result, cryogels with anisotropicstructures are prepared, including mimics for cortical- and cancellouslikebone biomaterials as a complex osteoinductive niche. In vitro studiesrevealed that mechanical cues of the cryogels induced osteodifferentiation ofstem cells while the anisotropy inside the cryogels influenced immune reactionsof macrophages. These bioactive cryogels also stimulated improvedbone regeneration in vivo through modulation of inflammation, angiogenesisand osteogenesis responses, suggesting an effective strategy to developbioactive matrices with complex anisotropic structures beneficial to tissueregeneration.