Tough Porous Silk Nanofiber‐Derived Cryogels with Osteogenic and Angiogenic Capacity for Bone Repair

Abstract

Tough porous cryogels with angiogenesis and osteogenesis features remain a design challenge for utility in bone regeneration. Here, building off of the recent efforts to generate tough silk nanofiber‐derived cryogels with osteogenic activity, deferoxamine (DFO) is loaded in silk nanofiber‐derived cryogels to introduce angiogenic capacity. Both the mechanical cues (stiffness) and the sustained release of DFO from the gels are controlled by tuning the concentration of silk nanofibers in the system, achieving a modulus above 400 kPa and slow release of the DFO over 60 days. The modulus of the cryogels and the released DFO induce osteogenic and angiogenic activity, which facilitates bone regeneration in vivo in femur defects in rat, resulting in faster regeneration of vascularized bone tissue. The tunable physical and chemical cues derived from these nanofibrous‐microporous structures support the potential for silk cryogels in bone tissue regeneration.

Simulation of Cortical and Cancellous Bone to Accelerate Tissue Regeneration

“…[ 29 ] Higher stiffness usually implies stronger mechanical cues to induce osteogenic behaviors. [ 16,29,43 ] Thus, the osteogenic capacity of the cryogels was improved following the increase in stiffness. When BMSCs were cultured in the cryogels with different porous structures and stiffness for 14 and 28 days, the highest osteodifferentiation was achieved for the cells in the SNFH‐A cryogel with the highest modulus, while the cells in the SNFH‐H cryogel with the lowest stiffness showed the weakest osteodifferentiation (Figure 2d,f,g).…”

“…[29,[41][42][43] In the crosslinking reaction, the phenyl hydroxyl group was reacted to crosslink various silk fibroins, inducing cryogel formation. [29,[41][42][43] Since the ASNFs had richer phenyl group on the nanofiber surface, the cryogels with higher crosslinking density were prepared and achieved significant higher mechanical properties than that prepared with traditional silk fibroin soluiton under same crosslinking conditions. [29,43] The tough ASNF cryogels had suitable stiffness to induce osteodifferentiation and were used to form homogeneous porous scaffolds in our present study.…”

“…[29,[41][42][43] Since the ASNFs had richer phenyl group on the nanofiber surface, the cryogels with higher crosslinking density were prepared and achieved significant higher mechanical properties than that prepared with traditional silk fibroin soluiton under same crosslinking conditions. [29,43] The tough ASNF cryogels had suitable stiffness to induce osteodifferentiation and were used to form homogeneous porous scaffolds in our present study. As shown in Scheme 1, when the blended solutions were treated with the electrical field and EGDE simultaneously, the BSNFs migrated toward the positive electrode and assembled to annular lamellar hydrogels while the ASNFs remained stationary and were gradually crosslinked through EGDE.…”

Silk Nanofiber Scaffolds with Multiple Angiogenic Cues to Accelerate Wound Regeneration

“…Therefore, long-term angiogenic capacity could be anticipated through the slow release of DFO. Compared to the RSS–DFO scaffolds, a lower release rate of DFO occurred in the ASS–DFO scaffolds, likely due to the aligned compact BSNF layers in the scaffolds that further slowed the DFO release . The compact aligned layers inside the scaffolds affected the degradation behavior.…”

“…The cytotoxicity of DFO was alleviated when loaded on BSNFs (Figure ). Previous studies revealed that 120 μM of DFO loaded on BSNFs induced effective angiogenesis without cytotoxicity. , BMSCs were cultured on different composite scaffolds to evaluate the influence of the loaded DFO on cytocompatibility. Similar to that on DFO-loaded BSNF hydrogels, BMSCs proliferated steadily without reaching a plateau until 12 days on all of the composite scaffolds.…”