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Successful repair of long-distance peripheral nerve injuries remains a challenge in the clinic. Rapid axon growth is a key to accelerate nerve regeneration. Herein, a pure silk fibroin (SF) hydrogel with a combination of high-strength and aligned microgrooved topographic structure is reported. The hydrogels exhibit excellent mechanical properties with high strength. Good biocompatibility also allows the hydrogels to support cell survival. Significantly, the hydrogel with aligned microgrooved structures enables the aligned growth of Schwann cells. Moreover, the hydrogel holds a strong capacity for promoting axon growth and guiding neurite sprouting. Thus, this micropatterned SF hydrogel would have great potential for peripheral nerve regeneration.

Due to the complex spatial‐temporal pathophysiology of spinal cord injury (SCI), effective modulation of SCI‐specific inflammatory pathogenesis to achieve desirable therapeutic effects on functional recovery still remains challenging. Herein, cell‐enhanced photocrosslinked silk fibroin hydrogels with extracellular matrix‐mimicking cues of mechanical properties and RGD (Arg‐Gly‐Asp) signals are gelled in situ to fill the lesion site to modulate injury‐induced neuroinflammation and promote neurite regrowth after SCI. The bionic hydrogel system provides biomimetic mechanical cues to promote neuronal differentiation of neural stem/progenitor cells (NPCs) and neurite growth by activating YAP nuclear expression. Importantly, favored by the strong capacity of silk fibroin hydrogels on macrophage/microglia recruitment, NPCs encapsulated hydrogel (NPCs@SFRGD0.1) effectively promotes recruited macrophages/microglia to M2 polarization in the lesion site by releasing S100A4 and thereby remodels the inflammatory microenvironment after SCI. Moreover, NPCs@SFRGD0.1 successfully reduces glial scar formation and accelerates corticospinal tract axon regrowth to improve locomotor recovery. Overall, this work contributes to illustrating the therapeutic mechanism of NPCs development based biomaterial therapies on modulating inflammatory microenvironment and this NPCs enhanced silk fibroin hydrogel provides a promising therapeutic strategy for SCI. [ABSTRACT FROM AUTHOR]

Easy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk‐inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned "on" via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light‐controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk‐based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration. [ABSTRACT FROM AUTHOR]