Customizable Silk Fibroin-Based Hydrogel Fibrous Scaffold for On-Demand Multifaceted Tissue Repair

Hydrogel scaffolds represent an attractive tool for tissue repair. However, targeted tissue repair requires a specific shape and biological function design, and most natural-protein-based hydrogel scaffolds are predominantly confined to specific tissue repair applications. Here, we developed a versatile structural biomimetic natural protein platform through synergistic electrospinning, photopolymerization, and metal-coordination strategies. By integrating methacrylated silk fibroin (SFMA) with acrylated bisphosphonates (AcBP), we developed a dynamically functionalizable matrix that enables (1) customizable shape control via tunable electrospinning collectors and (2) on-demand biological function customization through metal-ion chelation. As a proof of concept, we demonstrate this platform’s scenario-specific therapeutic efficacy: (i) Mg²⁺-functionalized membranes (S-LB-Mg) that orchestrate angiogenic-osteogenic coupling in critical-sized calvarial defects, (ii) Ag⁺-integrated dressing (S-LB-Ag) enabling bacterial eradication via a nonantibiotic mechanism and accelerating infected wound closure, and (iii) Zn²⁺-loaded conduits (S-LB-Zn) that drive macrophage M2 polarization to enhance peripheral nerve regeneration. This naturally derived protein-based platform overcomes the potential side effects associated with clinical bioactive factor/antibiotic composite scaffolds, offering a simple and customizable solution for the repair and regeneration of diverse tissues in a cost-effective yet highly effective manner. Overall, our strategy provides an alternative perspective for constructing protein-derived hydrogel microfibers with customizable functions and shapes for tissue repair applications.