Endogenous dual-responsive and self-adaptive silk fibroin-based scaffold with enhancement of immunomodulation for skull regeneration

作者：Xuewei Bi, Zhinan Mao, Yilin Zhang, Zeqi Ren, Kang Yang, Chunhao Yu, Lei Chen, Rui Zheng, Juan Guan, Zhenhai Liu, Bin-Sheng Yu, Yong‐Can Huang, Xiong Shu, Yufeng Zheng · 发表于：Biomaterials · 年份：2025 · DOI：10.1016/j.biomaterials.2025.123261 · 被引用次数：27 · 研究领域：Silk-based biomaterials and applications、Corneal Surgery and Treatments、Bone Tissue Engineering Materials

Despite the current biomaterials (e.g. titanium mesh and polyether ether ketone) have been applied to clinical skull repair, the limitations on mechanical match, shape adaptability, bioactivity and osteointegration have greatly limited their clinical application. In this work, we constructed a water and inflammatory microenvironment dual-responsive self-adaptive silk fibroin-magnesium oxide-based scaffold with the matrix metalloproteinase-2-responsive gelatin-methacryloyl-interleukin-4 (IL-4) coating, which presented good mechanical compliance, quickly shape matching and intraoperative reprocessability. With the capability of responding to an acute inflammation microenvironment followed by a triggered on-demand release of the IL-4, the combination of immunoactive IL-4 and Mg 2+ co-ordinately facilitated metabolic reprogramming by suppressing glycolysis, promoting mitochondrial oxidative phosphorylation and modulating adenosine 5′-monophosphate-activated protein kinase (AMPK) signalling pathways in macrophages, resulting in significantly facilitating M2 macrophage activation . During the stage of tissue remodelling, the sustained release of Mg 2+ further promoted macrophage M2 polarization and the expression of anti-inflammatory cytokines, significantly reduced immune response and improved ectopic osteogenesis ability. Meanwhile, the cranial defect models of male rats demonstrated that this scaffold could significantly enhance biomineralized deposition and vascularisation , an...