A temporally functional composite hydrogel scaffold for cranial defect repair via sequential modulation of angiogenesis and osteogenesis

作者：Zeen Lv, Bo Sun, Li Rong, Bowen Zhao, Hongxiang Wang, Ning Luo, Xin Ding, Xuan Tang, Chunlin Wang, Long Bai, Jiacan Su, Juxiang Chen · 发表于：Theranostics · 年份：2025 · DOI：10.7150/thno.119835 · 被引用次数：3 · 研究领域：Silk-based biomaterials and applications、Bone Tissue Engineering Materials、Head and Neck Surgical Oncology

The repair of large cranial defects remains a major clinical challenge, as conventional materials primarily act as inert fillers and fail to meet the complex biological requirements of cranial bone regeneration.In particular, they lack the ability to temporally coordinate angiogenesis and osteogenesis.This study aimed to develop a temporally functional composite scaffold to dynamically modulate the regenerative microenvironment and promote sequential vascularized bone regeneration.Methods: A silk fibroin-based hydrogel system was designed, incorporating salvianolic acid B (SalB)-loaded sustained-release hydrogel and mineralized silk fibroin hydrogel microspheres (MSFM).Material characterization was performed to evaluate the structural and mechanical properties of the scaffold, as well as the drug release behavior.In vitro assays were conducted to assess endothelial cell migration, tube formation, and the expression of angiogenesis-related genes, along with the osteogenic differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs).In vivo reparative efficacy was further validated using a rat cranial defect model through morphological and histological analyses.Results: Characterization confirmed that OSFM microgels were uniformly spherical with a porous internal structure and exhibited sustained release of OGP.In vitro, OSFM showed excellent cytocompatibility with BMSCs, significantly enhancing cell proliferation, ALP activity, and mineralized nodule formati...