Multifunctional NGF-loaded PLGA microsphere-PCL/GelMA scaffold enables coordinated osteo-neuro-vascular regeneration via PI3K/AKT pathway activation

作者：Shuai Tang, Jinyi Huang, Shu‐Shan Du, Wenyu Feng, Xiaolan Wang, Cheng Chen, Tong Yang, Gang Ding · 发表于：Chemical Engineering Journal · 年份：2025 · DOI：10.1016/j.cej.2025.165993 · 被引用次数：5 · 研究领域：Bone Tissue Engineering Materials、Mesenchymal stem cell research、Graphene and Nanomaterials Applications

Large bone defects, particularly in craniofacial regions, remain a major clinical challenge in orthopaedics and oral and maxillofacial surgery due to limited donor availability, immune rejection, and poor healing associated with conventional grafts. To address this problem, we developed a multifunctional composite scaffold by incorporating nerve growth factor (NGF)-loaded PLGA microspheres into a PCL/GelMA matrix, aiming for sustained NGF release and coordinated osteogenesis, angiogenesis, and neurogenesis. In vitro experiments demonstrated that the NGF-loaded scaffold significantly promoted osteogenic differentiation of dental pulp stem cells, as evidenced by increased alkaline phosphatase activity, mineralized nodule formation, and upregulated expression of RUNX2 , ALPL , COL1A1 , and BGLAP . In a rat critical-sized cranial defect model, the NGF-loaded scaffold promoted robust new bone formation, with increased bone volume fraction, trabecular thickness, and trabecular number compared to controls. Simultaneously, the NGF-loaded scaffold up-regulated the expression of vascular markers, including CD31 and α-SMA, and neural marker NF200, thus establishing a neurovascular-osteogenic regenerative microenvironment. Transcriptomic and western blot analysis further revealed activation of the PI3K/AKT pathway, upregulation of osteogenic transcription factors, such as Smad1/5 and Runx2 , and downregulation of osteoclast-associated genes. In contrast, scaffolds treated with the NGF pa...