journal article·2025-09-16

Directional Biomimetic Scaffold-Mediated Cell Migration and Pathological Microenvironment Regulation Accelerate Diabetic Bone Defect Repair

Bingbing Wang, Shengzhao Xiao, Jie Liao, Yong Huang, Xiali Guan, Cunyang Wang, Chao Xue, Qiang Cai, Xiaoming Li

ACS Nano· Volume 19· Issue 36
Publisher page

Abstract

Hyperglycemia-induced oxidative stress and inflammation critically impair diabetic bone defect repair. Here, a radially oriented microchannel scaffold (D-GSH@QZ) was developed via a directional freezing technique integrated with photo-cross-linking strategies. The scaffold was fabricated from gelatin methacryloyl, silk fibroin methacryloyl, and nanohydroxyapatite (HAp) to mimic the natural bone matrix, while incorporating quercetin-loaded ZIF-8 nanoparticles (Qu@ZIF-8) for pathological microenvironment modulation. By leveraging the advantages of directionally aligned structures and functional components (Qu@ZIF-8 and HAp), the scaffold facilitated rapid cell infiltration and guided orderly tissue regeneration from the periphery to the interior. Moreover, the scaffold induced macrophage M2 polarization, scavenged excess reactive oxygen species, and restored mitochondrial membrane potential, thereby remodeling the diabetic pathological microenvironment to enhance vascularization and osteogenesis. After implantation in the diabetic bone defect model, the scaffold significantly accelerated tissue repair. Furthermore, transcriptome sequencing of the regenerated tissue in vivo revealed that the scaffold inhibited pathways associated with oxidative stress, inflammation, and bone resorption, including AGE-RAGE, NF-κB, and osteoclast differentiation, while simultaneously activating key pathways related to angiogenesis and bone regeneration, such as TGF-β, PI3K-AKT, and Wnt pathways. These findings indicate that the D-GSH@QZ scaffold can provide an optimal 3D microenvironment for diabetic bone repair.
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Research context

OpenAlex topics: Cellular Mechanics and Interactions · 3D Printing in Biomedical Research · Bone Tissue Engineering Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices of Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering

Beihang University

Department of Orthodontics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology

Shanghai Jiao Tong University

Department of Biomedical Materials Science, College of Biomedical Engineering

Third Military Medical University

College of Lab Medicine, Key Laboratory of Biomedical Materials of Zhangjiakou

Hebei North University

Key Laboratory of Advanced Materials of Ministry of Education

Tsinghua University

Senior Department of Orthopedics

the Fourth Medical Center of PLA General Hospital

Funding

Shanghai Jiao Tong University · Natural Science Foundation of Hebei Province · Fok Ying Tung Education Foundation · National Natural Science Foundation of China · the International Joint Research Center of Aerospace Biotechnology and Medical Engineering, Ministry of Science and Technology of China, and the 111 Project · International Joint Research Center of Aerospace Biotechnology and Medical Engineering, Ministry of Science and Technology of China, and the 111 Project · Beijing Nova Programme Interdisciplinary Cooperation Project · Beijing Natural Science Foundation

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