Duan Qida, Shao Hongyun, Luo Ning, Wang Fuyang, Cheng Liangliang, Ying Jiawei, Zhao Dewei
Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Front Bioeng Biotechnol. 2025 Sep 4;13:1614727. doi: 10.3389/fbioe.2025.1614727. eCollection 2025.
With the advancements in tissue engineering, materials science, microsurgery, and the maturation of 3D printing technology, 3D-printed artificial bone scaffolds have provided an innovative strategy that integrates structural bionics and functional synergy for the treatment of large-segment bone defects. Compared with conventional bone grafting, this technology not only precisely reconstructs anatomical geometry and promotes cell migration through porous design, but also, via surface modification, enables accurate loading and controlled release of multiple bioactive factors, thereby actively regulating osteogenesis and angiogenesis, enhancing regeneration efficiency, and overcoming the traditional scaffold limitation of "mechanical support only, lack of biological guidance." Nevertheless, repair of large-segment defects still faces challenges such as early ischemia, restricted nutrient diffusion, and slow callus formation. To address this bottleneck, the present study summarizes a "vascularization-osteogenesis integration" scaffold design paradigm that combines 3D printing with vascularized bone substitutes, realizing a "scaffold plus vascular-pedicled flap" co-implantation strategy; the vascular network of the flap traverses the entire scaffold, establishing a co-culture microenvironment of endothelial cells and mesenchymal stem cells and maximizing osteogenic and angiogenic efficiency. This review systematically analyzes the biomaterial properties of various 3D-printed bone scaffolds, strategies for loading bioactive factors, and cutting-edge progress in pedicled flap transplantation for bone and vessel regeneration, highlighting their distinctive advantages in vascularization and bioactivity modulation over traditional bone grafting, aiming to promote a paradigm shift from "structural replacement" to "biological function reconstruction" and provide both theoretical innovation and practical guidance for accelerating clinical translation of bone tissue engineering.
随着组织工程、材料科学、显微外科的进步以及3D打印技术的成熟，3D打印人工骨支架为治疗大段骨缺损提供了一种融合结构仿生与功能协同的创新策略。与传统骨移植相比，该技术不仅通过多孔设计精确重建解剖几何结构并促进细胞迁移，还能通过表面修饰实现多种生物活性因子的精确加载和控释，从而积极调节成骨和血管生成，提高再生效率，克服了传统支架“仅提供机械支撑，缺乏生物引导”的局限性。然而，大段骨缺损的修复仍面临早期缺血、营养物质扩散受限以及骨痂形成缓慢等挑战。为解决这一瓶颈问题，本研究总结了一种“血管化-成骨一体化”支架设计模式，即将3D打印与带血管蒂骨替代物相结合，实现“支架加血管蒂皮瓣”联合植入策略；皮瓣的血管网络贯穿整个支架，建立内皮细胞与间充质干细胞的共培养微环境，最大化成骨和血管生成效率。本综述系统分析了各种3D打印骨支架的生物材料特性、生物活性因子加载策略以及带蒂皮瓣移植促进骨与血管再生的前沿进展，突出了它们在血管化和生物活性调节方面相对于传统骨移植的独特优势，旨在推动从“结构替代”到“生物功能重建”的模式转变，为加速骨组织工程的临床转化提供理论创新和实践指导。
