Zhou Bixia, Jiang Xulei, Zhou Xinxin, Tan Wuyuan, Luo Hang, Lei Shaorong, Yang Ying
Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, PR China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
Biomater Res. 2023 Sep 15;27(1):86. doi: 10.1186/s40824-023-00422-6.
Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these defects with synthetic bone substitutes is the most common strategy. In general, tissue engineering materials that mimic the structural, mechanical and biological properties of natural bone have been extensively applied to fill bone defects and promote in situ bone regeneration. Hydrogels with extracellular matrix (ECM)-like properties are common tissue engineering materials, among which methacrylate-based gelatin (GelMA) hydrogels are widely used because of their tunable mechanical properties, excellent photocrosslinking capability and good biocompatibility. Owing to their lack of osteogenic activity, however, GelMA hydrogels are combined with other types of materials with osteogenic activities to improve the osteogenic capability of the current composites. There are three main aspects to consider when enhancing the bone regenerative performance of composite materials: osteoconductivity, vascularization and osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors and two-dimensional (2D) nanomaterials have been applied in various combinations to achieve enhanced osteogenic and bone regeneration activities. Three-dimensional (3D)-bioprinted scaffolds are a popular research topic in bone tissue engineering (BTE), and printed and customized scaffolds are suitable for restoring large irregular bone defects due to their shape and structural tunability, enhanced mechanical properties, and good biocompatibility. Herein, the recent progress in research on GelMA-based composite hydrogel scaffolds as multifunctional platforms for restoring critical bone defects in plastic or orthopedic clinics is systematically reviewed and summarized. These strategies pave the way for the design of biomimetic bone substitutes for effective bone reconstruction with good biosafety. This review provides novel insights into the development and current trends of research on GelMA-based hydrogels as effective bone tissue engineering (BTE) scaffolds for correcting bone defects, and these contents are summarized and emphasized from various perspectives (osteoconductivity, vascularization, osteoinduction and 3D-bioprinting). In addition, advantages and deficiencies of GelMA-based bone substitutes used for bone regeneration are put forward, and corresponding improvement measures are presented prior to their clinical application in near future (created with BioRender.com).
目前，由各种原因导致的严重骨缺损的临床治疗仍然是一个巨大的挑战，使用合成骨替代物修复这些缺损是最常见的策略。一般来说，模仿天然骨结构、力学和生物学特性的组织工程材料已被广泛应用于填充骨缺损并促进原位骨再生。具有细胞外基质（ECM）样特性的水凝胶是常见的组织工程材料，其中基于甲基丙烯酸酯的明胶（GelMA）水凝胶因其可调的力学性能、优异的光交联能力和良好的生物相容性而被广泛使用。然而，由于缺乏成骨活性，GelMA水凝胶与其他具有成骨活性的材料结合，以提高当前复合材料的成骨能力。在提高复合材料的骨再生性能时，有三个主要方面需要考虑：骨传导性、血管化和骨诱导。生物陶瓷、生物玻璃、仿生支架、无机离子、仿生骨膜、生长因子和二维（2D）纳米材料已被以各种组合应用，以实现增强的成骨和骨再生活性。三维（3D）生物打印支架是骨组织工程（BTE）中一个热门的研究课题，打印和定制的支架由于其形状和结构的可调性、增强的力学性能和良好的生物相容性，适合于修复大型不规则骨缺损。在此，系统地综述和总结了基于GelMA的复合水凝胶支架作为修复整形或骨科临床严重骨缺损的多功能平台的研究进展。这些策略为设计具有良好生物安全性的仿生骨替代物以进行有效的骨重建铺平了道路。本综述为基于GelMA的水凝胶作为矫正骨缺损的有效骨组织工程（BTE）支架的开发和当前研究趋势提供了新的见解，并且从各个角度（骨传导性、血管化、骨诱导和3D生物打印）对这些内容进行了总结和强调。此外，还提出了用于骨再生的基于GelMA的骨替代物的优点和不足，并在不久的将来临床应用之前提出了相应的改进措施（由BioRender.com创建）。
