Huang Peiling, Wang Li, Heng Boon Chin, Haririan Ismaeil, Cai Qing, Ge Zigang
Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, 100871, China.
Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing 100081, PR China.
Acta Biomater. 2025 Jul 1;201:75-100. doi: 10.1016/j.actbio.2025.06.014. Epub 2025 Jun 7.
Hyaluronic acid (HA) as well as HA-based materials are widely applied in regenerative medicine due to their good biocompatibility, bioactivity and amenability to chemical modifications. Although the reactive sites and associated reaction types of HA have been summarized previously to guide chemical modification and synthesis of HA-based materials, the relationship between chemical modifications and HA-based material properties has not yet been discussed. In this review, the key properties of HA-based materials required for regenerative medicine in various tissues and organs including skin, bone, cartilage, heart and cornea are summarized and various chemical modification strategies aimed at achieving these properties are discussed. Versatile HA-based materials can be tailored through crosslinking and conjugation, as well as regulating the internal bonding types and degrees of modification. We also provide a comparative analysis of commonly used HA-based materials modification methods and discuss their practical advantages, limitations, and the current status of clinical translation. Even with significant progress already achieved, there is still a long way to go in precisely fine-tuning chemical modifications, balancing functionality and practicality, as well as in understanding their interactions with the diverse array of cells and tissues in vivo. This review bridges tissue-specific property demands with chemical design strategies. We believe that this demand-driven framework provides a practical and accessible guide for researchers intending to design HA-based materials with targeted regenerative capabilities. STATEMENT OF SIGNIFICANCE: This review critically examines hyaluronic acid (HA) and HA-based materials in regenerative medicine applications, focusing on the key properties required for applications in specific tissues such as skin, bone, cartilage, heart, and cornea, as well as the associated chemical modification strategies. While design strategies for HA-based materials have been studied in the past, the relationship between chemical modifications and the resulting material properties remains under-explored. This review thus addresses this gap by systematically categorizing various chemical modification strategies that have been tailored to different material property requirements, providing a comparative analysis of commonly used chemical modification methods, and discussing current clinical challenges and future directions of HA-based materials. By linking material properties to chemical modification strategies, this review thus provides a comprehensive guide for researchers and offers valuable insights for advancing the applications of HA-based materials in regenerative medicine.
透明质酸（HA）以及基于HA的材料因其良好的生物相容性、生物活性和化学修饰适应性，而被广泛应用于再生医学领域。尽管此前已经总结了HA的反应位点及相关反应类型，以指导基于HA的材料的化学修饰和合成，但尚未讨论化学修饰与基于HA的材料性能之间的关系。在本综述中，总结了包括皮肤、骨骼、软骨、心脏和角膜在内的各种组织和器官再生医学所需的基于HA的材料的关键特性，并讨论了旨在实现这些特性的各种化学修饰策略。通用的基于HA的材料可以通过交联和共轭，以及调节内部键合类型和修饰程度来定制。我们还对常用的基于HA的材料修饰方法进行了比较分析，并讨论了它们的实际优势、局限性以及临床转化的现状。即使已经取得了显著进展，但在精确微调化学修饰、平衡功能性和实用性，以及理解它们与体内各种细胞和组织的相互作用方面，仍有很长的路要走。本综述将组织特异性性能需求与化学设计策略联系起来。我们相信，这种需求驱动的框架为有意设计具有靶向再生能力的基于HA的材料的研究人员提供了实用且易懂的指南。重要性声明：本综述批判性地审视了再生医学应用中的透明质酸（HA）和基于HA的材料，重点关注在皮肤、骨骼、软骨、心脏和角膜等特定组织应用所需的关键特性，以及相关的化学修饰策略。虽然过去已经研究了基于HA的材料的设计策略，但化学修饰与所得材料性能之间的关系仍未得到充分探索。因此，本综述通过系统地分类针对不同材料性能要求定制的各种化学修饰策略、对常用化学修饰方法进行比较分析，以及讨论基于HA的材料当前的临床挑战和未来方向，填补了这一空白。通过将材料性能与化学修饰策略联系起来，本综述为研究人员提供了全面的指南，并为推进基于HA的材料在再生医学中的应用提供了有价值的见解。
