透明质酸水凝胶材料在类器官领域的应用进展

Application Progress of Hyaluronic Acid Hydrogel Materials in Organoid Field

摘要: 类器官作为体外构建的三维微型组织模型，在器官发育研究、疾病建模及药物筛选中展现出重要价值，其构建高度依赖仿生培养基质。传统动物源基质材料因成分不明确、批次差异大及理化性能难以调控，限制了类器官体系的可重复性与工程化应用。透明质酸作为天然细胞外基质的重要组成成分，具有优异的生物相容性、可修饰性及力学可调性，为构建定义化、可控的类器官培养体系提供了新思路。近年来，基于物理、化学及生物交联策略构建的透明质酸水凝胶，已被广泛应用于肿瘤、肠道、肝脏、神经及组织修复相关的类器官模型中。相关研究表明，该类水凝胶不仅能够支持类器官的自组织、生长稳定性及功能成熟，还可作为活性基质信号分子，通过与细胞表面受体相互作用参与炎症调节、干细胞维持及血管生成等关键生物过程。本文系统综述了透明质酸水凝胶的制备方法及材料特性，重点总结其在不同类器官培养体系中的应用进展，并讨论其在微环境调控、标准化构建及工程化应用方面面临的挑战与未来发展方向，为构建高仿生、可重复且具有转化潜力的类器官培养体系提供参考。

Abstract: As three-dimensional microtissue models constructed in vitro, organoids demonstrate significant value in organ development research, disease modeling, and drug screening, with their construction highly dependent on biomimetic culture matrices. Traditional animal-derived matrix materials, due to unclear composition, significant batch variations, and difficulties in regulating physicochemical properties, have limited the reproducibility and engineering applications of organoid systems. Hyaluronic acid (HA), as a crucial component of natural extracellular matrices, exhibits excellent biocompatibility, modifiability, and mechanical tunability, providing novel insights for constructing defined and controllable organoid culture systems. In recent years, HA hydrogels fabricated through physical, chemical, and biological crosslinking strategies have been widely applied in tumor, intestinal, hepatic, neural, and tissue repair-related organoid models. Relevant studies indicate that this type of hydrogel not only supports the self-organization, growth stability, and functional maturation of organoids, but also serves as an active matrix signaling molecule. Through interactions with cell surface receptors, it participates in critical biological processes such as inflammation regulation, stem cell maintenance, and angiogenesis. This article systematically reviews the preparation methods and material properties of HA hydrogels, focuses on summarizing their application progress in various organoid cultures, and outlines key challenges and future directions, offering references for developing highly biomimetic, reproducible, and translational potential organoid culture systems.