Semeraro Francesca, Herrera Millar Valentina Rafaela, Aidos Lucia, Sergio Mirko, Impieri Lorenzo, Peretti Giuseppe Michele, Mangiavini Laura, Di Giancamillo Alessia, Rossi Nicolò
Residency Program in Orthopedics and Traumatology, University of Milan, 20141 Milan, Italy.
Department of Biomedical Sciences for Health, University of Milan, 20141 Milan, Italy.
Gels. 2025 Aug 19;11(8):658. doi: 10.3390/gels11080658.
Osteochondral regeneration remains a major clinical challenge due to the complex architecture and biomechanical demands of the osteochondral unit. Bioactive hydrogels have emerged as promising materials capable of supporting repair through their capacity to mimic the extracellular matrix (ECM), enable cell encapsulation, and deliver bioactive cues. However, recent insights reveal that simply engineering hydrogels for structural and cellular support is insufficient. A new paradigm is emerging-one that embraces the complexity of the osteochondral niche by integrating immunomodulatory and mechanobiological cues into biomaterial design. In particular, the hydrogel's capacity to modulate macrophage polarization and support the immunoregulatory function of mesenchymal stem cells (MSCs) is critical to orchestrate regenerative outcomes. Simultaneously, the mechanical properties of hydrogels-such as stiffness, porosity, and viscoelasticity-can profoundly influence stem cell fate and local tissue morphogenesis. This review discusses recent advances in hydrogel-based strategies for osteochondral repair, highlighting the interplay between immunological signals and the mechanical microenvironment, and calls for a shift from reductionist tissue-engineering approaches to systems-level design of tunable, immuno-mechanobiological microenvironments.
由于骨软骨单元复杂的结构和生物力学要求，骨软骨再生仍然是一项重大的临床挑战。生物活性水凝胶已成为有前景的材料，它们能够通过模拟细胞外基质（ECM）、实现细胞封装以及传递生物活性信号来支持修复。然而，最近的研究表明，仅仅设计用于结构和细胞支持的水凝胶是不够的。一种新的范例正在出现，即通过将免疫调节和力学生物学信号整合到生物材料设计中，来涵盖骨软骨微环境的复杂性。特别是，水凝胶调节巨噬细胞极化和支持间充质干细胞（MSC）免疫调节功能的能力对于协调再生结果至关重要。同时，水凝胶的机械性能，如硬度、孔隙率和粘弹性，可深刻影响干细胞命运和局部组织形态发生。本文综述了基于水凝胶的骨软骨修复策略的最新进展，强调了免疫信号与机械微环境之间的相互作用，并呼吁从简化的组织工程方法转向可调谐的免疫 - 力学生物学微环境的系统级设计。
