Biomaterials with the ability to self-heal and recover their structural integrity offer many advantages for applications in biomedicine. The past decade has witnessed the rapid emergence of a new class of self-healing biomaterials commonly termed injectable, or printable in the context of 3D printing. These self-healing injectable biomaterials, mostly hydrogels and other soft condensed matter based on reversible chemistry, are able to temporarily fluidize under shear stress and subsequently recover their original mechanical properties. Self-healing injectable hydrogels offer distinct advantages compared to traditional biomaterials. Most notably, they can be administered in a locally targeted and minimally invasive manner through a narrow syringe without the need for invasive surgery. Their moldability allows for a patient-specific intervention and shows great prospects for personalized medicine. Injected hydrogels can facilitate tissue regeneration in multiple ways owing to their viscoelastic and diffusive nature, ranging from simple mechanical support, spatiotemporally controlled delivery of cells or therapeutics, to local recruitment and modulation of host cells to promote tissue regeneration. Consequently, self-healing injectable hydrogels have been at the forefront of many cutting-edge tissue regeneration strategies. This study provides a critical review of the current state of self-healing injectable hydrogels for tissue regeneration. As key challenges toward further maturation of this exciting research field, we identify (i) the trade-off between the self-healing and injectability of hydrogels vs their physical stability, (ii) the lack of consensus on rheological characterization and quantitative benchmarks for self-healing injectable hydrogels, particularly regarding the capillary flow in syringes, and (iii) practical limitations regarding translation toward therapeutically effective formulations for regeneration of specific tissues. Hence, here we (i) review chemical and physical design strategies for self-healing injectable hydrogels, (ii) provide a practical guide for their rheological analysis, and (iii) showcase their applicability for regeneration of various tissues and 3D printing of complex tissues and organoids.

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用于组织再生的自愈可注射水凝胶

具有自我修复和恢复结构完整性能力的生物材料为生物医学应用提供了许多优势。在过去的十年中，一类新的自修复生物材料迅速出现，通常在 3D 打印的背景下被称为可注射或可打印。这些可自我修复的可注射生物材料，主要是水凝胶和其他基于可逆化学的软凝聚物质，能够在剪切应力下暂时流化，随后恢复其原始机械性能。与传统生物材料相比，自愈可注射水凝胶具有明显的优势。最值得注意的是，它们可以通过狭窄的注射器以局部靶向和微创方式进行给药，而无需进行侵入性手术。它们的可塑性允许针对特定患者进行干预，并显示出个性化医疗的广阔前景。由于其粘弹性和扩散特性，注射的水凝胶可以通过多种方式促进组织再生，从简单的机械支持、时空控制的细胞或治疗剂递送，到宿主细胞的局部募集和调节以促进组织再生。因此，自我修复的可注射水凝胶一直处于许多尖端组织再生策略的前沿。本研究对用于组织再生的自修复可注射水凝胶的现状进行了批判性回顾。作为这一激动人心的研究领域进一步成熟的关键挑战，我们确定 (i) 水凝胶的自愈和可注射性与其物理稳定性之间的权衡，(ii) 在自愈可注射水凝胶的流变学表征和定量基准方面缺乏共识，特别是关于注射器中的毛细管流动，和（iii）关于转化为特定组织再生的治疗有效制剂的实际限制。因此，在这里，我们 (i) 回顾自修复可注射水凝胶的化学和物理设计策略，(ii) 为其流变学分析提供实用指南，以及 (iii) 展示它们在各种组织再生和复杂组织 3D 打印中的适用性和类器官。特别是关于注射器中的毛细管流动，以及（iii）关于转化为用于特定组织再生的治疗有效制剂的实际限制。因此，在这里，我们 (i) 回顾自修复可注射水凝胶的化学和物理设计策略，(ii) 为其流变学分析提供实用指南，以及 (iii) 展示它们在各种组织再生和复杂组织 3D 打印中的适用性和类器官。特别是关于注射器中的毛细管流动，以及（iii）关于转化为用于特定组织再生的治疗有效制剂的实际限制。因此，在这里，我们 (i) 回顾自修复可注射水凝胶的化学和物理设计策略，(ii) 为其流变学分析提供实用指南，以及 (iii) 展示它们在各种组织再生和复杂组织 3D 打印中的适用性和类器官。