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用于组织再生的自修复可注射水凝胶。

Self-Healing Injectable Hydrogels for Tissue Regeneration.

机构信息

Department of Dentistry-Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 EX Nijmegen, The Netherlands.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.

出版信息

Chem Rev. 2023 Jan 25;123(2):834-873. doi: 10.1021/acs.chemrev.2c00179. Epub 2022 Aug 5.

Abstract

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.

摘要

具有自修复和恢复结构完整性能力的生物材料在生物医学应用中具有许多优势。在过去的十年中,一种新的自修复生物材料类别迅速出现,通常在 3D 打印的背景下称为可注射或可打印。这些自修复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态物质,能够在剪切应力下临时流体化,并随后恢复其原始机械性能。与传统生物材料相比,自修复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的方式给药,而无需进行侵入性手术。它们的可模塑性允许进行特定于患者的干预,并为个性化医疗提供了广阔的前景。由于其粘弹性和扩散性质,注入的水凝胶可以通过多种方式促进组织再生,从简单的机械支撑、时空控制细胞或治疗剂的递送,到局部募集和调节宿主细胞以促进组织再生。因此,自修复可注射水凝胶一直处于许多前沿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。作为该令人兴奋的研究领域进一步成熟的关键挑战,我们确定了 (i) 水凝胶的自修复和可注射性与其物理稳定性之间的权衡,(ii) 缺乏关于自修复可注射水凝胶的流变学特征和定量基准的共识,特别是关于注射器中的毛细流动,以及 (iii) 关于针对特定组织再生的治疗有效的制剂转化的实际限制。因此,在这里,我们 (i) 回顾了自修复可注射水凝胶的化学和物理设计策略,(ii) 提供了其实用的流变分析指南,以及 (iii) 展示了它们在各种组织再生和复杂组织和类器官的 3D 打印中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4510/9881015/1bf3674b703f/cr2c00179_0001.jpg

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