Walsh Ciara M, Wychowaniec Jacek K, Brougham Dermot F, Dooley Dearbhaile
School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland; UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland; AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.
Pharmacol Ther. 2022 Jun;234:108043. doi: 10.1016/j.pharmthera.2021.108043. Epub 2021 Nov 20.
Spinal cord injury (SCI) is a complex medical and psychological challenge for which there is no curative therapy currently available. Despite major progress in pharmacological and surgical approaches, clinical trials for SCI patients have been uniformly disappointing thus far as there are many practical and biological issues yet to be resolved. Neuroinflammation is a critical event of the secondary injury phase after SCI, and recent research strategies have focused on modulating the immune response after injury to provide a more favorable recovery environment. Biomaterials can serve this purpose by providing physical and trophic support to the injured spinal cord after SCI. Of all potential biomaterials, functional hydrogels are emerging as a key component in novel treatment strategies for SCI, including controlled and localized delivery of immunomodulatory therapies to drive polarization of immune cells towards a pro-regenerative phenotype. Here, we extensively review recent developments in the use of functional hydrogels as immunomodulatory therapies for SCI. We briefly describe physicochemical properties of hydrogels and demonstrate how advanced fabrication methods lead to the required heterogeneity and hierarchical arrangements that increasingly mimic complex spinal cord tissue. We then summarize potential SCI therapeutic modalities including: (i) hydrogels alone; (ii) hydrogels as cellular or (iii) bioactive molecule delivery vehicles, and; (iv) combinatorial approaches. By linking the structural properties of hydrogels to their functions in treatment with particular focus on immunopharmacological stimuli, this may accelerate further development of functional hydrogels for SCI, and indeed next-generation central nervous system regenerative therapies.
脊髓损伤（SCI）是一项复杂的医学和心理挑战，目前尚无治愈性疗法。尽管在药物和手术方法上取得了重大进展，但迄今为止，针对SCI患者的临床试验一直令人失望，因为仍有许多实际和生物学问题有待解决。神经炎症是SCI后继发性损伤阶段的关键事件，最近的研究策略集中在调节损伤后的免疫反应，以提供更有利的恢复环境。生物材料可以通过在SCI后为受损脊髓提供物理和营养支持来实现这一目的。在所有潜在的生物材料中，功能性水凝胶正在成为SCI新型治疗策略的关键组成部分，包括免疫调节疗法的可控和局部递送，以促使免疫细胞向促再生表型极化。在此，我们广泛综述了功能性水凝胶作为SCI免疫调节疗法的最新进展。我们简要描述了水凝胶的物理化学性质，并展示了先进的制造方法如何导致所需的异质性和层次排列，越来越多地模拟复杂的脊髓组织。然后，我们总结了潜在的SCI治疗方式，包括：（i）单独使用水凝胶；（ii）水凝胶作为细胞或（iii）生物活性分子递送载体，以及；（iv）联合方法。通过将水凝胶的结构特性与其治疗功能联系起来，特别关注免疫药理学刺激，这可能会加速功能性水凝胶用于SCI以及下一代中枢神经系统再生疗法的进一步发展。
