Costa Ana Letícia Rodrigues, Willerth Stephanie M, de la Torre Lucimara Gaziola, Han Sang Won
Department of Materials and Bioprocesses Engineering, School of Chemical Engineering, University of Campinas, Campinas, SP, Brazil.
Department of Mechanical Engineering, University of Victoria, Victoria, BC, V8W 2Y2, Canada.
Mater Today Bio. 2022 Feb 16;13:100221. doi: 10.1016/j.mtbio.2022.100221. eCollection 2022 Jan.
Ischemia occurs when blood flow is reduced or restricted, leading to a lack of oxygen and nutrient supply and removal of metabolites in a body part. Critical limb ischemia (CLI) is a severe clinical manifestation of peripheral arterial disease. Atherosclerosis serves as the main cause of CLI, which arises from the deposition of lipids in the artery wall, forming atheroma and causing inflammation. Although several therapies exist for the treatment of CLI, pharmacotherapy still has low efficacy, and vascular surgery often cannot be performed due to the pathophysiological heterogeneity of each patient. Gene and cell therapies have emerged as alternative treatments for the treatment of CLI by promoting angiogenesis. However, the delivery of autologous, heterologous or genetically modified cells into the ischemic tissue remains challenging, as these cells can die at the injection site and/or leak into other tissues. The encapsulation of these cells within hydrogels for local delivery is probably one of the promising options today. Hydrogels, three-dimensional (3D) cross-linked polymer networks, enable manipulation of physical and chemical properties to mimic the extracellular matrix. Thus, specific biostructures can be developed by adjusting prepolymer properties and encapsulation process variables, such as viscosity and flow rate of fluids, depending on the final biomedical application. Electrostatic droplet extrusion, micromolding, microfluidics, and 3D printing have been the most commonly used technologies for cell encapsulation due to their versatility in producing different hydrogel-based systems (e.g., microgels, fibers, vascularized architectures and perfusable single vessels) with great potential to treat ischemic diseases. This review discusses the cell encapsulation technologies associated with hydrogels which are currently used for advanced therapies applied to limb ischemia, describing their principles, advantages, disadvantages, potentials, and innovative therapeutic ideas.
当血流减少或受限，导致身体某部位氧气和营养供应不足以及代谢产物清除受阻时，就会发生缺血。严重肢体缺血（CLI）是外周动脉疾病的一种严重临床表现。动脉粥样硬化是CLI的主要病因，它源于脂质在动脉壁沉积，形成动脉粥样瘤并引发炎症。尽管有多种治疗CLI的方法，但药物治疗效果仍然较低，而且由于每个患者的病理生理异质性，往往无法进行血管手术。基因治疗和细胞治疗已成为通过促进血管生成来治疗CLI的替代疗法。然而，将自体、异体或基因改造细胞递送至缺血组织仍然具有挑战性，因为这些细胞可能在注射部位死亡和/或渗漏到其他组织中。将这些细胞封装在水凝胶中进行局部递送可能是目前有前景的选择之一。水凝胶是三维（3D）交联聚合物网络，能够操控其物理和化学性质以模拟细胞外基质。因此，可以通过调整预聚物性质和封装工艺变量（如流体的粘度和流速）来开发特定的生物结构，这取决于最终的生物医学应用。静电液滴挤压、微成型、微流控和3D打印由于能够灵活生产不同的基于水凝胶的系统（如微凝胶、纤维、血管化结构和可灌注的单血管），且具有治疗缺血性疾病的巨大潜力，已成为最常用的细胞封装技术。本文综述了目前用于肢体缺血的先进疗法中与水凝胶相关的细胞封装技术，描述了它们的原理、优点、缺点、潜力和创新治疗理念。
