Marsico Grazia, Martin-Saldaña Sergio, Pandit Abhay
CÚRAM SFI Research Centre for Medical Devices National University of Ireland Galway Ireland.
Adv Sci (Weinh). 2021 Feb 8;8(7):2003119. doi: 10.1002/advs.202003119. eCollection 2021 Apr.
Chronic limb threatening ischemia (CLTI) is a severe condition defined by the blockage of arteries in the lower extremities that leads to the degeneration of blood vessels and is characterized by the formation of non-healing ulcers and necrosis. The gold standard therapies such as bypass and endovascular surgery aim at the removal of the blockage. These therapies are not suitable for the so-called "no option patients" which present multiple artery occlusions with a likelihood of significant limb amputation. Therefore, CLTI represents a significant clinical challenge, and the efforts of developing new treatments have been focused on stimulating angiogenesis in the ischemic muscle. The delivery of pro-angiogenic nucleic acid, protein, and stem cell-based interventions have limited efficacy due to their short survival. Engineered biomaterials have emerged as a promising method to improve the effectiveness of these latter strategies. Several synthetic and natural biomaterials are tested in different formulations aiming to incorporate nucleic acid, proteins, stem cells, macrophages, or endothelial cells in supportive matrices. In this review, an overview of the biomaterials used alone and in combination with growth factors, nucleic acid, and cells in preclinical models is provided and their potential to induce revascularization and regeneration for CLTI applications is discussed.
慢性肢体威胁性缺血（CLTI）是一种严重病症，由下肢动脉阻塞导致血管退化所定义，其特征为形成不愈合溃疡和坏死。诸如搭桥手术和血管内手术等金标准疗法旨在清除阻塞物。这些疗法不适用于所谓的“无选择患者”，这类患者存在多处动脉闭塞，有较高的肢体截肢可能性。因此，CLTI是一项重大的临床挑战，开发新治疗方法的努力一直集中在刺激缺血肌肉中的血管生成上。促血管生成核酸、蛋白质和基于干细胞的干预措施由于其存活时间短，疗效有限。工程生物材料已成为提高这些后一种策略有效性的一种有前景的方法。几种合成和天然生物材料以不同配方进行测试，旨在将核酸、蛋白质、干细胞、巨噬细胞或内皮细胞纳入支持性基质中。在本综述中，提供了在临床前模型中单独使用以及与生长因子、核酸和细胞联合使用的生物材料概述，并讨论了它们在CLTI应用中诱导血管再通和再生的潜力。
