Department of Biomedical Engineering, The Cleveland Clinic, 9500 Euclid Avenue, ND 20, Cleveland, OH 44195, USA.
Drug Deliv Transl Res. 2012 Oct;2(5):323-50. doi: 10.1007/s13346-012-0070-6.
Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures.
弹性蛋白是细胞外基质的重要组成部分，为柔软的结缔组织提供了变形后弹性回弹的特性，并通过生物力学转导来调节细胞反应，以维持组织内稳态。大多数成年细胞合成弹性蛋白前体并将其组装成成熟交联结构的能力有限，这阻碍了功能性组织工程构建体的发展，这些构建体在体内表现出正常天然弹性组织的结构和生物力学特性。在患病组织中，蛋白酶的慢性过度表达会导致基质的显著降解，进一步限制新沉积的弹性基质的积累和质量（例如纤维形成）。这篇综述概述了弹性蛋白和弹性基质在软组织中的作用和重要性、体外弹性基质生成和体内再生弹性基质修复的挑战、增强弹性蛋白沉积和基质组装的当前生物分子策略，以及需要同时抑制蛋白水解基质破坏以提高弹性生成的数量和质量。该综述进一步介绍了基于生物材料的选项，使用支架和纳米载体来控制这些生物分子的呈现和释放，以实现临床相关的天然弹性基质样超结构的仿生组装。最后，该综述概述了这些策略在再生组织特异性弹性基质结构和超结构方面的最新进展和应用前景。
