Mauck Robert L, Burdick Jason A
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 424 Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA, 19104, USA,
Ann Biomed Eng. 2015 Mar;43(3):529-42. doi: 10.1007/s10439-015-1249-z. Epub 2015 Feb 4.
When the field of tissue engineering first arose, scaffolds were conceived of as inert three-dimensional structures whose primary function was to support cellularity and tissue growth. Since then, advances in scaffold and biomaterial design have evolved to not only guide tissue formation, but also to interact dynamically with and manipulate the wound environment. At present, these efforts are being directed towards strategies that directly address limitations in endogenous wound repair, with the goal of reprogramming the local wound environment (and the cells within that locality) from a state that culminates in an inferior tissue repair into a state in which functional regeneration is achieved. This review will address this approach with a focus on recent advances in scaffold design towards the resolution of tears of the knee meniscus as a case example. The inherent limitations to endogenous repair will be discussed, as will specific examples of how biomaterials are being designed to overcome these limitations. Examples will include design of fibrous scaffolds that promote colonization by modulating local extracellular matrix density and delivering recruitment factors. Furthermore, we will discuss scaffolds that are themselves modulated by the wound environment to alter porosity and modulate therapeutic release through precise coordination of scaffold degradation. Finally, we will close with emerging concepts in local control of cell mechanics to improve interstitial cell migration and so advance repair. Overall, these examples will illustrate how emergent features within a biomaterial can be tuned to manipulate and harness the local tissue microenvironment in order to promote robust regeneration.
当组织工程领域最初兴起时，支架被认为是惰性的三维结构，其主要功能是支持细胞生长和组织形成。从那时起，支架和生物材料设计的进展不仅发展到能够引导组织形成，还能与伤口环境动态相互作用并对其进行调控。目前，这些努力正朝着直接解决内源性伤口修复局限性的策略发展，目标是将局部伤口环境（以及该局部区域内的细胞）从导致劣质组织修复的状态重新编程为实现功能性再生的状态。本综述将以膝关节半月板撕裂修复为例，重点探讨支架设计的最新进展，阐述这种方法。我们将讨论内源性修复的固有局限性，以及生物材料如何设计以克服这些局限性的具体实例。实例将包括通过调节局部细胞外基质密度和递送募集因子来促进细胞定植的纤维支架设计。此外，我们还将讨论受伤口环境调节以改变孔隙率并通过精确协调支架降解来调节治疗性释放的支架。最后，我们将以局部控制细胞力学以改善间质细胞迁移从而推进修复的新兴概念作为结尾。总体而言，这些实例将说明如何调整生物材料中的新兴特性以操纵和利用局部组织微环境，从而促进强大的再生。
