Hart David A, Nakamura Norimasa, Shrive Nigel G
Department of Surgery, Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.
Bone and Joint Health Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada.
Front Bioeng Biotechnol. 2021 Sep 28;9:760273. doi: 10.3389/fbioe.2021.760273. eCollection 2021.
Musculoskeletal (MSK) tissues such as articular cartilage, menisci, tendons, and ligaments are often injured throughout life as a consequence of accidents. Joints can also become compromised due to the presence of inflammatory diseases such as rheumatoid arthritis. Thus, there is a need to develop regenerative approaches to address such injuries to heterogeneous tissues and ones that occur in heterogeneous environments. Such injuries can compromise both the biomechanical integrity and functional capability of these tissues. Thus, there are several challenges to overcome in order to enhance success of efforts to repair and regenerate damaged MSK tissues. 1. MSK tissues arise during development in very different biological and biomechanical environments. These early tissues serve as a template to address the biomechanical requirements evolving during growth and maturation towards skeletal maturity. Many of these tissues are heterogeneous and have transition points in their matrix. The heterogeneity of environments thus presents a challenge to replicate with regard to both the cells and the ECM. 2. Growth and maturation of musculoskeletal tissues occurs in the presence of anabolic mediators such as growth hormone and the IGF-1 family of proteins which decline with age and are low when there is a greater need for the repair and regeneration of injured or damaged tissues with advancing age. Thus, there is the challenge of re-creating an anabolic environment to enhance incorporation of implanted constructs. 3. The environments associated with injury or chronic degeneration of tissues are often catabolic or inflammatory. Thus, there is the challenge of creating a more favorable in vivo environment to facilitate the successful implantation of in vitro engineered constructs to regenerate damaged tissues. The goal of regenerating MSK tissues has to be to meet not only the biological requirements (components and structure) but also the heterogeneity of function (biomechanics) in vivo. Furthermore, for many of these tissues, the regenerative approach has to overcome the site of injury being influenced by catabolism/inflammation. Attempts to date using both endogenous cells, exogenous cells and scaffolds of various types have been limited in achieving long term outcomes, but progress is being made.
肌肉骨骼（MSK）组织，如关节软骨、半月板、肌腱和韧带，在一生中常因意外事故而受损。由于类风湿性关节炎等炎症性疾病的存在，关节也可能受到损害。因此，需要开发再生方法来应对此类异质性组织以及在异质性环境中发生的损伤。此类损伤会损害这些组织的生物力学完整性和功能能力。因此，为提高受损MSK组织修复和再生的成功率，有几个挑战需要克服。1. MSK组织在发育过程中出现在非常不同的生物和生物力学环境中。这些早期组织作为模板，以满足生长和成熟至骨骼成熟过程中不断演变的生物力学需求。这些组织中的许多都是异质性的，并且在其基质中有过渡点。因此，环境的异质性对细胞和细胞外基质（ECM）的复制都构成了挑战。2. 肌肉骨骼组织的生长和成熟发生在合成代谢介质如生长激素和IGF-1蛋白家族存在的情况下，这些介质会随着年龄增长而下降，并且在随着年龄增长对受损或损伤组织进行修复和再生的需求更大时处于低水平。因此，重建合成代谢环境以增强植入构建体的整合是一项挑战。3. 与组织损伤或慢性退变相关的环境通常是分解代谢或炎症性的。因此，创建一个更有利的体内环境以促进体外工程构建体成功植入以再生受损组织是一项挑战。再生MSK组织的目标不仅要满足生物学要求（成分和结构），还要满足体内功能的异质性（生物力学）。此外，对于许多此类组织，再生方法必须克服损伤部位受到分解代谢/炎症影响的问题。迄今为止，使用内源性细胞、外源性细胞和各种类型支架的尝试在实现长期效果方面受到限制，但正在取得进展。
