Qu Dovina, Mosher Christopher Z, Boushell Margaret K, Lu Helen H
Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Avenue, 351 Engineering Terrace, MC 8904, New York, NY, 10027, USA.
Ann Biomed Eng. 2015 Mar;43(3):697-717. doi: 10.1007/s10439-014-1190-6. Epub 2014 Dec 3.
The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will enable integrative and functional repair of soft tissue injuries, and moreover, lay the foundation for the development of composite tissue systems and ultimately, total limb or joint regeneration.
再生工程当前面临的主要挑战在于同时形成不止一种类型的组织，并将它们功能性地组装成复杂的组织或器官系统。组织与组织之间的同步性在肌肉骨骼系统中尤为重要，在该系统中，整体器官功能是通过骨骼与韧带、肌腱或软骨等软组织的无缝整合以及肌肉与肌腱的整合来实现的。因此，与传统的单一组织系统（如骨骼、韧带）不同，用于功能性结缔组织单元（如骨 - 韧带 - 骨）再生的复合组织支架设计正在积极研究中。与之密切相关的是重新建立组织与组织界面的努力，这对于连接这些组织构建块并促进宿主整合至关重要。该领域前沿的许多研究都集中在受生物启发的分层或梯度支架设计上，其目的是重现不同组织区域固有的结构和成分不均匀性。因此，鉴于这些肌肉骨骼组织单元的复杂性，关键问题是如何在支架设计中确定最相关的参数以重现天然的结构 - 功能关系。因此，本综述的重点除了介绍复杂支架设计的最新进展外，还在于探索如何将策略性仿生应用于工程组织连接性。策略性仿生的目标是通过确定需要从自然界学习的内容并定义支架设计中必须重现的基本基质特征来避免过度工程化。本综述将讨论这种工程策略在最常见的肌肉骨骼组织单元（如骨 - 韧带 - 骨、肌肉 - 肌腱 - 骨、软骨 - 骨）再生中的应用。预计这些令人兴奋的努力将实现软组织损伤的综合和功能性修复，此外，为复合组织系统的发展奠定基础，并最终实现全肢体或关节再生。
