Armitage Oliver E, Oyen Michelle L
Department of Engineering, University of Cambridge, Cambridge, UK.
Adv Exp Med Biol. 2015;881:187-204. doi: 10.1007/978-3-319-22345-2_11.
The musculoskeletal system is comprised of three distinct tissue categories: structural mineralized tissues, actuating muscular soft tissues, and connective tissues. Where connective tissues - ligament, tendon and cartilage - meet with bones, a graded interface in mechanical properties occurs that allows the transmission of load without creating stress concentrations that would cause tissue damage. This interface typically occurs over less than 1 mm and contains a three order of magnitude difference in elastic stiffness, in addition to changes in cell type and growth factor concentrations among others. Like all engineered tissues, the replication of these interfaces requires the production of scaffolds that will provide chemical and mechanical cues, resulting in biologically accurate cellular differentiation. For interface tissues however, the scaffold must provide spatially graded chemical and mechanical cues over sub millimetre length scales. Naturally, this complicates the manufacture of the scaffolds and every stage of their subsequent cell seeding and growth, as each region has different optimal conditions. Given the higher degree of difficulty associated with replicating interface tissues compared to surrounding homogeneous tissues, it is likely that the development of complex musculoskeletal tissue systems will continue to be limited by the engineering of connective tissues interfaces with bone.
结构性矿化组织、驱动性肌肉软组织和结缔组织。在结缔组织（韧带、肌腱和软骨）与骨骼的连接处，会出现机械性能的梯度界面，该界面能够传递负荷而不产生会导致组织损伤的应力集中。这种界面通常出现在不到1毫米的范围内，除了细胞类型和生长因子浓度等方面的变化外，其弹性刚度还存在三个数量级的差异。与所有工程组织一样，这些界面的复制需要生产能够提供化学和机械信号的支架，从而实现生物学上准确的细胞分化。然而，对于界面组织来说，支架必须在亚毫米长度尺度上提供空间梯度的化学和机械信号。自然地，这使得支架的制造以及随后细胞接种和生长的每个阶段都变得复杂，因为每个区域都有不同的最佳条件。鉴于与复制周围均匀组织相比，复制界面组织的难度更高，复杂肌肉骨骼组织系统的发展可能会继续受到结缔组织与骨骼界面工程的限制。
