Department of Bioengineering, Imperial College London, London, SW7 2AZ,
Eur Cell Mater. 2021 May 25;41:531-545. doi: 10.22203/eCM.v041a34.
Developmental engineering strategies aim to recapitulate aspects of development in vitro as a means of forming functional engineered tissues, including cartilage and bone, for tissue repair and regeneration. Biophysical stimuli arising from fetal movements are critical for guiding skeletogenesis, but there have been few investigations of the biomechanical parameters which optimally promote cartilage and bone development events in in vitro explants. The effect of applied flexion-extension movement frequencies (0.33 and 0.67 Hz) and durations (2 h periods, 1, 2 or 3 × per day) on knee (stifle) joint cartilage shape, chondrogenesis and diaphyseal mineralisation of fetal chick hindlimbs, cultured in a mechanostimulation bioreactor, were assessed both quantitatively and qualitatively. It was hypothesised that increasing frequency and duration of movements would synergistically promote cartilage and bone formation in a dose-dependent manner. Increasing loading duration promoted cartilage growth, shape development and mineralisation of the femoral condyles and tibiotarsus. While increasing frequency had a significant positive effect on mineralisation, hyaline cartilage growth and joint shape were unaffected by frequency change within the ranges assessed, and there were limited statistical interactions between the effects of movement frequency and duration on cartilage or bone formation. Increased glycosaminoglycan deposition and cell proliferation may have contributed to the accelerated cartilage growth and shape change under increasing loading duration. The results demonstrated that frequencies and durations of applied biomechanical stimulation differentially promoted cartilage and bone formation, with implications for developmentally inspired tissue engineering strategies aiming to modulate tissue construct properties.
发育工程策略旨在体外再现发育的各个方面，从而形成功能性的工程组织，包括软骨和骨骼，用于组织修复和再生。胎儿运动产生的生物物理刺激对于指导骨骼发生至关重要，但对于最佳促进体外外植体中软骨和骨骼发育事件的生物力学参数的研究甚少。应用屈伸运动频率（0.33 和 0.67 Hz）和时长（2 h 期，每天 1、2 或 3 次）对胎儿鸡后肢膝关节（膝关节）软骨形状、软骨生成和骨干矿化的影响在机械刺激生物反应器中培养的，进行了定量和定性评估。假设增加运动的频率和时长会协同促进软骨和骨形成，呈剂量依赖性。增加加载时长促进了股骨髁和胫骨的软骨生长、形状发育和矿化。虽然增加频率对矿化有显著的积极影响，但在评估范围内，频率变化对透明软骨生长和关节形状没有影响，并且运动频率和时长对软骨或骨形成的影响之间的统计相互作用有限。增加糖胺聚糖沉积和细胞增殖可能有助于在增加加载时长下加速软骨生长和形状变化。结果表明，施加的生物力学刺激的频率和时长差异地促进了软骨和骨的形成，这对旨在调节组织构建特性的基于发育的组织工程策略具有重要意义。
