Abstract：
Healing of a damaged tendon-to-bone enthesis occurs through the formation of fibrovascular scar tissue with greatly compromised histological and biomechanical properties instead of the regeneration of a new enthesis due to the lack of graded tissue-engineering zones in the interface during the healing process. In the present study, a structure-, composition-, and mechanics-graded biomimetic scaffold (GBS) coated with specific decellularized extracellular matrix (dECM) (GBS-E) aimed to enhance its cellular differentiation inducibilities was fabricated using a three-dimensional (3-D) bioprinting technique. In vitro cellular differentiation studies showed that from the tendon-engineering zone to the bone-engineering zone in the GBS, the tenogenic differentiation inducibility decreased in correspondence with an increase in the osteogenic differentiation inducibility. The chondrogenic differentiation inducibility peaked in the middle, which was in consistent with the graded cellular phenotypes observed in a native tendon-to-bone enthesis, while specific dECM coating from the tendon-engineering zone to the bone-engineering zone (tendon-, cartilage-, and bone-derived dECM, respectively) further enhanced its cellular differentiation inducibilities (GBS-E). In a rabbit rotator cuff tear model, histological analysis showed that the GBS-E group exhibited well-graded tendon-to-bone differentiated properties in the repaired interface that was similar to a native tendon-to-bone enthesis at 16 weeks. Moreover, the biomechanical properties in the GBS-E group were also significantly higher than those in other groups at 16 weeks. Therefore, our findings suggested a promising tissue-engineering strategy for the regeneration of a complex enthesis using a three-dimensional bioprinting technique.
摘要：
受损的腱-骨生成的愈合是通过形成具有极大损害的组织学和生物力学特性的纤维血管瘢痕组织而发生的，而不是由于在愈合过程中界面中缺乏分级的组织工程区而再生新的生成。在本研究中,一个结构-，组合-，使用三维（3-D）生物打印技术制造了涂有特定脱细胞细胞外基质（dECM）（GBS-E）的力学分级仿生支架（GBS），旨在增强其细胞分化诱导性。体外细胞分化研究表明，从GBS的肌腱工程区到骨工程区，张力分化诱导性的降低与成骨分化诱导性的增加相对应。软骨分化诱导性在中间达到峰值，这与在天然肌腱-骨骼发育中观察到的分级细胞表型一致，而从肌腱工程区到骨工程区的特定dECM涂层(肌腱-，软骨-，和骨源性dECM，分别）进一步增强了其细胞分化诱导性（GBS-E）。在兔子肩袖撕裂模型中，组织学分析显示,GBS-E组在修复界面表现出良好的腱-骨分化特性,与16周时的天然腱-骨分化相似.此外，16周时GBS-E组的生物力学特性也显著高于其他组。因此,我们的研究结果提出了一种有前景的组织工程策略，用于使用三维生物打印技术再生复杂的生育。
