Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair
Alignment of collagen fiber in knitted silk scaffold for functional massive rotator cuff repair
复制标题
针织丝支架中胶原纤维的排列用于功能性大面积肩袖修复
DOI：
10.1016/j.actbio.2017.01.041
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发表时间：
2017
影响因子：
9.7
通讯作者：
Heng Boon Ch
中科院分区：
文献类型：
--
作者：
Zheng Zefeng;Hu Yejun;Chen Xiao;Yin Zi;Shen Weiliang;Ouyang Hong-Wei;Zheng Zefeng;Ran Jisheng;Chen Weishan;Hu Yejun;Zhu Ting;Feng Gang;Le Huihui;Tang Chenqi;Huang Jiayun;Chen Yangwu;Shen Weiliang;Chen Xiao;Yin Zi;Shen Weiliang;Ouyang Hong-Wei;Heng Boon Ch
肩袖撕裂是最常见的肩部损伤类型之一，通常会导致疼痛和身体虚弱。同种异体肌腱来源的脱细胞基质没有合适的孔径和孔隙率来促进细胞渗透，而商业上可用的合成支架通常不足以诱导肌腱分化。本研究的目的是开发一种先进的三维定向胶原/丝素支架(ACS)，并观察其在兔肩袖撕裂模型中的效果。ACS具有与天然肌腱相似的三维胶原纤维排列，具有优越的力学特性。在异位移植研究的基础上，确定了维持稳定的有利于细胞渗透的宏观结构所需的最佳胶原浓度(10 mg/ml)、孔径(108.43±72.25μm)和孔隙率(97.94±30.08%)。在体外培养条件下，肌腱干/祖细胞(TSPC)呈纺锤形形态，早在24 h就在ACS上排列整齐，7天后形成细胞间接触并沉积细胞外基质。在活体肩袖修复模型中，植入后12周，急性冠脉综合征组的再生腱显示出更明显的自然微结构，胶原纤维直径(48.72±3.75比44.26±55.03)nm，具有更好的排列和力学性能(139.85±49.36比99.09±33.98)。综上所述，这些发现证明了大孔3D排列支架在促进肩袖肌腱再生方面的积极效果，以及它在肩袖肌腱组织工程中的实际应用。意义陈述肩袖撕裂是最常见的肩部损伤之一，给骨科医生带来了巨大的临床挑战。肌腱组织工程有可能克服这一问题。然而，更有效的修复肩袖肌腱损伤的支架材料还有待开发，这些支架具有良好的生物相容性、合适的孔径、良好的诱导性和足够的机械强度。在这项研究中，我们开发了一种新型的大孔3D排列的胶原/丝素支架，并证明了这种新型支架通过诱导类似自然肌腱的排列的细胞上结构，进而促进来自肌腱本身和周围组织的干/祖细胞的细胞渗透和肌腱分化，从而增强了肩袖肌腱再生的效果。因此，它在肌腱组织工程中具有潜在的临床应用价值。
Rotator cuff tear is one of the most common types of shoulder injuries, often resulting in pain and physical debilitation. Allogeneic tendon-derived decellularized matrices do not have appropriate pore size and porosity to facilitate cell infiltration, while commercially-available synthetic scaffolds are often inadequate at inducing tenogenic differentiation. The aim of this study is to develop an advanced 3D aligned collagen/silk scaffold (ACS) and investigate its efficacy in a rabbit massive rotator cuff tear model. ACS has similar 3D alignment of collagen fibers as natural tendon with superior mechanical characteristics. Based on ectopic transplantation studies, the optimal collagen concentration (10 mg/ml), pore diameter (108.43 ± 7.25 μm) and porosity (97.94 ± 0.08%) required for sustaining a stable macro-structure conducive for cellular infiltration was determined. Within in vitro culture, tendon stem/progenitor cells (TSPCs) displayed spindle-shaped morphology, and were well-aligned on ACS as early as 24 h. TSPCs formed intercellular contacts and deposited extracellular matrix after 7 days. With the in vivo rotator cuff repair model, the regenerative tendon of the ACS group displayed more conspicuous native microstructures with larger diameter collagen fibrils (48.72 ± 3.75 vs. 44.26 ± 5.03 nm) that had better alignment and mechanical properties (139.85 ± 49.36 vs. 99.09 ± 33.98 N) at 12 weeks post-implantation. In conclusion, these findings demonstrate the positive efficacy of the macroporous 3D aligned scaffold in facilitating rotator cuff tendon regeneration, and its practical applications for rotator cuff tendon tissue engineering.Statement of SignificanceMassive rotator cuff tear is one of the most common shoulder injuries, and poses a formidable clinical challenge to the orthopedic surgeon. Tissue engineering of tendon can potentially overcome the problem. However, more efficacious scaffolds with good biocompatibility, appropriate pore size, favorable inductivity and sufficient mechanical strength for repairing massive rotator cuff tendon injuries need to be developed. In this study, we developed a novel macroporous 3D aligned collagen/silk scaffold, and demonstrated that this novel scaffold enhanced the efficacy of rotator cuff tendon regeneration by inducing aligned supracellular structures similar to natural tendon, which in turn enhanced cellular infiltration and tenogenic differentiation of stem/progenitor cells from both the tendon itself and surrounding tissues. Hence, it can potentially be a clinically useful application for tendon tissue engineering.