Ectopic tissue engineered ligament with silk collagen scaffold for ACL regeneration: A preliminary study

被引:22
作者
Ran, Jisheng [1 ,3 ]
Hu, Yejun [1 ,2 ]
Le, Huihui [1 ,3 ]
Chen, Yangwu [1 ,2 ,3 ]
Zheng, Zefeng [1 ]
Chen, Xiao [2 ]
Yin, Zi [2 ]
Yan, Ruijian [1 ,3 ]
Jin, Zhangchu [1 ,2 ,3 ]
Tang, Chenqi [1 ,2 ,3 ]
Huang, Jiayun [1 ,2 ,3 ]
Gu, Yanjia [1 ,2 ,3 ]
Xu, Langhai [1 ,3 ]
Qian, Shengjun [1 ,3 ]
Zhang, Wei [1 ,3 ]
Heng, Boon Chin [4 ]
Dominique, Pioletti [5 ]
Chen, Weishan [1 ,3 ]
Wu, Lidong [1 ,3 ]
Shen, Weiliang [1 ,2 ,3 ,6 ]
Ouyang, Hongwei [2 ,6 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Orthoped Surg, 88 Jie Fang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Dr Li Dak Sum & Yip Yio Chin Ctr Stem Cells & Reg, Hangzhou, Zhejiang, Peoples R China
[3] Zhejiang Univ, Orthopaed Res Inst, Hangzhou, Zhejiang, Peoples R China
[4] Univ Hong Kong, Fac Dent, Dept Endodontol, Pokfulam, Hong Kong, Peoples R China
[5] Ecole Polytech Fed Lausanne, Lab Biomech Orthoped, Lausanne, Switzerland
[6] China Orthopaed Regenerat Med CORMed, Hangzhou, Zhejiang, Peoples R China
基金
国家高技术研究发展计划(863计划);
关键词
ACL regeneration; Ectopic tissue engineered ligament; Silk collagen scaffold; Bone tunnel healing; ANTERIOR CRUCIATE LIGAMENT; MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; GROWTH-FACTOR; RABBIT MODEL; TENDON AUTOGRAFT; SKELETAL-MUSCLE; BONE-FORMATION; IN-VIVO; RECONSTRUCTION;
D O I
10.1016/j.actbio.2017.02.027
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Anterior cruciate ligament (ACL) reconstruction remains a formidable clinical challenge because of the lack of vascularization and adequate cell numbers in the joint cavity. In this study, we developed a novel strategy to mimic the early stage of repair in vivo, which recapitulated extra-articular inflammatory response to facilitate the early ingrowth of blood vessels and cells. A vascularized ectopic tissue engineered ligament (ETEL) with silk collagen scaffold was developed and then transferred to reconstruct the ACL in rabbits without interruption of perfusion. At 2 weeks after ACL reconstruction, more well-perfused cells and vessels were found in the regenerated ACL with ETEL, which decreased dramatically at the 4 and 12 week time points with collagen deposition and maturation. ACL treated with ETEL exhibited more mature ligament structure and enhanced ligament-bone healing post-reconstructive surgery at 4 and 12 weeks, as compared with the control group. In addition, the ETEL group was demonstrated to have higher modulus and stiffness than the control group significantly at 12 weeks post-reconstructive surgery. In conclusion, our results demonstrated that the ETEL can provide sufficient vascularity and cellularity during the early stages of healing, and subsequently promote ACL regeneration and ligament-bone healing, suggesting its clinic use as a promising therapeutic modality. Statement of Significance Early inflammatory cell infiltration, tissue and vessels ingrowth were significantly higher in the extra articular implanted scaffolds than theses in the joint cavity. By mimicking the early stages of wound repair, which provided extra-articular inflammatory stimulation to facilitate the early ingrowth of blood vessels and cells, a vascularized ectopic tissue engineered ligament (ETEL) with silk collagen scaffold was constructed by subcutaneous implantation for 2 weeks. The fully vascularized TE ligament was then transferred to rebuild ACL without blood perfusion interruption, and was demonstrated to exhibit improved ACL regeneration, bone tunnel healing and mechanical properties. (C) 2017 Published by Elsevier Ltd on behalf of Acta Materialia Inc.
引用
收藏
页码:307 / 317
页数:11
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