Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair.
Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair.
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DOI：
10.1002/jor.23842
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Gelberman RH
中科院分区：
文献类型：
--
作者：
Linderman SW;Shen H;Yoneda S;Jayaram R;Tanes ML;Sakiyama-Elbert SE;Xia Y;Thomopoulos S;Gelberman RH
最近的生长因子，细胞和支架为基础的实验干预滑膜内屈肌腱修复已证明在啮齿动物模型的治疗潜力。然而，由于对递送材料的有害炎症反应和靶向生物愈合反应的诱导不足，这些方法在大型动物试验中没有实现一致的功能改善。在这项研究中，我们实现了基于多孔缝线的结缔组织生长因子（CTGF）持续输送到屈肌腱在临床相关的犬模型。基于修复后14天的组织学、基因表达或蛋白质组学分析，使用CTGF负载缝线进行的修复具有机械性能，并且未显示任何粘连或其他阴性炎症反应的证据。负载CTGF的缝线诱导局部细胞浸润和紧邻缝线的显著生物学反应，包括血管生成和胶原沉积的组织学体征。在整个肌腱物质中没有明显的广泛生物学效应。巨噬细胞标志物CD 163和抗凋亡因子BCL 2L 1的基因表达存在显著差异;然而，这些差异未得到蛋白质组学分析的证实。总之，本研究提供了令人鼓舞的证据，证明多孔缝线可持续释放生物活性CTGF，且无阴性炎症反应迹象。随着产生积极的局部生物学反应的安全有效方法的发展，未来的研究可以探索其他方法来增强滑膜内肌腱修复。
Recent growth factor, cell, and scaffold-based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture-based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF-laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF-laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti-apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair.
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影响因子：
0.1
作者：
Linderman SW;Gelberman RH;Thomopoulos S;Shen H
通讯作者：
Shen H
影响因子：
--
作者：
Fuchs, T. F.;Surke, C.;Schmidmaier, G.
通讯作者：
Schmidmaier, G.
DOI：
10.1002/jor.23064
发表时间：
2016-04
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Gelberman RH;Shen H;Kormpakis I;Rothrauff B;Yang G;Tuan RS;Xia Y;Sakiyama-Elbert S;Silva MJ;Thomopoulos S
通讯作者：
Thomopoulos S
影响因子：
1.9
作者：
ABRAHAMSSON, SO;GELBERMAN, RH;LOHMANDER, SL
通讯作者：
LOHMANDER, SL
影响因子：
9.7
作者：
Linderman, Stephen W.;Kormpakis, Ioannis;Thomopoulos, Stavros
通讯作者：
Thomopoulos, Stavros