A Tissue-Engineered Muscle Repair Construct for Functional Restoration of an Irrecoverable Muscle Injury in a Murine Model
A Tissue-Engineered Muscle Repair Construct for Functional Restoration of an Irrecoverable Muscle Injury in a Murine Model
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DOI：
10.1089/ten.tea.2010.0682
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发表时间：
2011-09-01
影响因子：
4.1
通讯作者：
Christ, George J.
中科院分区：
文献类型：
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作者：
Machingal, Masood A.;Corona, Benjamin T.;Christ, George J.
对于由创伤性损伤、肿瘤切除或其他骨骼肌退行性疾病引起的肌肉体积损失（VML），没有有效的临床治疗。本研究的目的是开发和表征一种更临床相关的组织工程化肌肉修复（TE-MR）结构，用于小鼠背阔肌（LD）VML损伤的功能恢复。为此，将通过将大鼠成肌细胞接种在猪膀胱无细胞基质上而开发的TE-MR构建体在生物反应器中预处理1周，并在通过切除50%的天然LD而产生的VML损伤部位植入裸鼠中。损伤后两个月和TE-MR植入，最大强直力是在本地LD肌肉中观察到的72%相似。相比之下，未修复或仅用支架修复的受损LD肌肉在2个月后仅产生与天然LD肌肉力的50%相似的力。植入后2个月取出的LD组织的组织学分析表明TE-MR结构的重塑以及TE-MR结构内结蛋白阳性肌纤维、血管和神经血管束的存在。总体而言，这些令人鼓舞的初步观察结果证明了TE-MR结构植入后2个月内显著的功能恢复，并为该技术在鼠VML损伤模型中的适用性提供了明确的概念证据。
There are no effective clinical treatments for volumetric muscle loss (VML) resulting from traumatic injury, tumor excision, or other degenerative diseases of skeletal muscle. The goal of this study was to develop and characterize a more clinically relevant tissue-engineered muscle repair (TE-MR) construct for functional restoration of a VML injury in the mouse lattissimus dorsi (LD) muscle. To this end, TE-MR constructs developed by seeding rat myoblasts on porcine bladder acellular matrix were preconditioned in a bioreactor for 1 week and implanted in nude mice at the site of a VML injury created by excising 50% of the native LD. Two months postinjury and implantation of TE-MR, maximal tetanic force was similar to 72% of that observed in native LD muscle. In contrast, injured LD muscles that were not repaired, or were repaired with scaffold alone, produced only similar to 50% of native LD muscle force after 2 months. Histological analyses of LD tissue retrieved 2 months after implantation demonstrated remodeling of the TE-MR construct as well as the presence of desmin-positive myofibers, blood vessels, and neurovascular bundles within the TE-MR construct. Overall, these encouraging initial observations document significant functional recovery within 2 months of implantation of TE-MR constructs and provide clear proof of concept for the applicability of this technology in a murine VML injury model.