Constructive Remodeling of Biologic Scaffolds is Dependent on Early Exposure to Physiologic Bladder Filling in a Canine Partial Cystectomy Model
Constructive Remodeling of Biologic Scaffolds is Dependent on Early Exposure to Physiologic Bladder Filling in a Canine Partial Cystectomy Model
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DOI：
10.1016/j.jss.2009.02.014
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发表时间：
2010-06-15
影响因子：
2.2
通讯作者：
Badylak, Stephen F.
中科院分区：
文献类型：
--
作者：
Boruch, Alan V.;Nieponice, Alejandro;Badylak, Stephen F.
由细胞外基质（ECM）组成的生物支架已被用于促进几种组织类型的建设性重塑。以往的研究表明，ECM支架重塑过程依赖于微环境因素，包括组织特异性生物力学载荷。本研究的目的是评估长期导管插入术（LTC）及其相关的膀胱充盈抑制和生理生物力学负荷对犬模型中部分膀胱切除后ECM支架重塑的影响。使用由猪小肠粘膜下层（SIS）或猪膀胱基质（UBM）制备的ECM支架进行部分膀胱部位的重建。将动物随机分为长期导管组（LTC，n = 5）和短期导管组（STC，n = 5），分别于术后4周和12周观察支架重建情况。4周时，STC组动物显示发育良好且高度分化的尿路上皮，强大的血管化网络，丰富的平滑肌肌动蛋白（SMA）和平滑肌肌球蛋白重链（smMHC）表达梭形细胞，以及许多与新形成的小动脉相关的神经元突起。相反，在4周时，LTC动物中的支架没有上皮化，并且不表达神经元标记物。LTC组中的支架形成了含有SMA +、smMHC-、纺锤形细胞的致密肉芽组织，这些细胞在形态学和表型上与肌成纤维细胞一致，但不与平滑肌细胞一致。术后12周，STC动物的ECM支架显示出建设性的重塑反应，在重塑支架内有分化的尿路上皮和平滑肌细胞岛。相比之下，在12周时，LTC动物的支架具有与纤维化更一致的重塑反应，即使导管在8周前被移除。这些发现表明，早期暴露于适当部位的机械载荷（即，膀胱充盈）在犬部分膀胱炎模型中介导ECM修复后的建设性重塑反应。(C)2010年爱思唯尔公司All rights reserved.
Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the constructive remodeling of several tissue types. Previous studies suggest that the ECM scaffold remodeling process is dependent on microenvironmental factors, including tissue-specific biomechanical loading. The objective of the present study was to evaluate the effects of long-term catheterization (LTC), with its associated inhibition of bladder filling and physiologic biomechanical loading, on ECM scaffold remodeling following partial cystectomy in a canine model. Reconstruction of the partial cystectomy site was performed using ECM scaffolds prepared from porcine small intestinal submucosa (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to either a long-term catheterization (LTC) group (n = 5, catheterized 28 d) or a short-term catheterization group (STC, n = 5, catheterized 24h), and scaffold remodeling was assessed by histologic methods at 4 and 12 wk post-operatively. By 4 wk, animals in the STC group showed a well-developed and highly differentiated urothelium, a robust vascularization network, abundant smooth muscle actin (SMA), and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and many neuronal processes associated with newly formed arterioles. In contrast, at 4 wk the scaffolds in LTC animals were not epithelialized, and did not express neuronal markers. The scaffolds in the LTC group developed a dense granulation tissue containing SMA +, smMHC-, spindle-shaped cells that were morphologically and phenotypically consistent with myofibroblasts, but not smooth muscle cells. By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a constructive remodeling response, with a differentiated urothelium and islands of smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the scaffolds in LTC animals had a remodeling response more consistent with fibrosis even though catheters had been removed 8 wk earlier. These findings show that early exposure of site-appropriate mechanical loading (Le., bladder filling) mediates a constructive remodeling response after ECM repair in a canine partial cystectomy model. (C) 2010 Elsevier Inc. All rights reserved.