Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration.
Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration.
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DOI：
10.3390/ijms222111372
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发表时间：
2021-10-21
影响因子：
5.6
通讯作者：
Modo M
中科院分区：
文献类型：
--
作者：
Damian C;Ghuman H;Mauney C;Azar R;Reinartz J;Badylak SF;Modo M
细胞外基质(ECM)水凝胶促进中风后病变腔内的组织再生。然而，生物支架的再生潜力需要在中风引起的病理环境演变的背景下考虑。为了在大鼠中评估这一关键问题，在卒中后7天、14天、28天和90天将ECM水凝胶注射到病变核心/腔内。由于卒中后7天缺乏组织空化，ECM水凝胶植入没有达到足够的体积和分布，因此无法与其他时间点进行比较。卒中后14天和28天植入ECM水凝胶的生物降解率在生物支架植入后14天有效(80%)，而卒中后90天植入的ECM水凝胶生物降解率仅为60%。巨噬细胞侵袭在卒中后14天和28天表现强劲，但在卒中后90天则减弱。在所有时间点，促炎症(M1)和促修复(M2)表型比率相同，这表明病理环境决定巨噬细胞的侵袭，而ECM水凝胶则定义了它们的极化。神经细胞(神经前体细胞、神经元、星形胶质细胞、少突胶质细胞)在所有时间点均可见，但卒中后90天植入会导致成熟表型密度降低。因此，脑组织修复依赖于将生物支架有效地输送到组织腔中，中风后28天产生最有效的生物降解和组织再生，而中风后90天，这些影响显著减少。因此，提高我们对病理环境如何影响生物降解和组织修复过程的理解，对于设计能够延长生物支架修复受损大脑的治疗窗口的工程策略至关重要。
Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.
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影响因子：
14
作者：
Jin T;Nicholls FJ;Crum WR;Ghuman H;Badylak SF;Modo M
通讯作者：
Modo M
DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
影响因子：
2
作者：
Gregersen, R;Christensen, T;Finsen, B
通讯作者：
Finsen, B
影响因子：
5.7
作者：
Ghuman, Harmanvir;Hitchens, T. Kevin;Modo, Michel
通讯作者：
Modo, Michel
影响因子：
14
作者：
Brown, Bryan N.;Valentin, Jolene E.;Stewart-Akers, Ann M.;McCabe, George P.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.