A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species.
A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species.
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DOI：
10.1016/j.biomaterials.2014.01.026
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发表时间：
2014-04
期刊：
影响因子：
14
通讯作者：
Duvall, Craig L.
中科院分区：
文献类型：
--
作者：
Martin, John R.;Gupta, Mukesh K.;Page, Jonathan M.;Yu, Fang;Davidson, Jeffrey M.;Guelcher, Scott A.;Duvall, Craig L.
可生物降解的组织工程支架通常由聚（丙交酯-共-乙交酯）（PLGA）或通过水解降解的类似聚酯制成。PLGA水解产生酸性分解产物，其触发加速的自催化降解机制，可产生生物材料分解和组织形成的不匹配速率。活性氧（ROS）是健康和疾病中细胞功能的关键介质，特别是在炎症和组织愈合部位，并且炎症和ROS的诱导是对生物材料植入的体内反应的天然组分。因此，通过细胞产生的ROS选择性降解的聚合物生物材料可能具有创建组织工程支架的潜力，该支架具有更好的组织向内生长和细胞介导的支架生物降解的匹配速率。为了探索这种方法，合成了一系列聚（硫代缩酮）（PTK）氨基甲酸酯（PTK-UR）生物材料支架，其通过ROS依赖性机制特异性降解。PTK-UR支架具有比由可水解降解的酯基二醇形成的类似聚（酯氨基甲酸酯）（PEUR）支架显著更高的压缩模量（p < 0.05）。与PEUR支架不同，PTK-UR支架在水性条件下稳定长达25周，但被ROS选择性降解，表明其生物降解仅为细胞介导的。PTK-URs的体外氧化降解速率遵循一级降解动力学，显著依赖于PTK组成（p < 0.05），并与ROS浓度相关。在皮下大鼠伤口中，PTK-UR支架支持细胞浸润和肉芽组织形成，在7周内遵循一级降解动力学，并且与PEUR支架相比，皮下伤口产生显著更大的支架。这些综合结果表明，ROS-可降解PTK-UR组织工程支架与类似的聚酯基生物材料相比具有显著优势，并提供了一种稳健的细胞可降解基质，用于引导新组织形成。
Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation.
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DOI：
10.1007/s10856-008-3460-z
发表时间：
2008-10-01
影响因子：
3.7
作者：
Hua, Nan;Sun, Jiao
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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Mikos, AG
影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.jconrel.2012.07.042
发表时间：
2012-09-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
Gupta MK;Meyer TA;Nelson CE;Duvall CL
通讯作者：
Duvall CL