Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.
Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa.
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DOI：
10.1016/j.actbio.2014.11.038
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发表时间：
2015-03
影响因子：
9.7
通讯作者：
Hinds, Monica T.
中科院分区：
文献类型：
--
作者：
Glynn, Jeremy J.;Polsin, Elizabeth G.;Hinds, Monica T.
脱细胞组织已被广泛用作生物医学应用的支架，这是由于它们呈现粘附肽序列和生长因子，这有助于与周围组织整合。最常用的脱细胞组织之一来源于猪小肠粘膜下层（SIS）。在一些应用中，SIS被交联以调节支架的机械性能或降解速率。尽管SIS被广泛使用，但没有SIS血液反应的机制表征，也没有交联如何影响这些反应。因此，我们使用流动的全血表征了SIS和二甲双胍交联SIS（cSIS）对血浆凝血的影响，包括内源性和外源性凝血途径的靶向评估以及血栓形成。SIS抑制血浆凝固开始的抗凝，以及低浓度的凝血酶或组织因子。SIS使活化部分凝血活酶时间延长14.3±1.54秒，表明内源性凝血途径受到抑制。碳二亚胺交联消除了SIS的所有抗凝作用，肝素酶I和III治疗也是如此，这表明肝素和硫酸乙酰肝素主要是SIS抗凝作用的原因。抑制内源性途径的接触激活可防止cSIS介导的凝血。当管状SIS装置连接到非人灵长类动物动静脉分流回路时，其使全血能够流过装置而不使用抗凝剂，SIS显示出显著有限的血小板蓄积和纤维蛋白原掺入，而cSIS引发显著更高的血小板和纤维蛋白原蓄积。这些结果表明SIS是一种抗血栓材料，交联显著降低了SIS的血液相容性。
Decellularized tissues have been widely used as scaffolds for biomedical applications due to their presentation of adhesion peptide sequences and growth factors, which facilitate integration with surrounding tissue. One of the most commonly used decellularized tissue is derived from porcine small intestinal submucosa (SIS). In some applications, SIS is crosslinked to modulate the mechanical properties or degradation rate of the scaffold. Despite the widespread use of SIS, there has been no mechanistic characterization of blood reactions with SIS, nor how crosslinking affects these reactions. Therefore, we characterized the effect of SIS and carbodiimide-crosslinked SIS (cSIS) on plasma coagulation, including targeted assessments of the intrinsic and extrinsic coagulation pathways, and thrombus formation using flowing whole blood. SIS inhibited plasma coagulation initiated by recalcification, as well as low concentrations of thrombin or tissue factor. SIS prolonged the activated partial thromboplastin time by 14.3±1.54 sec, indicating inhibition of the intrinsic coagulation pathway. Carbodiimide crosslinking abrogated all anticoagulant effects of SIS, as did heparinase I and III treatment, suggesting heparin and heparan sulfate are predominantly responsible for SIS anticoagulant effects. Inhibiting contact activation of the intrinsic pathway prevented cSIS-mediated coagulation. When tubular SIS devices were connected to a nonhuman primate arteriovenous shunt loop, which enables whole blood to flow across devices without the use of anticoagulants, SIS demonstrated remarkably limited platelet accumulation and fibrinogen incorporation, while cSIS initiated significantly higher platelet and fibrinogen accumulation. These results demonstrate that SIS is a thromboresistant material and crosslinking markedly reduces the hemocompatibility of SIS.
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影响因子：
2.9
作者：
LINHARDT, RJ;TURNBULL, JE;GALLAGHER, JT
通讯作者：
GALLAGHER, JT
影响因子：
14
作者：
Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
DOI：
10.3109/08941939309141619
发表时间：
1993-05-01
期刊：
Journal of investigative surgery : the official journal of the Academy of Surgical Research
影响因子：
--
作者：
Lantz, G C;Badylak, S F;Morff, R J
通讯作者：
Morff, R J
影响因子：
1.9
作者：
Ansaloni, Luca;Cambrini, Paolo;Pinna, Antonio Daniele
通讯作者：
Pinna, Antonio Daniele
影响因子：
14
作者：
Jordan, Sumanas W.;Haller, Carolyn A.;Chaikof, Elliot L.
通讯作者：
Chaikof, Elliot L.