Influence of diabetes on the foreign body response to nitric oxide-releasing implants.
Influence of diabetes on the foreign body response to nitric oxide-releasing implants.
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DOI：
10.1016/j.biomaterials.2017.11.044
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发表时间：
2018-03
期刊：
影响因子：
14
通讯作者：
Schoenfisch MH
中科院分区：
文献类型：
--
作者：
Soto RJ;Merricks EP;Bellinger DA;Nichols TC;Schoenfisch MH
通过评价炎症、胶原囊形成和血管生成，比较了健康和链脲佐菌素诱导的糖尿病猪对释放一氧化氮（NO）皮下植入物的异物反应（FBR）。首先用具有不同NO释放动力学（NO通量和释放持续时间分别为0.8-630.0 pmol cm-2 s-1和2-13 d）的聚氨酯膜对钢丝基材进行改性。将NO释放材料植入皮下3、10或25 d，对FBR进行组织学和免疫组织化学评价。延迟的、更严重的炎症反应控制（即，非NO释放）植入物相对于健康猪在糖尿病猪中观察到。无论动物疾病状态如何，与对照组相比，在第3天和第10天，测试的每个NO释放植入物引起炎症减少。然而，只有能够持续7-13 d释放低NO通量（0.8-3.3 pmol cm-2 s-1）的NO释放材料在25 d时减轻了炎症反应。使用内皮细胞表面标记CD-31的免疫组织化学染色，我们还观察到糖尿病猪中非NO释放植入物的血管发育不良。相对于对照组，NO释放植入物与最长的NO释放持续时间（13天）增加血管密度的47.1%和70.4%，分别在健康和糖尿病猪。在健康模型中，组织周围的长期NO释放材料含有稀疏量的胶原蛋白，而植入物与较短的NO释放持续时间（2，3，和7天）的特点是与致密的胶原蛋白封装层，类似于控制。糖尿病猪的胶原沉积受到抑制，不受NO的影响。这些结果强调了急性发作糖尿病背景下FBR的几个关键差异。NO释放抵消糖尿病猪中更严重的FBR同时促进组织整合的观察结果可能有助于指导医疗植入物的设计（例如，葡萄糖传感器），具有用于糖尿病管理的改进的性能。
The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8–630.0 pmol cm−2 s−1 and 2–13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8–3.3 pmol cm−2 s−1) for 7–13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management.
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