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The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model
Tissue Engineering, Part C: Methods ( IF 3 ) Pub Date : 2021-10-15 , DOI: 10.1089/ten.tec.2021.0163
Rachel Beatty 1, 2 , Chuan-En Lu 3, 4 , Julia Marzi 3, 4, 5, 6 , Ruth E Levey 1 , Daniel Carvajal Berrio 3, 4, 5 , Giulia Lattanzi 1 , Robert Wylie 1 , Raymond O'Connor 1 , Eimear Wallace 1 , Giulio Ghersi 6, 7 , Monica Salamone 6, 7 , Eimear B Dolan 1, 8 , Shannon L Layland 3, 4 , Katja Schenke-Layland 3, 4, 5, 6 , Garry P Duffy 1, 2, 9
Affiliation  

Advancements in type 1 diabetes mellitus treatments have vastly improved in recent years. The move toward a bioartificial pancreas and other fully implantable systems could help restore patient's glycemic control. However, the long-term success of implantable medical devices is often hindered by the foreign body response. Fibrous encapsulation “walls off” the implant to the surrounding tissue, impairing its functionality. In this study we aim to examine how streptozotocin-induced diabetes affects fibrous capsule formation and composition surrounding implantable drug delivery devices following subcutaneous implantation in a rodent model. After 2 weeks of implantation, the fibrous capsule surrounding the devices were examined by means of Raman spectroscopy, micro-computed tomography (μCT), and histological analysis. Results revealed no change in mean fibrotic capsule thickness between diabetic and healthy animals as measured by μCT. Macrophage numbers (CCR7 and CD163 positive) remained similar across all groups. True component analysis also showed no quantitative difference in the alpha-smooth muscle actin and extracellular matrix proteins. Although principal component analysis revealed significant secondary structural difference in collagen I in the diabetic group, no evidence indicates an influence on fibrous capsule composition surrounding the device. This study confirms that diabetes did not have an effect on the fibrous capsule thickness or composition surrounding our implantable drug delivery device.

中文翻译:

在糖尿病啮齿动物模型中对可植入治疗储液器的异物反应

近年来,1 型糖尿病治疗取得了巨大进步。转向生物人工胰腺和其他完全植入式系统可以帮助恢复患者的血糖控制。然而,植入式医疗器械的长期成功往往受到异物反应的阻碍。纤维包封将植入物与周围组织“隔开”,损害其功能。在这项研究中,我们旨在检查链脲佐菌素诱导的糖尿病如何影响在啮齿动物模型中皮下植入后可植入给药装置周围的纤维囊形成和组成。植入 2 周后,通过拉曼光谱、显微计算机断层扫描 (μCT) 和组织学分析检查装置周围的纤维囊。结果显示,通过 μCT 测量,糖尿病动物和健康动物之间的平均纤维化囊厚度没有变化。巨噬细胞数量(CCR7 和 CD163 阳性)在所有组中保持相似。真成分分析也显示 α-平滑肌肌动蛋白和细胞外基质蛋白没有定量差异。尽管主成分分析显示糖尿病组中 I 型胶原的二级结构存在显着差异,但没有证据表明对装置周围的纤维囊成分有影响。这项研究证实,糖尿病对我们植入式给药装置周围的纤维囊厚度或成分没有影响。巨噬细胞数量(CCR7 和 CD163 阳性)在所有组中保持相似。真成分分析也显示 α-平滑肌肌动蛋白和细胞外基质蛋白没有定量差异。尽管主成分分析显示糖尿病组中 I 型胶原的二级结构存在显着差异,但没有证据表明对装置周围的纤维囊成分有影响。这项研究证实,糖尿病对我们植入式给药装置周围的纤维囊厚度或成分没有影响。巨噬细胞数量(CCR7 和 CD163 阳性)在所有组中保持相似。真成分分析也显示 α-平滑肌肌动蛋白和细胞外基质蛋白没有定量差异。尽管主成分分析显示糖尿病组中 I 型胶原的二级结构存在显着差异,但没有证据表明对装置周围的纤维囊成分有影响。这项研究证实,糖尿病对我们植入式给药装置周围的纤维囊厚度或成分没有影响。没有证据表明对设备周围的纤维胶囊成分有影响。这项研究证实,糖尿病对我们植入式给药装置周围的纤维囊厚度或成分没有影响。没有证据表明对设备周围的纤维胶囊成分有影响。这项研究证实,糖尿病对我们植入式给药装置周围的纤维囊厚度或成分没有影响。
更新日期:2021-10-21
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