Hermans Bob P, Vos Shoko, Li Wilson W L, van der Heijden Erik H F M, van Goor Harry, Verhagen Ad F T M, Ten Broek Richard P G
Department of Cardio-Thoracic Surgery, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pathology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
J Thorac Dis. 2025 Apr 30;17(4):2140-2158. doi: 10.21037/jtd-24-1733. Epub 2025 Apr 28.
A lung sealant based on a porcine gelatin carrier impregnated with N-hydroxysuccinimide ester functionalized poly(2)oxazolines (NHS-POx) and nucleophilically activated polyoxazolines (NU-POx) was shown to be efficacious for lung sealing and . In the current study, we investigated the local biocompatibility by assessing inflammation, healing, and biodegradability in an ovine model of superficial parenchymal lung injury.
Three groups, NHS-POx, fibrin patch (TachoSil) and untreated control, are randomly applied to superficial lesions (3 mm depth) on the right lung (n=3/lung) of adult female domestic sheep, which are sacrificed for blinded histological assessment at 5, 14, and 42 days (n=4 animals per term). Semi-quantitative scoring (scale 0-4) was performed on immune cell subtypes (polymorphonuclear cells, lymphocytes, plasma cells, macrophages, giant cells, necrosis) and biomaterial response (fibrosis, neovascularization, fatty infiltrate). Post-hoc analysis was performed for a suspected labeling mistake and adapted datasets were obtained (6 weeks).
The total cell response score was significantly higher for NHS-POx control [score: 11.5 (range, 9-13) 7 (range, 6-8), P=0.005] at 5 days, and for fibrin patch control [score: 14 (range, 12-17) 7 (range, 5-8), P=0.02] at 2 weeks. At 6 weeks, cell response was similar between groups (P=0.22), with outliers due to granulomatous inflammation to residual patch (n=1 fibrin patch and n=1 mix-up sample likely fibrin patch). Wound healing, fibrosis, and neovascularization were similar across groups, showing local pleural thickening. NHS-POx patch showed mesothelial coverage at 2 weeks and was macro- and microscopically completely degraded at 6 weeks with replacement of the patch material with extracellular matrix (adapted data).
The NHS-POx patch shows a comparable to favorable biocompatibility profile compared to fibrin patch, and is a potent candidate for clinical lung sealing applications.
一种基于猪明胶载体的肺密封剂，其浸渍有N-羟基琥珀酰亚胺酯功能化聚（2）恶唑啉（NHS-POx）和亲核活化聚恶唑啉（NU-POx），已被证明对肺密封有效。在本研究中，我们通过评估成年雌性家羊浅表实质肺损伤模型中的炎症、愈合和生物降解性来研究局部生物相容性。
将三组，即NHS-POx组、纤维蛋白贴片（TachoSil）组和未处理对照组，随机应用于成年雌性家羊右肺（每只肺n = 3）的浅表损伤（深度3 mm），在5天、14天和42天处死动物（每个时间段n = 4只动物）以进行盲法组织学评估。对免疫细胞亚型（多形核细胞、淋巴细胞、浆细胞、巨噬细胞、巨细胞、坏死）和生物材料反应（纤维化、新生血管形成、脂肪浸润）进行半定量评分（0 - 4级）。对一个疑似标记错误进行事后分析并获得调整后的数据集（6周）。
在5天时，NHS-POx组的总细胞反应评分显著高于对照组[评分：11.5（范围9 - 13）对7（范围6 - 8），P = 0.005]；在2周时，纤维蛋白贴片组的总细胞反应评分显著高于对照组[评分：14（范围12 - 17）对7（范围5 - 8），P = 0.02]。在6周时，各组之间的细胞反应相似（P = （此处原文可能有误，推测为P = 0.22）），由于对残留贴片的肉芽肿性炎症导致有异常值（n = 1个纤维蛋白贴片和n = 1个可能为纤维蛋白贴片的混淆样本）。各组之间的伤口愈合、纤维化和新生血管形成相似，均表现为局部胸膜增厚。NHS-POx贴片在2周时显示有间皮覆盖，在6周时在宏观和微观上完全降解，贴片材料被细胞外基质替代（调整后数据）。
与纤维蛋白贴片相比，NHS-POx贴片显示出相当良好的生物相容性，是临床肺密封应用的有力候选材料。
