Distinct Effects of Heparin and Interleukin-4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats,Advanced Healthcare Materials

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Distinct Effects of Heparin and Interleukin-4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-09-14 , DOI: 10.1002/adhm.202101103
Valentina Bonito ₁ , Suzanne E Koch ₁ , Merle M Krebber ₂ , Daniel A Carvajal-Berrio _{3,

4} , Julia Marzi _{3,

4} , Renee Duijvelshoff _{1,

5} , Emily B Lurier _{1,

6} , Serena Buscone ₁ , Sylvia Dekker ₁ , Simone M J de Jong ₁ , Tristan Mes ₇ , Koen R D Vaessen ₈ , Eva M Brauchle _{3,

4} , Anton W Bosman ₇ , Katja Schenke-Layland _{3,

4} , Marianne C Verhaar ₂ , Patricia Y W Dankers ₁ , Anthal I P M Smits ₁ , Carlijn V C Bouten ₁

Affiliation

Two of the greatest challenges for successful application of small-diameter in situ tissue-engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual-functionalized with anti-thrombogenic heparin (hep) and anti-inflammatory interleukin 4 (IL-4) using a supramolecular approach. The regenerative capacity of IL-4/hep, hep-only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow-up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months). Routine analyses are augmented with Raman microspectroscopy, in order to acquire the local molecular fingerprints of the resorbing scaffold and developing tissue. Thrombosis is found not to be a confounding factor in any of the groups. Hep-only-functionalized grafts resulted in adverse tissue remodeling, with cases of local intimal hyperplasia. This is negated with the addition of IL-4, which promoted M2 macrophage polarization and more mature neotissue formation. This study shows that with bioactive functionalization, the early inflammatory response can be modulated and affect the composition of neotissue. Nevertheless, variability between graft outcomes is observed within each group, warranting further evaluation in light of clinical translation.

中文翻译：

肝素和白细胞介素 4 功能化对大鼠巨噬细胞极化和使用可吸收超分子血管移植物原位动脉组织再生的不同影响

成功应用小直径原位组织工程血管移植物的两个最大挑战是 1) 防止血栓形成和 2) 利用对移植物的炎症反应来指导功能组织再生。本研究使用超分子方法评估了电纺可吸收弹性血管移植物的体内性能，该移植物具有抗血栓形成肝素 (hep) 和抗炎白细胞介素 4 (IL-4) 双重功能。IL-4/hep、仅 hep 和裸移植物的再生能力被研究为大鼠腹主动脉中的插入移植物，并在愈合级联的关键时间点（1、3、7 天和 3 个月）进行随访）。拉曼显微光谱增强了常规分析，以获得吸收支架和发育组织的局部分子指纹。发现血栓形成不是任何组中的混杂因素。仅 Hep 功能化的移植物导致不利的组织重塑，并伴有局部内膜增生。这被添加 IL-4 所抵消，IL-4 促进了 M2 巨噬细胞极化和更成熟的新组织形成。该研究表明，通过生物活性功能化，可以调节早期炎症反应并影响新组织的组成。然而，在每组中观察到移植结果之间的差异，需要根据临床转化进行进一步评估。有局部内膜增生的病例。这被添加 IL-4 所抵消，IL-4 促进了 M2 巨噬细胞极化和更成熟的新组织形成。该研究表明，通过生物活性功能化，可以调节早期炎症反应并影响新组织的组成。然而，在每组中观察到移植结果之间的差异，需要根据临床转化进行进一步评估。有局部内膜增生的病例。这被添加 IL-4 所抵消，IL-4 促进了 M2 巨噬细胞极化和更成熟的新组织形成。该研究表明，通过生物活性功能化，可以调节早期炎症反应并影响新组织的组成。然而，在每组中观察到移植结果之间的差异，需要根据临床转化进行进一步评估。

更新日期：2021-11-04

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