From the Department of Plastic Surgery, University of Virginia, Charlottesville, VA.
School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA.
Ann Plast Surg. 2022 Jun 1;88(5 Suppl 5):S466-S472. doi: 10.1097/SAP.0000000000003163. Epub 2022 Apr 23.
Acellular dermal matrix (ADM) supported implant-based reconstruction remains the most commonly performed mode of reconstruction after breast cancer. Acellular dermal matrix clinical usage has reported benefits but requires rapid and efficient vascular and cellular incorporation into the recipient to have the best outcomes. Orderly transition from M1 to M2 macrophage phenotypic profile, coordinated in part by interleukin 4 (IL-4), is an important component of vascular stabilization and remodeling. Using the ADM substrate as a delivery device for immunomodulation of macrophage phenotype holds the potential to improve integration.
Interleukin 4 was adsorbed onto ADM samples and drug elution curves were measured. Next, experimental groups of 8 C57BL/6 mice had 5-mm ADM discs surgically placed in a dorsal window chamber with a vascularized skin flap on one side and a plastic cover slip on the other in a model of implant-based breast reconstruction. Group 1 consisted of IL-4 (5 μg) adsorbed into the ADM preoperatively and group 2 consisted of an untreated ADM control. Serial gross examinations were performed with histology at day 21 for markers of vascularization, mesenchymal cell infiltration, and macrophage lineage.
Drug elution curves showed sustained IL-4 release for 10 days after adsorption. Serial gross examination showed similar rates of superficial vascular investment of the ADM beginning at the periphery by day 14 and increasing through day 21. Interleukin-4 treatment led to significantly increased CD31 staining of vascular endothelial cells within the ADM over the control group (P < 0.05) at 21 days. Although vimentin staining did not indicate a significant increase in fibroblasts overall, IL-4 did result in a significant increase in expression of α-smooth muscle actin. The expression of macrophage phenotype markers Arginase1 and iNOS present within the ADM were not significantly affected by IL-4 treatment at the day 21 time point.
Acellular dermal matrix has the potential to be used for immunomodulatory cytokine delivery during the timeframe of healing. Using implanted ADM as a delivery vehicle to drive IL-4 mediated angiogenesis and vascular remodeling significantly enhanced vascularity within the ADM substrate.
脱细胞真皮基质（ADM）支持的植入物重建仍然是乳腺癌后最常进行的重建模式。ADM 的临床应用已报告有获益，但需要快速有效地将血管和细胞纳入受体，以获得最佳效果。M1 向 M2 巨噬细胞表型的有序转变，部分由白细胞介素 4（IL-4）协调，是血管稳定和重塑的重要组成部分。使用 ADM 作为递送装置来调节巨噬细胞表型的免疫具有改善整合的潜力。
将白细胞介素 4 吸附到 ADM 样本上，并测量药物洗脱曲线。接下来，在植入物乳房重建模型中，将 8 只 C57BL/6 小鼠的实验组的 5mm ADM 圆盘通过手术放置在带有血管化皮瓣的背窗室中，一侧有 ADM，另一侧有塑料盖玻片。第 1 组为术前将白细胞介素 4（5μg）吸附到 ADM 中，第 2 组为未处理的 ADM 对照。在第 21 天进行组织学检查，以评估血管生成、间充质细胞浸润和巨噬细胞谱系的标志物。
吸附后 10 天内药物洗脱曲线显示持续释放白细胞介素 4。连续的大体检查显示，第 14 天开始，ADM 的外周开始出现类似的浅层血管投资，并在第 21 天增加。白细胞介素-4 治疗导致 ADM 内血管内皮细胞的 CD31 染色明显高于对照组（P<0.05）。尽管总体上波形蛋白染色并未表明成纤维细胞显著增加，但白细胞介素-4确实导致α-平滑肌肌动蛋白的表达显著增加。在第 21 天时间点，ADM 内的巨噬细胞表型标志物精氨酸酶 1 和诱导型一氧化氮合酶的表达并未受到白细胞介素-4 治疗的显著影响。
脱细胞真皮基质具有在愈合过程中用作免疫调节细胞因子递送的潜力。将植入的 ADM 用作递送载体，以驱动白细胞介素 4 介导的血管生成和血管重塑，可显著增加 ADM 基质内的血管生成。
