The replacement of small-diameter arteries remains an unmet clinical need. Here we investigated the cellular remodeling of fibrotic conduits as vascular grafts. The formation of fibrotic conduit around subcutaneously implanted mandrels involved not only fibroblasts but also the trans-differentiation of inflammatory cells such as macrophages into fibroblastic cells, as shown by genetic lineage tracing. When fibrotic conduits were implanted as vascular grafts, the patency was low, and many fibrotic cells were found in neointima. Decellularization and anti-thrombogenic coating of fibrotic conduits produced highly patent autografts that remodeled into neoarteries, offering an effective approach to obtain autografts for clinical therapy. While autografts recruited mostly anti-inflammatory macrophages for constructive remodeling, allogenic DFCs had more T cells and pro-inflammatory macrophages and lower patency. Endothelial progenitors and endothelial migration were observed during endothelialization. Cell infiltration into DFCs was more efficient than decellularized arteries, and infiltrated cells remodeled the matrix and differentiated into smooth muscle cells (SMCs). This work provides insight into the remodeling of fibrotic conduits, autologous DFCs and allogenic DFCs, and will have broad impact on using fibrotic matrix for regenerative engineering.

小直径动脉的置换仍然是未满足的临床需求。在这里，我们研究了纤维化导管作为血管移植物的细胞重塑。如遗传谱系追踪所示，皮下植入心轴周围纤维化导管的形成不仅涉及成纤维细胞，还涉及炎症细胞（如巨噬细胞）向成纤维细胞的转分化。当纤维化导管作为血管移植物植入时，通畅性低，并且在新内膜中发现了许多纤维化细胞。纤维化导管的脱细胞和抗血栓形成涂层产生了高度开放的自体移植物，这些自体移植物可重塑为新动脉，为获得用于临床治疗的自体移植物提供了一种有效的方法。虽然自体移植物主要招募抗炎巨噬细胞进行建设性重塑，同种异体 DFC 具有更多的 T 细胞和促炎巨噬细胞，但通畅性较低。在内皮化过程中观察到内皮祖细胞和内皮迁移。细胞浸润到 DFCs 比去细胞动脉更有效，浸润细胞重塑基质并分化为平滑肌细胞 (SMCs)。这项工作提供了对纤维化导管、自体 DFC 和同种异体 DFC 重塑的深入了解，并将对使用纤维化基质进行再生工程产生广泛影响。