El-Mallah Jessica C, Ataie Zaman, Horchler Summer N, Landmesser Mary E, Asgardoon Mohammad Hossein, Waldron Olivia, Jaberi Arian, Kedzierski Alexander, Sun Mingjie, Sheikhi Amir, Ravnic Dino J
Division of Plastic Surgery, Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, 17033, USA.
Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
Angiogenesis. 2025 Sep 10;28(4):47. doi: 10.1007/s10456-025-10003-x.
Vascularization of implanted biomaterials is critical to reconstructive surgery and tissue engineering. Ultimately, the goal is to promote a rapidly perfusable hierarchical microvasculature that persists with time and can meet underlying tissue needs. We have previously shown that using a microsurgical technique, termed micropuncture (MP), in combination with porous granular hydrogel scaffolds (GHS) fabricated via interlinking hydrogel microparticles (microgels) results in a rapidly perfusable patterned microvasculature. However, whether this engineered microvasculature remains stable at longer time points remains unknown. Here, we combine MP with GHS and compare overall microvascular architecture and phenotype along with the evolving cellular landscape over a 28 day period. We demonstrate perfusable patterned microvascular stability in our MP + GHS model that occurs alongside a sustained rise in endothelial cell and macrophage recruitment. Specifically, MP yields a significant rise in M2 macrophages between the 7 and 28 day time points, suggesting ongoing microvascular remodeling, even in the presence of early pericyte stabilization. With time, the GHS microvasculature acquires a relatively equivalent arterial and venous morphology, as assessed through Ephrin-B2 and EphB4 quantification. Finally, angiography at 28 days shows that MP + GHS is associated with more perfusable microvascular loops when compared with MP + Bulk (nonporous) scaffolds. Hence, our surgically bioengineered microvasculature offers a unique opportunity to sustainably and precisely control biomaterial vascularization and ultimately advance the fields of reconstructive surgery and tissue engineering.
植入生物材料的血管化对于重建手术和组织工程至关重要。最终目标是促进一种快速可灌注的分级微血管系统，该系统能随时间持续存在并满足底层组织的需求。我们之前已经表明，使用一种称为微穿刺（MP）的显微外科技术，结合通过交联水凝胶微粒（微凝胶）制造的多孔颗粒水凝胶支架（GHS），可形成快速可灌注的有图案微血管系统。然而，这种工程化微血管系统在更长时间点是否保持稳定仍不清楚。在此，我们将MP与GHS相结合，并在28天的时间内比较整体微血管结构和表型以及不断演变的细胞景观。我们证明了在我们的MP + GHS模型中可灌注的有图案微血管的稳定性，这与内皮细胞和巨噬细胞募集的持续增加同时发生。具体而言，MP在第7天至第28天的时间点之间使M2巨噬细胞显著增加，这表明即使在早期周细胞稳定的情况下，微血管仍在持续重塑。随着时间的推移，通过Ephrin - B2和EphB4定量评估，GHS微血管获得了相对等效的动脉和静脉形态。最后，28天的血管造影显示，与MP + 块状（无孔）支架相比，MP + GHS与更多可灌注的微血管环相关。因此，我们通过手术生物工程构建的微血管系统为可持续且精确地控制生物材料血管化提供了独特机会，并最终推动重建手术和组织工程领域的发展。
