Lee Donghee, Tran Huy Quang, Sharma Navatha Shree, Andrabi Syed Muntazir, Yan Zishuo, Killeen Amy C, Reinhardt Richard A, Zhu Wuqiang, Xie Jingwei
Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Small. 2025 May 2:e2502033. doi: 10.1002/smll.202502033.
Porous nanofibrous microspheres (PNMs) present a versatile and minimally invasive strategy for tissue regeneration, combining biomimetic morphology, tunable structure, and injectability. While self-assembly and co-axial electrospray are explored for PNM fabrication, these methods are limited in compositional versatility and production scalability. Here, a 3D-printed microfluidic platform is presented that enables large-scale fabrication of PNMs with precise control over size, pore architecture, and morphology. PNMs can be functionalized with bioactive molecules through UV crosslinking, enhancing their regenerative potential by promoting osteogenesis in human bone marrow stromal cells (hBMSCs), angiogenesis in human umbilical vein endothelial cells (HUVECs), and exerting anti-inflammatory effects on macrophages. Subcutaneous implantation in rats demonstrates that PNMs support cell infiltration, minimize fibrosis, and facilitate tissue integration, achieving complete cell penetration and tissue incorporation within 14 days. These findings establish PNMs as versatile, scalable, and customizable platforms, ideal for applications as injectable drugs or cell carriers, as well as powders, offering promising solutions for wound healing and tissue regeneration.
多孔纳米纤维微球（PNMs）为组织再生提供了一种多功能且微创的策略，它结合了仿生形态、可调节结构和可注射性。虽然人们探索了自组装和同轴电喷雾用于PNM制造，但这些方法在成分多样性和生产可扩展性方面存在局限性。在此，提出了一种3D打印微流控平台，该平台能够大规模制造PNMs，并对其尺寸、孔结构和形态进行精确控制。PNMs可以通过紫外线交联用生物活性分子进行功能化，通过促进人骨髓基质细胞（hBMSCs）的成骨作用、人脐静脉内皮细胞（HUVECs）的血管生成以及对巨噬细胞发挥抗炎作用来增强其再生潜力。在大鼠皮下植入表明，PNMs支持细胞浸润，使纤维化最小化，并促进组织整合，在14天内实现完全的细胞穿透和组织融合。这些发现确立了PNMs作为多功能、可扩展和可定制平台的地位，非常适合作为可注射药物或细胞载体以及粉末使用，为伤口愈合和组织再生提供了有前景的解决方案。
