3D-Printed Microfluidic Platform for Creating Porous Nanofibrous Microspheres to Regulate Cell Response and Enhance Tissue Regeneration.

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.