Porous nanofibrous microspheres: synthesis approaches and applications to tissue regeneration

Repairing irregularly shaped tissue defects via minimally invasive approaches requires modular, injectable scaffolds capable of recapitulating the hierarchical complexity of the native extracellular matrix (ECM). While conventional solid and porous microspheres provide favorable injectability, fluidity, and space-filling capacity, they often fail to replicate the nanoscale fibrillar architecture of natural tissues, leading to suboptimal cell retention, restricted mass transport, and inadequate cell-matrix signaling. To address these limitations, porous nanofibrous microspheres (PNMs) have emerged as advanced biomimetic scaffolds that integrate microscale injectability with ECM-mimetic nanofibrous and porous architectures. This article provides an overview of PNMs synthesis approaches and applications to tissue regeneration. First, the material design criteria are examined, highlighting the integration of ECM-inspired nanofibrous topographies, interconnected porous networks, and the strategic selection of natural, synthetic, or composite polymer systems. Next, state-of-the-art fabrication strategies, including phase separation and molecular self-assembly, electrospraying, and microfluidics, are critically evaluated to elucidate how processing parameters govern microsphere size, internal morphology, and pore architecture. Finally, the article highlights recent advances in the application of PNMs for tissue regeneration. By integrating macroscopic injectability with a biomimetic architecture, PNMs offer an advanced hierarchical scaffold for the minimally invasive, targeted delivery of cells and bioactive molecules to promote tissue regeneration.