I-PRF functionalized gelatin methacrylate microspheres for improving the proliferation and osteogenic differentiation of human periodontal ligament stem cells

Abstract Although human periodontal ligament stem cell (hPDLSC)-based tissue engineering have been promising for regenerating periodontal bone tissue, their effectiveness is limited by the lack of an optimal delivery vehicle for these cells. Therefore, this study reports a gelatin methacryloyl microsphere system, incorporating injectable platelet-rich fibrin and nano-hydroxyapatite (nHA) as carriers for hPDLSCs. These hybrid microspheres were effectively produced using droplet microfluidics technology, achieving a size range of 100–300 μm. Importantly, the release profile of multiple growth factors (GFs) from the microspheres was significantly extended, lasting up to 28 d. Moreover, the released GFs and nHA considerably enhanced the proliferation of encapsulated hPDLSCs along with their spreading and osteogenic differentiation. The microspheres facilitated the development of Spheroid-like cell aggregates within two weeks of culture, demonstrating a promising approach for advanced periodontal bone tissue regeneration.