Coupled Microfluidic Synthesis and <i>In Situ</i> RGD Functionalization of PolyHIPE Microspheres

The production of scalable and bioactive scaffolds for tissue engineering remains a significant challenge. This study presents an approach for polyHIPE microsphere preparation and in situ functionalization of the material through a microfluidic system. By coupling microfluidic particle synthesis and thiol-ene surface modifications, we demonstrate the efficient and scalable creation of monodisperse polyHIPE microspheres functionalized with RGD peptide, enhancing cell adhesion and revealing potential for three-dimensional cell culture applications as granular scaffolds. The microfluidic setup allows for real-time reaction control and uniform modification with minimal use of solvents, which is important for maintaining cell viability. The resulting microspheres were characterized using X-ray photoelectron spectroscopy, solid-state NMR, and scanning electron microscopy–energy-dispersive X-ray spectroscopy, showing that the thiol-ene reaction in the microfluidic system is highly diffusion-controlled. This work highlights the potential of large-scale production and functionalization of bioactive granular scaffolds, offering a promising approach for future applications in tissue engineering and regenerative medicine.