Immunomodulatory Blood-Derived Hybrid Hydrogels as Multichannel Microenvironment Modulators for Augmented Bone Regeneration

Autologous blood-derived protein hydrogels have shown great promise in the field of personalized regenerative medicine. However, the inhospitable regenerative microenvironments, especially the unfavorable immune microenvironment, are closely associated with their limited tissue-healing outcomes. Herein, novel immunomodulatory blood-derived hybrid hydrogels (PnP-iPRF) are rationally designed and constructed for enhanced bone regeneration via multichannel regulation of the osteogenic microenvironment. Such double-network hybrid hydrogels are composed of clinically approved injectable platelet-rich fibrin (i-PRF) and polycaprolactone/hydroxyapatite composite nanofibers by using enriched polydopamine (PDA) as the anchor. The polycaprolactone component in PnP-iPRF provides a reinforced structure to stimulate osteoblast differentiation in a proper biomechanical microenvironment. Most importantly, the versatile PDA component in PnP-iPRF can not only offer high adhesion capacity to the growth factors of i-PRF and create a suitable biochemical microenvironment for sustained osteogenesis but also reprogram the osteoimmune microenvironment via the induction of M2 macrophage polarization to promote bone healing. The present study will provide a new paradigm to realize enhanced osteogenic efficacy by multichannel microenvironment regulations and give new insights into engineering high-efficacy i-PRF hydrogels for regenerative medicine.