Reinforced Blood-Derived Protein Hydrogels Enable Dual-Level Regulation of Bio-Physiochemical Microenvironments for Personalized Bone Regeneration with Remarkable Enhanced Efficacy
Sicong Ren, Xiaoduo Tang, Lijun Liu, Fanrong Meng, Xudong Yang, Nuo Li, Zhiying Zhang, Maierhaba Aimaijiang, Manxuan Liu, Xinchen Liu, Hanchi Wang, Hanchi Wang, Huimin Huangfu, Huan Wang, Huan Wang, Junhu Zhang, Daowei Li, Yanmin Zhou
Abstract
Physiological microenvironment engineering has shown great promise in combating a variety of diseases. Herein, we present the rational design of reinforced and injectable blood-derived protein hydrogels (PDA@SiO2-PRF) composed of platelet-rich fibrin (PRF), polydopamine (PDA), and SiO2 nanofibers that can act as dual-level regulators to engineer the microenvironment for personalized bone regeneration with high efficacy. From the biophysical level, PDA@SiO2-PRF with high stiffness can withstand the external loading and maintaining the space for bone regeneration in bone defects. Particularly, the reinforced structure of PDA@SiO2-PRF provides bone extracellular matrix (ECM)-like functions to stimulate osteoblast differentiation via Yes-associated protein (YAP) signaling pathway. From the biochemical level, the PDA component in PDA@SiO2-PRF hinders the fast degradation of PRF to release autologous growth factors in a sustained manner, providing sustained osteogenesis capacity. Overall, the present study offers a dual-level strategy for personalized bone regeneration by engineering the biophysiochemical microenvironment to realize enhanced osteogenesis efficacy.