Reinforced Blood-Derived Protein Hydrogels Enable Dual-Level Regulation of Bio-Physiochemical Microenvironments for Personalized Bone Regeneration with Remarkable Enhanced Efficacy

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.

Nanobiomimetic Medicine

“…Based on this point, Zhou et al have designed injectable blood‐derived protein hydrogels composed of platelet‐rich fibrin, polydopamine and SiO 2 nanofibers. [ 247 ] This protein hydrogels with high stiffness could withstand the external loading and maintain the space for bone regeneration in bone defect site. Simultaneously, the existence of stress shielding destined the upper limit of mechanical strength.…”

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

“…6,11 These autologous blood-derived protein hydrogels are prepared from the patients' own blood, which contain various instructive growth factors and have been regarded as more effective approaches for tissue repair than the exogeneous growth factors. 10 Particularly, injectable PRF (i-PRF) has emerged as a novel platelet concentrate with no additives, which is injectable before the gel formation process and has shown positive effects on bone regeneration with unique advantages. 12,13 On one hand, i-PRF with CGFs can be used in a liquid formulation, which is injectable during the gel formation period and is suitable for the filling of irregular bone defects in a minimally invasive manner.…”

“…Recently, autologous blood-derived protein hydrogels, including platelet-rich plasma, platelet-rich fibrin (PRF), and concentrated growth factors (CGF), have shown great promise in the field of regenerative medicine. − Generally, these autologous blood-derived protein hydrogels carry multiple growth factors, such as the platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), as well as insulin-like growth factor (IGF), which play crucial roles in recruiting stem cells and promoting the bone-healing process. , These autologous blood-derived protein hydrogels are prepared from the patients’ own blood, which contain various instructive growth factors and have been regarded as more effective approaches for tissue repair than the exogeneous growth factors . Particularly, injectable PRF (i-PRF) has emerged as a novel platelet concentrate with no additives, which is injectable before the gel formation process and has shown positive effects on bone regeneration with unique advantages. , On one hand, i-PRF with CGFs can be used in a liquid formulation, which is injectable during the gel formation period and is suitable for the filling of irregular bone defects in a minimally invasive manner.…”

“…That is one of the major reasons why i-PRF with insufficient immunomodulatory activity elicits unsatisfactory therapeutic outcomes on bone healing . However, to the best of our knowledge, there are only a few reports to date on the application of i-PRF hydrogels with biomechanical and biochemical microenvironment-regulating activities for bone regeneration, let alone on developing multifunctional i-PRF hydrogels with desirable immunomodulatory activity to promote M2 macrophage polarization for high-efficacy osteogenesis. , …”

“…However, the osteogenesis efficacy of i-PRF-based hydrogels is still far from satisfactory. 10,14,15 One of the key regulatory factors during the bone-repairing process is the crosstalk between the bone-forming cells and the immune cells. 16,17 Among various immune cells, macrophages are considered as the master effectors in bone regeneration by the secretion of various paracrine mediators and chemokines, as well as the recruitment of other cells to the injury site.…”