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

Abstract

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.

Balance between the CMC/ACP Nanocomplex and Blood Assimilation Orchestrates Immunomodulation of the Biomineralized Collagen Matrix

“…Therefore, it can be speculated that the blocking effect via PRF infiltration should be more significant than that of the original blood clot. In addition, the platelets within PRF can release multiple immune-related cytokines, such as tumor growth factor β, platelet-derived growth factor, and insulin-like growth factor 1, − further optimizing the immune microenvironment and promoting the regenerative process. Moreover, the surface functionalization method also showed application prospects.…”

Lyophilized Platelet-Rich Fibrin Exudate-Loaded Carboxymethyl Chitosan/GelMA Hydrogel for Efficient Bone Defect Repair

“…Then freezedried hydrogels were subjected to complete ethanol permeation through immersion in ethanol in a vacuum chamber and weighed (W 1 ). The porosity of hydrogels was calculated as (W 1 − W H )/ρV H × 100% [ρ is the density of ethanol (0.789 g/cm 3 )].…”

“…Growth factors are necessary for bone regeneration, which play vital roles in orchestrated angiogenesis and osteogenesis processes in bone healing . Recent studies have focused on the utilization of autologous growth factors from platelet concentrates for enhanced bone regeneration. − As the second generation of platelet concentrates, platelet-rich fibrin (PRF) is strictly autologous and has been frequently used as an alternative for growth factors in clinic and tissue engineering. , Several key growth factors of PRF, including the transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), can induce cell migration, proliferation, vascularization, and differentiation . According to the previous studies, PRF showed a beneficial effect on bone tissue regeneration .…”

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

“…Remarkably, these hydrogels exhibit diagnostic and therapeutic functionality for treating pathological bone defects [ 26 ]. In addition to providing structural support, the smart hydrogels implanted into bone defects also activate osteogenesis- and immune-related signaling pathways, which regulate multiple cellular behaviors in the bone microenvironment, thereby promoting bone regeneration [ 27 , 28 ].…”