The regeneration of bone tissue is regulated by both osteogenic and angiogenic growth factors which are expressed in a coordinated cascade of events. The aim of this study was to create a dual growth factor-release system that allows for time-controlled release to facilitate bone regeneration. We fabricated core−shell SF/PCL/PVA nanofibrous mats using coaxial electrospinning and layer-by-layer (LBL) techniques, where bone morphogenetic protein 2 (BMP2) was incorporated into the core of the nanofibers and connective tissue growth factor (CTGF) was attached onto the surface. Our study confirmed the sustained release of BMP2 and a rapid release of CTGF. Both in vitro and in vivo experiments demonstrated improvements in bone tissue recovery with the dual-drug release system. In vivo studies showed improvement in bone regeneration by 43% compared with single BMP2 release systems. Time-controlled release enabled by the core−shell nanofiber assembly provides a promising strategy to facilitate bone healing.

Sensory neurons promote profound suppressive effects on neutrophils during Streptococcus pyogenes infection and contribute to the pathogenesis of necrotizing infection (“flesh-eating disease”). Thus, the development of new antibacterial agents for necrotizing infection is promising because of the clear streptococcal neuro-immune communication. Herein, based on the immune escape membrane exterior and competitive membrane functions of the glioma cell membrane, a novel nano neuro-immune blocker capsule was designed to prevent neuronal activation and improve neutrophil immune responses for necrotizing infection. These nano neuro-immune blockers could neutralize streptolysin S, suppress neuron pain conduction and calcitonin gene-related peptide release, and recruit neutrophils to the infection site, providing a strong therapeutic effect against necrotizing infection. Furthermore, nano neuro-immune blockers could serve as an effective inflammatory regulator and antibacterial agent via photothermal effects under near-infrared irradiation. In the Streptococcus pyogenes-induced necrotizing fasciitis mouse model, nano neuro-immune blockers showed significant therapeutic efficacy by ameliorating sensitivity to pain and promoting the antibacterial effect of neutrophils.

Immune response to implantation materials plays a critical role during early local inflammation and biomaterial-induced regeneration or restoration. A novel platelet concentrate termed i-PRF (injectable platelet-rich fibrin) has recently been developed without any additives by low centrifugation speeds. To date, scientists have investigated the capability of releasing growth factors to improve regeneration but have ignored whether i-PRF can inhibit the inflammatory effect around the wound. The present study investigated the anti-inflammation effects of i-PRF on immune response-related cells, especially macrophages and dendric cells. We found that i-PRF reduced pro-inflammatory M1 phenotype of macrophages and activated dendritic cells around muscle defect that was injected with bacterial suspension. Moreover, in vitro experiments showed similar results. i-PRF deleted inflammatory response caused by lipopolysaccharide to some extent. We determined that TLR4, an activator of inflammatory stimulation and p-p65, a key factor belongs to classical inflammatory related NF-κB signal pathway, can be inhibited by use of i-PRF. Results indicate the potential anti-inflammatory role of i-PRF during regeneration and restoration.

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Innate immune cells, especially macrophages, play a dual role in tissue repair and the defense against foreign bodies. Although biphasic calcium phosphate (BCP) ceramics have been confirmed as an excellent osteoimmunoregulatory biomaterial, it is unclear whether the ions release of BCP directly affects macrophage polarization and the mechanism by which the ions release is involved in osteoimmunomodulation. Herein, we verified the superior osteoinductive capacity of BCP in wild‐type mice and showed its inability to promote this process in macrophage‐deficient (LysM−/−) mice. Moreover, scanning electron microscopy, ion release curve, and calcein AM‐staining results confirmed that BCP‐released Ca2+ in a sustained manner, thereby maintaining the long‐term induction of M2 macrophage polarization and promoting the differentiation of mesenchymal stem cells into osteoblasts during osteogenesis. Furthermore, Ca2+ targeted the Wnt/β‐catenin signaling pathway and activated Arg1 and IL‐10 (M2 marker genes) transcription through the calcium‐sensing receptor (CaSR) in macrophages. Under treatment with a CaSR antagonist, macrophages cultured with the BCP fluid extract exhibited lower Ca2+ intake and weaker M2 macrophage polarization. These findings underscore the critical role of macrophages in bone regeneration and clarify the molecular mechanisms of Ca2+‐mediated osteoinduction by biomaterials, which is of great significance for the future design of biomaterial‐oriented tissue regeneration engineering.