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

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.

3D printed reduced graphene oxide-GelMA hybrid hydrogel scaffolds for potential neuralized bone regeneration.

Peripheral nerves participate in bone growth and repair by secreting neurotransmitters, and enable new bone to possess physiological bone-sensing capability. However, it is difficult to achieve synchronized nerve regeneration during the healing process of large bone defects at present. As a bioactive nanomaterial, reduced graphene oxide (rGO) can promote neuronal differentiation and myelination of Schwann cells (SCs), while enhancing the adhesion and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through its strong non-covalent binding ability. In this study, 3D printing-based rGO/GelMA hydrogels with enhanced osteogenic and neurogenic dual differentiation were used to simultaneously load SCs and BMSCs. By changing the concentration of rGO(0.03%/0.05%/0.1%), the compressive strength, rheological properties and aperture of the hydrogel can be improved. In vitro, cell live/death staining, phalloidin staining and SEM showed that cells loaded on the hydrogel had a high survival rate (85%) and good adhesion ability. In vivo, we found that the rGO/GelMA hydrogel exhibited the same low inflammatory response compared to the pure-GelMA group and the cell-only group, but surrounded by collagen fibers. Meanwhile, the osteogenic and neural proteins in the rGO/GelMA group were found to be highly expressed in immunohistochemistry and immunofluorescence. In this study, a scaffold material containing double cells was used to promote synergistic regeneration of nerves and bone, providing a promising strategy for the preparation of personalized and functionalized biomimetic bone material.

Correction: Highly efficient photothermal branched Au-Ag nanoparticles containing procyanidins for synergistic antibacterial and anti-inflammatory immunotherapy.

Correction for 'Highly efficient photothermal branched Au-Ag nanoparticles containing procyanidins for synergistic antibacterial and anti-inflammatory immunotherapy' by Hanchi Wang et al., Biomater. Sci., 2023, https://doi.org/10.1039/d2bm01212j.

Highly efficient photothermal branched Au-Ag nanoparticles containing procyanidins for synergistic antibacterial and anti-inflammatory immunotherapy.

Periodontitis is an inflammatory disease caused by bacterial infection. Excessive immune response and high levels of reactive oxygen species (ROS) further lead to the irreversible destruction of surrounding tissues. Developing new antimicrobial materials that regulate the immune system to resist inflammation can effectively treat periodontal inflammation. A nanoplatform integrating Ag+, photothermal therapy (PTT), and procyanidins (PC) for precision antibacterial and synergistic immunotherapy for periodontitis was proposed. This work loaded PC into AuAg nanoparticles, and the resulting nanocomposite was named AuAg-PC. PTT can effectively remove pathogenic bacteria, but high temperatures can cause tissue damage. Ag+ contributes to the preparation of a nanoparticle branched structure that improves the photothermal efficiency and helps PTT achieve an excellent antibacterial effect and avoid periodontal tissue damage. PC regulates host immunity by eliminating intracellular ROS, inhibiting inflammatory factors, and regulating macrophage polarisation in periodontal disease sites. It enhances the host's resistance to bacterial inflammation. AuAg-PC exerted an excellent anti-inflammatory effect and promoted tissue repair in animal periodontal inflammation models. Hence, AuAg-PC significantly combats periodontal pathogens and shows great application potential in the photothermal-assisted immunotherapy of periodontitis. This design provided a new controllable and efficient treatment platform for controlling persistent inflammation infection and regulating immunity.

Facile engineering of resveratrol nanoparticles loaded with 20(S)-protopanaxadiol for the treatment of periodontitis by regulating the macrophage phenotype.

Periodontitis is an inflammatory disease, mainly caused by the formation of a subgingival plaque biofilm. In recent years, growing attention has been paid to immunotherapy in the treatment of periodontitis, and the importance of communal intervention associated with macrophage polarization was emphasized. Herein, resveratrol (RES) and 20(S)-protopanaxadiol (PPD) were successfully self-assembled into RES@PPD nanoparticles (NPs) by the phenolic resin reaction. RES@PPD NPs have good stability and biocompatibility. The combined application of PPD and RES enhances the anti-inflammatory and antioxidant properties of nanocomposites, remarkably reduces the level of reactive oxygen species, and finally realizes the coordinated regulation of host immunity in periodontitis. The detailed mechanism is as follows: RES@PPD NPs inhibit M1 polarization of macrophages, promote M2 polarization by scavenging ROS, and then inhibit the NF-κB signalling pathway to regulate host immunity. In the animal model of periodontitis, RES@PPD NPs can remarkably decrease the level of pro-inflammatory cytokines, up-regulate the anti-inflammatory cytokines, and exhibit a profound therapeutic effect on local inflammation. Therefore, RES@PPD NPs are effective in antioxidation and anti-inflammation, thus providing a promising candidate drug for the treatment of periodontitis.

Application of Bone Marrow-Derived Macrophages Combined with Bone Mesenchymal Stem Cells in Dual-Channel Three-Dimensional Bioprinting Scaffolds for Early Immune Regulation and Osteogenic Induction in Rat Calvarial Defects.

The host immune response to biomaterials is critical for determining scaffold fate and bone regeneration outcomes. Three-dimensional (3D) bioprinted scaffolds encapsulated with living cells can improve the inflammatory microenvironment and further accelerate bone repair. Here, we screened and adopted 8% methacrylamidated gelatin (GelMA)/1% methacrylamidated hyaluronic acid (HAMA) as the encapsulation system for rat bone marrow-derived macrophages (BMMs) and 3% Alginate/0.5 mg/mL graphene oxide (GO) as the encapsulation system for rat bone mesenchymal stem cells (BMSCs), thus forming a dual-channel bioprinting scaffold. The 8% GelMA/1% HAMA/3% Alginate/0.5 mg/mL GO (8/1/3/0.5) group could form a scaffold with a stable structure, good mechanical properties, and satisfied biocompatibility. When exploring the crosstalk between BMMs and BMSCs in vitro, we found that BMSCs could promote the polarization of BMMs to M2 type at the early stage, reduce the pro-inflammatory gene expression, and increase anti-inflammatory gene expression; conversely, BMMs can promote the osteogenic differentiation of BMSCs. In addition, in the model of rat calvarial defects, the dual-channel scaffold encapsulated with BMMs and BMSCs was more effective than the single-cell scaffold and the acellular scaffold. The paracrine of BMMs and BMSCs in the biodegradable dual-channel scaffold effectively promoted the M2-type polarization of macrophages in the microenvironment of early bone defects, avoided excessive inflammatory responses, and further promoted bone repair. In conclusion, our findings suggested that using 3D bioprinting to simultaneously encapsulate two primary cells of BMMs and BMSCs in a dual-channel system may be an effective way to promote bone repair from the perspective of early immune regulation and late induction of osteogenesis.

3D printing of MXene composite hydrogel scaffolds for photothermal antibacterial activity and bone regeneration in infected bone defect models.

The repair of infected bone defects with irregular shapes is still a challenge in clinical work. Infected bone defects are faced with several major concerns: the complex shapes of bone defects, intractable bacterial infection and insufficient osseointegration. To solve these problems, we developed a personalized MXene composite hydrogel scaffold GelMA/ß-TCP/sodium alginate (Sr2+)/MXene (Ti3C2) (GTAM) with photothermal antibacterial and osteogenic abilities by 3D printing. In vitro, GTAM scaffolds could kill both Gram-positive and Gram-negative bacteria by NIR irradiation due to the excellent photothermal effects of MXene. Furthermore, rat bone marrow mesenchymal stem cells were mixed into GTAM bioinks for 3D bioprinting. The cell-laden 3D printed GTAM scaffolds showed biocompatibility and bone formation ability depending on MXene, crosslinked Sr2+, and ß-TCP. In vivo, we implanted 3D printed GTAM scaffolds in S. aureus-infected mandible defects of rats with NIR irradiation. GTAM scaffolds could accelerate the healing of infection and bone regeneration, and play synergistic roles in antibacterial and osteogenic effects. This study not only provides a strategy for the precise osteogenesis of infected bone defects, but also broadens the biomedical applications of MXene photothermal materials.