Interleukin-1 and estrogen protect against disseminating dentoalveolar infections

Dentoalveolar bacterial infections cause localized tissue and bone destruction, but usually remain well-localized within teeth in immunocompetent hosts. However, in certain cases these infections may invade head and neck tissues, resulting in orofacial abscesses, cellulitis and sepsis, with resultant high morbidity and even mortality. In the present studies, we developed a novel model of spreading dentoalveolar infections in mice by treatment with neutralizing antibodies against both interleukin-la （IL-1a） and IL-1β. Surprisingly male but not female mice given anti-lL-1 antibodies developed orofacial abscesses, weight loss, splenomegaly and sepsis. Female mice developed abscesses and sepsis comparable to males following ovariectomy （OVX）, which was reversed by estrogen supplementation. Anti-lL-1 blockade inhibited IL-12, interferon y （IFNy） and IL-6 but not IL-IO expression in infrabony lesions, suggestive of a local anti-inflammatory response. There was greater infiltration of neutrophils and other inflammatory ceils into lesions in anti-lL-l-treated animals; however, blood leukocytes had reduced bacterial phagocytic and killing activity ex vivo. Estrogen directly stimulated IL-1 production by macrophages, suggesting that the resistance of females to disseminating dentoalveolar infections may be due to their heightened pro-inflammatory responses following bacterial challenge, leading to enhanced localization of these infections.

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal rnechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma （PRP） therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and （pre-）clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of iniured peripheral nerves around dental implants is discussed.

Tailoring the multiscale mechanics of tunable decellularized extracellular matrix (dECM) for wound healing through immunomodulation

With the discovery of the pivotal role of macrophages in tissue regeneration through shaping the tissue immune microenvironment, various immunomodulatory strategies have been proposed to modify traditional biomaterials. Decellularized extracellular matrix (dECM) has been extensively used in the clinical treatment of tissue injury due to its favorable biocompatibility and similarity to the native tissue environment. However, most reported decellularization protocols may cause damage to the native structure of dECM, which undermines its inherent advantages and potential clinical applications. Here, we introduce a mechanically tunable dECM prepared by optimizing the freeze-thaw cycles. We demonstrated that the alteration in micromechanical properties of dECM resulting from the cyclic freeze-thaw process contributes to distinct macrophage-mediated host immune responses to the materials, which are recently recognized to play a pivotal role in determining the outcome of tissue regeneration. Our sequencing data further revealed that the immunomodulatory effect of dECM was induced via the mechnotrasduction pathways in macrophages. Next, we tested the dECM in a rat skin injury model and found an enhanced micromechanical property of dECM achieved with three freeze-thaw cycles significantly promoted the M2 polarization of macrophages, leading to superior wound healing. These findings suggest that the immunomodulatory property of dECM can be efficiently manipulated by tailoring its inherent micromechanical properties during the decellularization process. Therefore, our mechanics-immunomodulation-based strategy provides new insights into the development of advanced biomaterials for wound healing.

A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis

Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

Enhancement of critical-sized bone defect regeneration by magnesium oxide-reinforced 3D scaffold with improved osteogenic and angiogenic properties

The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic medicine.In recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may build.Here,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD repairing.The composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure PCL.The in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week implantation.Overall,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.

Mechanical and biological properties of Ti–(0–25 wt%)Nb alloys for biomedical implants application

Binary titanium–niobium(Ti–Nb)alloys have recently been attracted due to low Young’s moduli and non-toxic properties.This study explores the influence of low Nb content(0–25 wt%)on the comprehensive parameters of tensile stress–strain relationships(ultimate strength(rUTS),yield strength(r0.2)and elastic modulus(E)),surfaces properties(Vickers microhardness,surface roughness(Ra),water contact angle(WCA),X-ray diffraction(XRD)and scanning electron microscopy(SEM)),corrosion resistance(in artificial saliva and lactic acid)and biological properties(cytotoxicity and alkaline phosphatase activity of MC3T3-E1 pre-osteoblasts)of Ti–xNb alloys(x紏5,10,15,20 and 25 wt%),with using commercially pure grade 2 titanium(cp-Ti)as control.XRD results shown that all the Ti–xNb alloys comprised atb Ti alloy phases,such that the b phase increased correspondingly with the increased amount of Nb in the alloy,as well as the reduction of E(69–87 GPa).Except Ti–5Nb,all other Ti–xNb alloys showed a significantly higher hardness,increased rUTS and r0.2,and decreased WCA compared with cp-Ti.No corrosion was detected on Ti–xNb alloys and cp-Ti in artificial saliva and lactic acid solutions.The cytotoxicity of Ti–xNb alloys was comparable to that of cp-Ti in MC3T3-E1 pre-osteoblasts without interference from differentiation behaviour,but the proliferation rate of the Ti–5Nb alloy was lower than other groups.In overall,binary Ti–(10–25 wt%)Nb alloys are promising candidate for orthopaedic and dental implants due to their improved mechanical properties and comparable biological performance,while Ti–5Nb should be used with caution.