The Role of HIF-1α in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering.

The process of repairing significant bone defects requires the recruitment of a considerable number of cells for osteogenesis-related activities, which implies the consumption of a substantial amount of oxygen and nutrients. Therefore, the limited supply of nutrients and oxygen at the defect site is a vital constraint that affects the regenerative effect, which is closely related to the degree of a well-established vascular network. Hypoxia-inducible factor (HIF-1α), which is an essential transcription factor activated in hypoxic environments, plays a vital role in vascular network construction. HIF-1α, which plays a central role in regulating cartilage and bone formation, induces vascular invasion and differentiation of osteoprogenitor cells to promote and maintain extracellular matrix production by mediating the adaptive response of cells to changes in oxygen levels. However, the application of HIF-1α in bone tissue engineering is still controversial. As such, clarifying the function of HIF-1α in regulating the bone regeneration process is one of the urgent issues that need to be addressed. This review provides insight into the mechanisms of HIF-1α action in bone regeneration and related recent advances. It also describes current strategies for applying hypoxia induction and hypoxia mimicry in bone tissue engineering, providing theoretical support for the use of HIF-1α in establishing a novel and feasible bone repair strategy in clinical settings.

Glucose-Responsive Self-Healing Bilayer Drug Microneedles Promote Diabetic Wound Healing Via a Trojan-Horse Strategy.

Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.

Case report and literature review: autonomous robotic system assisted palatal implantation at an anterior teeth site compromised by periapical cyst.

Background: Immediate implant placement (IIP), which preserves gingival height and papilla shape while simultaneously accelerating the implant treatment period, has become a popular method due to its commendable clinical outcomes. Nonetheless, deploying immediate implants demands specific preconditions concerning the remaining alveolar bone. This poses a challenge to the accuracy of implant surgery. Case presentation: In this report, we present the case of a 60-year-old woman with a left upper anterior tooth crown dislodged for over a month. Cone beam computed tomography (CBCT) revealed the absence of a labial bone wall on tooth 22, a remaining 1 mm bone wall on the labial side of the root apex, and a 17.2 mm*8.9 mm*4.7 mm shadow in the periapical region of the root apices of teeth 21 and 22, with the narrowest width on the sagittal plane being approximately 5 mm. After the surgeon removed the cyst, they completed the subsequent implantation surgery using an autonomous robot in a challenging aesthetic area. This method circumvented the potential exposure of the screw thread on the labial implant surface, assured initial implant stability. Conclusion: Five months after the operation, the dental crown was restored. The implant remained stable, with yielding notable clinical results. To the best of our knowledge, this clinical case is the first to report the feasibility and precision of immediate implantation in anterior teeth site with periapical cyst removal, performed by an autonomous robotic surgical system. Autonomous robots exhibit exceptional accuracy by accurately controlling axial and angular errors. It can improve the accuracy of implant surgery, which may become a key technology for changing implant surgery. However, further clinical trials are still needed to provide a basis for the rapid development of robotic surgery field.

NF-κB-Signaling-Targeted Immunomodulatory Nanoparticle with Photothermal and Quorum-Sensing Inhibition Effects for Efficient Healing of Biofilm-Infected Wounds.

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.

Black Phosphorus - A Rising Star in the Antibacterial Materials.

Antibiotics are the most commonly used means to treat bacterial infection at present, but the unreasonable use of antibiotics induces the generation of drug-resistant bacteria, which causes great problems for their clinical application. In recent years, researchers have found that nanomaterials with high specific surface area, special structure, photocatalytic activity and other properties show great potential in bacterial infection control. Among them, black phosphorus (BP), a two-dimensional (2D) nanomaterial, has been widely reported in the treatment of tumor and bone defect due to its excellent biocompatibility and degradability. However, the current theory about the antibacterial properties of BP is still insufficient, and the relevant mechanism of action needs to be further studied. In this paper, we introduced the structure and properties of BP, elaborated the mechanism of BP in bacterial infection, and systematically reviewed the application of BP composite materials in the field of antibacterial. At the same time, we also discussed the challenges faced by the current research and application of BP, which laid a solid theoretical foundation for the further study of BP in the future.

Novel PVAMA/GelMA aerogels prepared by liquid-phase collection of photoinitiated polymerisation: injectable and flowable low-density 3D scaffolds for bone regeneration.

Nanofibrous scaffolds, which are morphologically/structurally similar to native extracellular matrix, are ideal biomaterials for tissue engineering and regenerative medicine. However, the use of traditional electrospinning techniques to produce three-dimensional (3D) nanofibrous scaffolds with desired structural properties presents difficulty. To address this challenge, we prepared a novel liquid-phase-collected photoinitiated polymerised aerogel 3D scaffold (LPPI-AG) using the thermally induced (nanofiber) self-aggregation method after liquid-phase electrospinning of the hydroxyapatite-doped methacrylated polyvinyl alcohol/methacrylated gelatine solution obtained by photoinitiated polymerisation. The fabricated aerogel scaffolds had a high porosity of approximately 99.01% ± 0.40% and an interconnected network structure with pore sizes ranging from submicron to ∼300 µm. The new aerogel rapidly became flowable when exposed to a solution, and it can fill gaps and repair gap edges effectively and be loaded with nutrients and growth factors that promote bone growth for bone tissue engineering. LPPI-AG scaffolds can considerably promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo studies showed that the LPPI-AG scaffold significantly promoted bone formation in a mouse model of critical-size calvarial defects.