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.

Advances of Schwann cells in peripheral nerve regeneration: From mechanism to cell therapy.

Peripheral nerve injuries (PNIs) frequently occur due to various factors, including mechanical trauma such as accidents or tool-related incidents, as well as complications arising from diseases like tumor resection. These injuries frequently result in persistent numbness, impaired motor and sensory functions, neuropathic pain, or even paralysis, which can impose a significant financial burden on patients due to outcomes that often fall short of expectations. The most frequently employed clinical treatment for PNIs involves either direct sutures of the severed ends or bridging the proximal and distal stumps using autologous nerve grafts. However, autologous nerve transplantation may result in sensory and motor functional loss at the donor site, as well as neuroma formation and scarring. Transplantation of Schwann cells/Schwann cell-like cells has emerged as a promising cellular therapy to reconstruct the microenvironment and facilitate peripheral nerve regeneration. In this review, we summarize the role of Schwann cells and recent advances in Schwann cell therapy in peripheral nerve regeneration. We summarize current techniques used in cell therapy, including cell injection, 3D-printed scaffolds for cell delivery, cell encapsulation techniques, as well as the cell types employed in experiments, experimental models, and research findings. At the end of the paper, we summarize the challenges and advantages of various cells (including ESCs, iPSCs, and BMSCs) in clinical cell therapy. Our goal is to provide the theoretical and experimental basis for future treatments targeting peripheral nerves, highlighting the potential of cell therapy and tissue engineering as invaluable resources for promoting nerve regeneration.

Mild Thermotherapy-Assisted GelMA/HA/MPDA@Roxadustat 3D-Printed Scaffolds with Combined Angiogenesis-Osteogenesis Functions for Bone Regeneration.

Early reconstruction of the vascular network is a prerequisite to the effective treatment of substantial bone defects. Traditional 3D printed tissue engineering scaffolds designed to repair large bone defects do not effectively regenerate the vascular network, and rely only on the porous structure within the scaffold for nutrient transfer and metabolic waste removal. This leads to delayed bone restoration and hence functional recovery. Therefore, strategies for generation scaffolds with the capacity to efficiently regenerate vascularization should be developed. This study loads roxarestat (RD), which can stabilize HIF-1α expression in a normoxic environment, onto the mesopore polydopamine nanoparticles (MPDA@RD) to enhance the reconstruction of vascular network in large bone defects. Subsequently, MPDA@RD is mixed with GelMA/HA hydrogel bioink to fabricate a multifunctional hydrogel scaffold (GHM@RD) through 3D printing. In vitro results show that the GHM@RD scaffolds achieve good angiogenic-osteogenic coupling by activating the PI3K/AKT/HSP90 pathway in BMSCs and the PI3K/AKT/HIF-1α pathway in HUVECs under mild thermotherapy. In vivo experiments reveal that RD and mild hyperthermia synergistically induce early vascularization and bone regeneration of critical bone defects. In conclusion, the designed GHM@RD drug delivery scaffold with mild hyperthermia holds great therapeutic value for future treatment of large bone defects.

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.

Platelet-rich fibrin as an autologous biomaterial for bone regeneration: mechanisms, applications, optimization.

Platelet-rich fibrin, a classical autologous-derived bioactive material, consists of a fibrin scaffold and its internal loading of growth factors, platelets, and leukocytes, with the gradual degradation of the fibrin scaffold and the slow release of physiological doses of growth factors. PRF promotes vascular regeneration, promotes the proliferation and migration of osteoblast-related cells such as mesenchymal cells, osteoblasts, and osteoclasts while having certain immunomodulatory and anti-bacterial effects. PRF has excellent osteogenic potential and has been widely used in the field of bone tissue engineering and dentistry. However, there are still some limitations of PRF, and the improvement of its biological properties is one of the most important issues to be solved. Therefore, it is often combined with bone tissue engineering scaffolds to enhance its mechanical properties and delay its degradation. In this paper, we present a systematic review of the development of platelet-rich derivatives, the structure and biological properties of PRF, osteogenic mechanisms, applications, and optimization to broaden their clinical applications and provide guidance for their clinical translation.

A Hemoglobin Bionics-Based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation.

Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, it is aimed to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" is synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and is delivered via a glucose/pH-responsive microneedle bandage (PDGa@GMB). The PDGa@GMB downregulates the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrates insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (>90%) against resistant strains of both S. aureus and E. coli, and accelerates tissue recovery (<20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity.

Finite Element Analysis of Different Carbon Fiber Reinforced Polyetheretherketone Dental Implants in Implant-supported Fixed Denture.

OBJECTIVES: The purpose of this study is to determine the feasibility of polyetheretherketone-based dental implants, and analyze the stress and strain around different kinds of dental implants by finite element analysis. METHODS: The radiographic data was disposed to models in Mimics 19.0. 3D models of implants, crowns and jawbones were established and combined in SolidWorks 2018. Appling axial and oblique loads of 100 N, cloud pictures were exported in Ansys Workbench 18.0 to calculate and analyze the stress and strain in and around different implants. RESULTS: Oblique load tended to deliver more stress to bone tissue than axial load. The uniformity of stress distribution was the best for 30% short carbon fiber reinforced polyetheretherketone implants at axial and buccolingual directions. Stress shielding phenomenon occurred at the neck of 60% continuous carbon fiber reinforced polyetheretherketone and titanium implants. Stress concentration appeared in PEEK implants and the load of bone tissue would aggravate. CONCLUSIONS: 30% short carbon fiber reinforced polyetheretherketone implants demonstrate a more uniform stress distribution in bone-implant contact and surrounding bone than titanium. Stress shielding and stress concentration may be avoided in bone-implant interface and bone tissue. Bone disuse-atrophy may be inhibited in PEEK-based implants.

The Application of Drugs and Nano-Therapies Targeting Immune Cells in Hypoxic Inflammation.

Immune cells are pivotal in the dynamic interplay between hypoxia and inflammation. During hypoxic conditions, HIF-1α, a crucial transcription factor, facilitates the adaptation of immune cells to the hypoxic micro-environment. This adaptation includes regulating immune cell metabolism, significantly impacting inflammation development. Strategies for anti-inflammatory and hypoxic relief have been proposed, aiming to disrupt the hypoxia-inflammation nexus. Research extensively focuses on anti-inflammatory agents and materials that target immune cells. These primarily mitigate hypoxic inflammation by encouraging M2-macrophage polarization, restraining neutrophil proliferation and infiltration, and maintaining Treg/TH17 balance. Additionally, oxygen-releasing nano-materials play a significant role. By alleviating hypoxia and clearing reactive oxygen species (ROS), these nano-materials indirectly influence immune cell functions. This paper delves into the response of immune cells under hypoxic conditions and the resultant effects on inflammation. It provides a comprehensive overview of various therapies targeting specific immune cells for anti-inflammatory purposes and explores nano-materials that either carry or generate oxygen to alleviate anoxic micro-environments.

Effects of H2O on Improving the Performance of a Solid Composite Electrolyte Fabricated via an Air-Processable Technique.

Inert atmosphere is normally necessary for fabrication of solid composite electrolytes (SCEs) as a crucial part of solid-state Li-metal batteries in order to avoid undesirable reactions induced by ambient moisture. Herein, we developed an air-processable technique to fabricate SCEs by employing LiCF3SO3 (LiOTf) as the Li salt, which was combined with Li6.4La3Zr1.4Ta0.6O12 (LLZTO) as the fast Li-conductor and polyvinylidene difluoroethylene/polyvinyl acetate (PVDF/PVAC) as the polymer matrix. With the assistance of trace H2O dissolved in electrolyte solution, the room-temperature Li+ conductivity of the obtained aSCE reached as high as 5.09 × 10-4 S cm-1, which was over 3 orders of magnitude higher than that of the one (iSCE, 1.93 × 10-7 S cm-1) cast by the electrolyte solution prepared in an inert atmosphere. The theoretical calculation results reveal that the oxygen atom of H2O exhibits a high propensity to interact with the Li atom in LiOTf (Li···O), thereby establishing a hydrogen bond with the oxygen atom (H···O) in N,N-dimethylformamide (solvent). Such interactions promoted the dissociation of LiOTf and led to the formation of uniform Li+ transportation channels. Simultaneously, the composition distribution was also altered, resulting in a smoother surface of aSCE and lowered crystallinity of PVDF. On this basis, the LiOTf/LLZTO/PVDF/PVAC solution at 60 °C was directly coated onto the surface of the LiFePO4 (LFP) cathode to fabricate the LFP-aSCE film after drying in an oven. The assembled LFP-aSCE/Li battery wetted by trace sulfolane exhibited an initial Coulombic efficiency of 94.7% and a capacity retention rate of up to 96% at 0.2 C (137 mAh g-1) after 180 cycles and a high capacity of 143.7 mAh g-1 at 0.5 C (150 cycles). Overall, this work could pave the way for the facile fabrication of solid electrolytes.

Isolation, identification and osteogenic capability analysis of mesenchymal stem cells derived from different layers of human maxillary sinus membrane.

AIM: To discover the populations of mesenchymal stem cells (MSCs) derived from different layers of human maxillary sinus membrane (hMSM) and evaluate their osteogenic capability. MATERIALS AND METHODS: hMSM was isolated into a monolayer using the combined method of physical separation and enzymatic digestion. The localization of MSCs in hMSM was performed by immunohistological staining and other techniques. Lamina propria layer-derived MSCs (LMSCs) and periosteum layer-derived MSCs (PMSCs) from hMSM were expanded using the explant cell culture method and identified by multilineage differentiation assays, colony formation assay, flow cytometry and so on. The biological characteristics of LMSCs and PMSCs were compared using RNA sequencing, reverse transcription and quantitative polymerase chain reaction, immunofluorescence staining, transwell assay, western blotting and so forth. RESULTS: LMSCs and PMSCs from hMSMs were both CD73-, CD90- and CD105-positive, and CD34-, CD45- and HLA-DR-negative. LMSCs and PMSCs were identified as CD171+/CD90+ and CD171-/CD90+, respectively. LMSCs displayed stronger proliferation capability than PMSCs, and PMSCs presented stronger osteogenic differentiation capability than LMSCs. Moreover, PMSCs could recruit and promote osteogenic differentiation of LMSCs. CONCLUSIONS: This study identified and isolated two different types of MSCs from hMSMs. Both MSCs served as good potential candidates for bone regeneration.

Synthetic IMU Datasets and Protocols Can Simplify Fall Detection Experiments and Optimize Sensor Configuration.

Falls represent a significant cause of injury among the elderly population. Extensive research has been devoted to the utilization of wearable IMU sensors in conjunction with machine learning techniques for fall detection. To address the challenge of acquiring costly training data, this paper presents a novel method that generates a substantial volume of synthetic IMU data with minimal actual fall experiments. First, unmarked 3D motion capture technology is employed to reconstruct human movements. Subsequently, utilizing the biomechanical simulation platform Opensim and forward kinematic methods, an ample amount of training data from various body segments can be custom generated. Synthetic IMU data was then used to train a machine learning model, achieving testing accuracies of 91.99% and 86.62% on two distinct datasets of actual fall-related IMU data. Building upon the simulation framework, this paper further optimized the single IMU attachment position and multiple IMU combinations on fall detection. The proposed method simplifies fall detection data acquisition experiments, provides novel venue for generating low cost synthetic data in scenario where acquiring data for machine learning is challenging and paves the way for customizing machine learning configurations.

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.

New strategy of personalized tissue regeneration: when autologous platelet concentrates encounter biomaterials.

Components in blood play an important role in wound healing and subsequent tissue regeneration processes. The fibrin matrix and various bioactive molecules work together to participate in this complex yet vital biological process. As a means of personalized medicine, autologous platelet concentrates have become an integral part of various tissue regeneration strategies. Here, we focus on how autologous platelet concentrates play a role in each stage of tissue healing, as well as how they work in conjunction with different types of biomaterials to participate in this process. In particular, we highlight the use of various biomaterials to protect, deliver and enhance these libraries of biomolecules, thereby overcoming the inherent disadvantages of autologous platelet concentrates and enabling them to function better in tissue regeneration.

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.

Culture-Delivery Live Probiotics Dressing for Accelerated Infected Wound Healing.

Probiotic therapy in infected wound healing is hindered by its low viability and colonization efficiency during treatments. Developing dressings that maintain metabolic activity and prevent the potential leakage of probiotics is imperative. Herein, a culture-delivery live probiotics hydrogel dressing is designed and synthesized, formed by gelatin modified with norbornene (GelNB) and sulfhydryl (GelSH), distributing Lactobacillus reuteri (L. reuteri)-laden alginate microspheres (AlgMPs). GelNB-GelSH hydrogel (GelNBSH) incorporating AlgMPs embedding L. reuteri (GelNBSH-L) possesses bioprintability and efficient polymerization that can maintain the activity of L. reuteri in situ, promote its proliferation, and limit its leakage. Thereby, GelNBSH-L achieved a sustainable antimicrobial effect against both S. aureus and E. coli (>90%). Above all, the results show that GelNBSH-L could ensure propitious viability and efficient antibacterial properties of probiotics, effectively inhibit the further development of bacterial infectious wounds and shorten the repair cycle, aiding in ameliorating future clinical probiotic biotherapy.

Amplification of oxidative damage using near-infrared II-mediated photothermal/thermocatalytic effects for periodontitis treatment.

Periodontitis is a biofilm-related disease characterized by damage to the periodontal tissue and the development of systemic diseases. However, treatment of periodontitis remains unsatisfactory, especially with deep-tissue infections. This study describes rationally designed multifunctional photothermocatalytic agents for near-infrared-II light-mediated synergistic antibiofilm treatment, through modification of Lu-Bi2Te3 with Fe3O4 and poly(ethylene glycol)-b-poly(l-arginine) (PEG-b-PArg). Notably, 1064-nm laser irradiation led to photothermal/thermocatalytic effects, resulting in the synergistic generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and consequent damage to the biofilm. This treatment was based on the thermoelectric and photothermal conversion properties of Lu-Bi2Te3, the peroxidase-like catalytic capacity of Fe3O4, and the guanidinium polymer, PEG-b-PArg. Oxidative damage to biofilm was further enhanced by H2O2, resulting in the effective elimination of biofilm both in vitro and in vivo. These findings suggest that this synergistic therapeutic strategy is effective for the clinical treatment of periodontitis. STATEMENT OF SIGNIFICANCE: The current treatment for periodontitis involves time-consuming and labor-intensive clinical scaling of the teeth. The present study is the first to assess the efficacy of a photothermal catalyst for periodontitis treatment. This used near-infrared-II light at 1064 nm to induce oxidative damage in the biofilm, resulting in its degradation. The synergistic photothermal/thermoelectric effect produced deep tissue penetration and was well tolerated, and can kill the biofilm formed by periodontitis pathogens up to 5 orders of magnitude, effectively treating the biofilm-induced periodontitis.

Egg white-derived peptide KPHAEVVLR promotes wound healing in rat palatal mucosa via PI3K/AKT/mTOR pathway.

KPHAEVVLR (KR-9) is a peptide derived from egg white hydrolyzed, which has been found to accelerate skin wound healing in mice. However, the effect of KR-9 on wound healing on palatal mucosa in rats remains unknown, and the mechanism through which KR-9 promotes wound healing should be further explored. Herein, we aimed to investigate the effect and mechanism of KR-9 peptide on palatal mucosa wound healing. Our results showed that KR-9 reduced the wound area of palatal mucosa in rats and promoted human gingival fibroblasts(HGFs) migration and proliferation.The peptide can enter into cytoplasm. It also increased the phosphorylation of PI3K, AKT, and mTOR protein. The effect of KR-9 on HGFs migration and proliferation could be reversed by PI3K inhibitor. These results demonstrated that KR-9 peptide facilitated wound healing of palatal mucosa in rats by promoting HGFs migration and proliferation, which was mediated by PI3K/AKT/mTOR signaling pathway. This data proves that KR-9 might be used as a potential agent for wound healing treatment.

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.

N-Acetyl-l-cysteine-Derived Carbonized Polymer Dots with ROS Scavenging via Keap1-Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis.

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N-acetyl-l-cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H2 O2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.

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.