Dongjiao Zhang

Mitochondria, as crucial organelles in eukaryotic cells, are deeply involved in cellular energy metabolism and biogenesis. Currently, mitochondria have been found to transfer between cells and regulate a range of cellular functions and research has found that mitochondrial transfer has been shown to play an important role in regulating bone homeostasis. Laser confocal imaging was used to confirm the occurrence of mitochondrial transfer between cells. JC-1 staining explains the state of free mitochondria in receptor cells. In order to reveal the relationship between the state and function of free mitochondria, osteogenic induction, Western blotting, flow cytometry, and in vivo experiments were conducted. RNA seq is used to analyze changes in cells. Different inhibitors were used to verify the specific mechanism of action of free mitochondrial transfer. Free mitochondrial transfer can improve the function of receptor cells through lysosomal pathway. Free mitochondria are degraded by cathepsin H (Ctsh) in lysosomes and release a large amount of cysteine after entering the receptor cells. In this process, the existence of membrane potential of free mitochondria is not critical. Cysteine, as the most important raw material for glutathione synthesis, can enhance the number and function of mitochondria in receptor cells. Our study demonstrates that free mitochondrial transfer promotes bone regeneration by increasing cysteine supply, and provides innovative insights for understanding mitochondrial transfer.

Objective: Hyperlipidemia seriously impairs titanium (Ti) implant osseointegration, and endogenous therapeutic targets remain elusive. Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) plays an important role in redox regulation and lipid metabolism. However, its role in osseointegration under hyperlipidemia conditions has not been thoroughly investigated. This study aimed to elucidate the potential role of ALDH6A1 in implant osseointegration in hyperlipidemia mice. Materials and Methods: ALDH6A1 expression levels were detected in peri‐implant tissue and in primary osteoblasts by qRT‐PCR and western blot. The role of ALDH6A1 in reducing oxidative damage and improving osseointegration on Ti implant surface was evaluated by locally overexpressing ALDH6A1 with a lentiviral vector in peri‐implant tissue in hyperlipidemia mice. Results: ALDH6A1 expression significantly decreased in hyperlipidemia mice, compared with normal mice ( p < 0.05). ALDH6A1 was downregulated in a high‐fat environment, and silencing ALDH6A1 led to osteogenic dysfunction in osteoblasts. ALDH6A1 overexpression maintained redox homeostasis and osteogenic activity of primary osteoblasts and facilitated osseointegration in hyperlipidemia mice by reducing oxidative damage in peri‐implant tissue. Conclusion: ALDH6A1 is a key protein for facilitating osseointegration by alleviating reactive oxygen species levels in hyperlipidemia, and developing specific ALDH6A1 agonists would be a promising strategy for ameliorating osseointegration in hyperlipidemia patients.

Palmitoylation is recognized as a prevalent posttranslational modification of proteins, which is highlighted in recent studies as a key player in regulating protein stability, subcellular localization, membrane transport, and other cellular biological processes. However, its role in peri-implant osteogenesis under type 2 diabetes mellitus (T2DM) remains unclear. During this study, the in vitro high-glucose model based on MC3T3-E1 cells demonstrated that a high-glucose environment in vitro markedly inhibited osteoblasts proliferation and osteogenesis; meanwhile, ZDHHC9 emerged as a significantly upregulated protein. Then, Zdhhc9 knockdown improved the dysfunction of osteoblasts and peri-implant osteogenesis of T2DM mice. In addition, co-immunoprecipitation and fluorescence co-localization analysis revealed an interaction between ZDHHC9 and cyclic guanosine monophosphate (GMP)–dependent protein kinase G 1 (PKG1), and silencing of Prkg1 prevented the improvement in osteoblasts with Zdhhc9 knockdown. Furthermore, we verified that Zdhhc9 knockdown and Prkg1 silencing altered the distance between the endoplasmic reticulum and mitochondria and the expression of mitochondria-associated endoplasmic reticulum membranes (MAMs)–related proteins in osteoblasts. Collectively, our data show that ZDHHC9 could regulate MAMs through palmitoylation of PKG1 to induce osteoblast dysfunction in T2DM. ZDHHC9 might become a novel therapeutic target for peri-implant osteogenesis in diabetes patients.

With the increase of antibiotic resistance worldwide, there is an urgent demand to develop new fungicides and approaches to address the threat to human health posed by the ineffectiveness of traditional antibiotics. In this work, an orthogonal conjugated uniform oligomer bactericide of SiPc-ddCPP was constructed between silicon phthalocyanine and porphyrin, which can effectively treat infection through photodynamic-photothermal combined therapy without considering drug resistance. Compared with organic photothermal agents induced by unstable H-aggregation with blue-shifted absorption and fluorescence/ROS quenching, this orthogonal-structured uniform SiPc-ddCPP nanoparticle shows remarkably stability and NIR photothermal effect (η = 31.15%) along with fluorescence and ROS generation. Antibacterial studies have shown that both Gram-positive and Gram-negative bacteria could be efficiently annihilated in a few minutes through synergistic PDT-PTT along with satisfactory bacterial targeting. These results suggest SiPc-ddCPP is a multifunctional NIR bactericide, which afford a new approach of synergistic PDT-PTT sterilization to conquer the crisis of antibiotic resistance.

Peri-implantitis represents an inflammatory condition characterized by the presence of plaque-related soft and hard tissue damage surrounding dental implants, often resulting in progressive alveolar bone loss and, ultimately, implant failure. Black phosphorus (BP), a novel two-dimensional (2D) material that has recently emerged in the biomedical field, has attracted increasing attention due to its unique osteogenic properties and exceptional antibacterial and antioxidant characteristics. Additionally, its outstanding biomedical attributes enhance angiogenesis and nerve regeneration. Compared to other biomaterials, its high specific surface area, high photothermal conversion efficiency, and complete biodegradability make BP a promising candidate for treating infection-related bone defects. This article reviews the biological properties of BP nanosheets (BPNSs) and discusses their potential applications in the context of peri-implantitis, aiming to provide fresh insights for future research and applications of BPNS.

Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair and regeneration. Bone tissue engineering is emerging as a promising alternative to traditional therapies like autografts and allografts. Nanobiomaterials enhance osteoblast resistance to harsh environments by promoting cell differentiation. Black phosphorus (BP), a novel 2D material in biomedicine, displays unique osteogenic and antimicrobial properties. However, BP nanosheets still face clinical limitations like rapid degradation and high‐dose cytotoxicity. To address these, the introduction of amino‐silicon phthalocyanine (SiPc‐NH₂) is investigated to see if it can enhance BP dispersion, reduce BP oxidation, and improve stability and safety for better osteogenesis and antibacterial effects through noncovalent interactions (van der Waals, π–π stacking and electrostatic interactions). Here, the self‐healing hydrogel is successfully designed using a step‐by‐step co‐assembly of BP and SiPc‐NH_2. SiPc‐NH₂ as a “structural stabilizer” of BP nanosheets reconstructed well‐dispersed BP‐SiPc‐NH₂ nanosheets, which improves the biocompatibility of BP, reduces oxidation and enhances photothermal conversion, guaranteeing osteogenic and antimicrobial properties. Furthermore, findings show BP‐SiPc‐NH₂‐induced mitochondrial changes support osteogenesis by regulating the crosstalk between Hippo and Wnt signaling pathways‐mediated mitochondrial homeostasis, and boosting cellular bioenergetics. Overall, this mitochondrial morphology‐based BP‐SiPc‐NH₂ strategy holds great promise for bone repair applications.

Purpose: Bacterial infections seriously affect the health of patients and their incidence is very high. Photothermal therapy has shown promising prospects in the treatment of bacterial infections as it can effectively kill bacteria and reduce inflammation. Black phosphorus (BP) is an emerging nanoparticle that can generate heat under the action of near-infrared light, it can safely and effectively kill bacteria through photothermal therapy. In this experiment, black phosphorus was used as a photothermal agent to kill bacteria and strontium ions were loaded onto BP to enhance its stability and antibacterial performance. Methods: BP was obtained by liquid phase exfoliation and Sr²⁺ was loaded onto the surface of BP by electrostatic interaction. Results: BP-Sr was synthesized via electrostatic interactions and characterized using various techniques. The cytocompatibility of BP-Sr was evaluated by CCK8 assay and live/dead staining which showed no significant cytotoxicity with a concentration not exceed 50 μg/mL. Meanwhile, the antibacterial effects showed 99% of bacteria died after 10 min under the action of a 2 W/cm² laser and the structure of bacteria was destroyed. Finally, the transcriptomic results suggest that bacteria death may be related to membrane destruction, metabolic disorders, and transport damage. HE staining and Gram staining also showed that inflammation was significantly alleviated after laser treatment. Conclusion: These findings propose a great solution for bacterial infection and also enrich the theoretical framework supporting the application of BP-Sr in the field of antibiosis.