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      Black phosphorus quantum dot-modified ADSCs as a novel therapeutic for periodontitis bone loss coupling of osteogenesis and osteoimmunomodulation

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          Abstract

          Alveolar bone defect repair remains a persistent clinical challenge for periodontitis treatment. The use of peripheral functional seed cells is a hot topic in periodontitis. Herein, we explored the cellular behaviors and osteogenic ability of adipose-derived mesenchymal stem cells (ADSCs) treated with black phosphorus quantum dots (BPQDs). Additionally, macrophage polarization, osteogenic effects and angiogenesis were investigated through the paracrine pathway regulated by BPQD-modified ADSCs. Our results demonstrated that BPQDs showed good biocompatibility with ADSCs and BPQD-modified ADSCs could improve the bone repair in vivo inflammatory microenvironment by regulating osteogenesis and osteoimmunomodulation. The BPQDs increased the osteogenic differentiation of ADSCs via the Wnt/β-catenin and BMP2/SMAD5/Runx2 signaling pathway. In addition, BPQD-modified ADSCs promoted the osteogenic effect of BMSCs and facilitated the polarization of macrophages from M1 towards M2 phenotype transformation through the paracrine pathway in the periodontitis microenvironment. This strategy provides a novel idea for treatment of alveolar bone defects for periodontitis in the foreseeable future.

          Graphical abstract

          Graphic abstract. Schematic diagram of BPQDs-modified ADSCs accelerated the bone defects repair. BPQDs-modified ADSCs could boost the repair efficiency of bone defects under an inflammatory microenvironment by modulating the cross-talk between osteogenesis and osteoimmunomodulation via endogenous osteogenic differentiation and exogenous paracrine pathways.

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          Most cited references63

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          Macrophages in Tissue Repair, Regeneration, and Fibrosis.

          Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
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            Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.

            The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.
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              Periodontal diseases

              Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease. This pathophysiological situation persists through bouts of activity and quiescence, until the affected tooth is extracted or the microbial biofilm is therapeutically removed and the inflammation subsides. The severity of the periodontal disease depends on environmental and host risk factors, both modifiable (for example, smoking) and non-modifiable (for example, genetic susceptibility). Prevention is achieved with daily self-performed oral hygiene and professional removal of the microbial biofilm on a quarterly or bi-annual basis. New treatment modalities that are actively explored include antimicrobial therapy, host modulation therapy, laser therapy and tissue engineering for tissue repair and regeneration.
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                Author and article information

                Contributors
                Journal
                Mater Today Bio
                Mater Today Bio
                Materials Today Bio
                Elsevier
                2590-0064
                10 June 2024
                August 2024
                10 June 2024
                : 27
                : 101122
                Affiliations
                [a ]Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510080, China
                [b ]Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510080, China
                [c ]Zhujiang Hospital, Southern Medical University, Guangzhou, 510080, China
                Author notes
                [* ]Corresponding author. dengfl@ 123456mail.sysu.edu.cn
                [** ]Corresponding author. yudsh@ 123456mail.sysu.edu.cn
                [*** ]Corresponding author. Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510080, China. zhaowei3@ 123456mail.sysu.edu.cn
                [1]

                Note: These authors contributed equally to this work.

                Article
                S2590-0064(24)00181-9 101122
                10.1016/j.mtbio.2024.101122
                11225909
                c4133a52-7bb8-44c8-bd63-3d93c9302b18
                © 2024 The Authors

                This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

                History
                : 26 March 2024
                : 24 May 2024
                : 9 June 2024
                Categories
                Full Length Article

                black phosphorus quantum dots,adipose-derived mesenchymal stem cells,alveolar bone defect repair,osteogenesis,osteoimmunomodulation,periodontitis

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