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| 1 | Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant显示文摘A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects. | Ze Lin Yuan Xiong Weilin Meng Yiqiang Hu Lili Chen Lang Chen Hang Xue Adriana CPanayi Wu Zhou Yun Sun Faqi Cao Guodong Liu Liangcong Hu Chenchen Yan Xudong Xie Chuanchuan Lin Kaiyong Cai Qian Feng Bobin Mi Guohui Liu | 2022 | Bioactive Materials2022，7，7： | 4 |
| 2 | Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold显示文摘Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA;QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects. | Hang Xue Zhenhe Zhang Ze Lin Jin Su Adriana CPanayi Yuan Xiong Liangcong Hu Yiqiang Hu Lang Chen Chenchen Yan Xudong Xie Yusheng Shi Wu Zhou Bobin Mi Guohui Liu | 2022 | Bioactive Materials2022，7，12： | 1 |
| 3 | Immunomodulatory Nanosystems:Advanced Delivery Tools for Treating Chronic Wounds显示文摘The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field. | Xiangyu Chu Yuan Xiong Samuel Knoedler Li Lu Adriana CPanayi Michael Alfertshofe Dongsheng Jiang Yuval Rinkevich Ze Lin Zhiming Zhao Guandong Daia Bobin Mi Guohui Liu | 2023 | Research2023，，4： | 0 |
| 4 | Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss显示文摘The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss. | Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu | 2024 | Signal Transduction and Targeted Therapy2024，9，2： | 0 |
| 5 | Role of the immune microenvironment in bone,cartilage,and soft tissue regeneration:from mechanism to therapeuticopportunity显示文摘Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone,cartilage,and soft tissue regeneration,effective clinical translation of these mechanisms remains a challenge.Regulation of the immune microenvironment is increasingly becoming a favorable target for bone,cartilage,and soft tissue regeneration;therefore,an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable.Herein,we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone,cartilage,and soft tissue repair and regeneration.We discuss the roles of various immune cell subsets in bone,cartilage,and soft tissue repair and regeneration processes and introduce novel strategies,for example,biomaterial-targeting of immune cell activity,aimed at regulating healing.Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone,cartilage,and soft tissue regeneration through regulation of the immune microenvironment. | Yuan Xiong Bo‑Bin Mi Ze Lin Yi‑Qiang Hu Le Yu Kang‑Kang Zha Adriana CPanayi Tao Yu Lang Chen Zhen‑Ping Liu Anish Patel Qian Feng Shuan‑Hu Zhou Guo‑Hui Liu | 2023 | Military Medical Research2023，10，4： | 0 |
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