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| 1 | Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis显示文摘The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism.In this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment.Particularly,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional performance.The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres.In addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA.In summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA. | Ying Han Jielai Yang Weiwei Zhao Haimang Wang Yulong Sun Yuji Chen Jing Luo Lianfu Deng Xiangyang Xu Wenguo Cui Hongyu Zhang | 2021 | Bioactive Materials2021，6，10： | 8 |
| 2 | Hydration-Enhanced Lubricating Electrospun Nanofibrous Membranes Prevent Tissue Adhesion显示文摘Lubrication is the key to efficient function of human tissues and has significant impact on the comfort level.However,the construction of a lubricating nanofibrous membrane has not been reported as yet,especially using a one-step surface modification method.Here,bioinspired by the superlubrication mechanism of articular cartilage,we successfully construct hydration-enhanced lubricating nanofibers via one-step in situ grafting of a copolymer synthesized by dopamine methacrylamide(DMA)and 2-methacryloyloxyethyl phosphorylcholine(MPC)onto electrospun polycaprolactone(PCL)nanofibers.The zwitterionic MPC structure provides the nanofiber surface with hydration lubrication behavior.The coefficient of friction(COF)of the lubricating nanofibrous membrane decreases significantly and is approximately 65%less than that of pure PCL nanofibers,which are easily worn out under friction regardless of hydration.The lubricating nanofibers,however,show favorable wear-resistance performance.Besides,they possess a strong antiadhesion ability of fibroblasts compared with pure PCL nanofibers.The cell density decreases approximately 9-fold,and the cell area decreases approximately 12 times on day 7.Furthermore,the in vivo antitendon adhesion data reveals that the lubricating nanofiber group has a significantly lower adhesion score and a better antitissue adhesion.Altogether,our developed hydration-enhanced lubricating nanofibers show promising applications in the biomedical field such as antiadhesive membranes. | Liang Cheng Yi Wang Guoming Sun Shizhu Wen Lianfu Deng Hongyu Zhang Wenguo Cui | 2020 | Research2020，，1： | 6 |
| 3 | Black phosphorus-based 2D materials for bone therapy显示文摘Since their discovery,Black Phosphorus(BP)-based nanomaterials have received extensive attentions in the fields of electromechanics,optics and biomedicine,due to their remarkable properties and excellent biocompatibility.The most essential feature of BP is that it is composed of a single phosphorus element,which has a high degree of homology with the inorganic components of natural bone,therefore it has a full advantage in the treatment of bone defects.This review will first introduce the source,physicochemical properties,and degradation products of BP,then introduce the remodeling process of bone,and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels,polymer membranes,microspheres,and three-dimensional(3D)printed scaffolds.Finally,we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application. | Liang Cheng Zhengwei Cai Jingwen Zhao Fei Wang Min Lu Lianfu Deng Wenguo Cui | 2020 | Bioactive Materials2020，5，4： | 4 |
| 4 | Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair显示文摘In the field of bone defect repair,3D printed scaffolds have the characteristics of personalized customization and accurate internal structure.However,how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after transplantation.Herein,inspired by the unique biological structure of“lotus seedpod”,hydrogel microspheres encapsulating deferoxamine(DFO)liposomes were prepared through microfluidic technology as“lotus seeds”,and skillfully combined with a three-dimensional(3D)printed bioceramic scaffold with biomimetic“lotus”biological structure which can internally grow blood vessels.In this composite scaffold system,DFO was effectively released by 36%in the first 6 h,which was conducive to promote the growth of blood vessels inside the scaffold quickly.In the following 7 days,the release rate of DFO reached 69%,which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells(BMSCs).It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells(HUVECs)to form the vascular morphology within 6 h in vitro.In vivo,the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α,CD31,OPN,and OCN in the rat femoral defect model,significantly cutting down the time of bone repair.To sum up,this“lotus seedpod”inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future. | Xiaoyu Han Mingjie Sun Bo Chen Qimanguli Saiding Junyue Zhang Hongliang Song Lianfu Deng Peng Wang Weiming Gong Wenguo Cui | 2021 | Bioactive Materials2021，6，6： | 4 |
| 5 | Fullerol-hydrogel microfluidic spheres for in situ redox regulation of stem cell fate and refractory bone healing显示文摘The balance of redox homeostasis is key to stem cell maintenance and differentiation.However,this balance is disrupted by the overproduced reactive oxygen species(ROS)in pathological conditions,which seriously impair the therapeutic efficacy of stem cells.In the present study,highly dispersed fullerol nanocrystals with enhanced bioreactivity were incorporated into hydrogel microspheres using one-step innovative microfluidic technology to construct fullerol-hydrogel microfluidic spheres(FMSs)for in situ regulating the redox homeostasis of stem cells and promoting refractory bone healing.It was demonstrated that FMSs exhibited excellent antioxidant activity to quench both intracellular and extracellular ROS,sparing stem cells from oxidative stress damage.Furthermore,these could effectively promote the osteogenic differentiation of stem cells with the activation of FoxO1 signaling,indicating the intrinsically osteogenic property of FMSs.By injecting the stem cells-laden FMSs into rat calvarial defects,the formation of new bone was remarkably reinforced,which is a positive synergic effect from modulating the ROS microenvironment and enhancing the osteogenesis of stem cells.Collectively,the antioxidative FMSs,as injectable stem cell carriers,hold enormous promise for refractory bone healing,which can also be expanded to deliver a variety of other cells,targeting diseases that require in situ redox regulation. | Jielai Yang Jing Liang Yuan Zhu Mu Hu Lianfu Deng Wenguo Cui Xiangyang Xu | 2021 | Bioactive Materials2021，6，12： | 3 |
| 6 | Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue显示文摘Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior.However,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes.Here,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue remodeling.This bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors.Besides,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal pathway.Furthermore,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone. | Zhengwei Cai Qimanguli Saiding Liang Cheng Liucheng Zhang Zhen Wang Fei Wang Xinliang Chen Gang Chen Lianfu Deng Wenguo Cui | 2021 | Bioactive Materials2021，6，12： | 2 |
| 7 | Promotion of neurite outgrowth and protective effect of erythropoietin on the retinal neurons of rats显示文摘 | ZHONG Yisheng YAO Huiping DENG Lianfu | 2007 | Graefes Arch Clin Exp Ophthalmol2007，245，12： | 1 |
| 8 | Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release显示文摘The occurrence of osteoarthritis is closely related to progressive and irreversible destruction of the articular cartilage,which increases the friction significantly and causes further inflammation of the joint.Thus,a scaffold for articular cartilage defects should be developed via lubrication restoration and drug intervention.In this study,we successfully synthesized gelatin-based composite hydrogels,namely GelMA–PAM–PMPC,with the properties of biomimetic lubrication and sustained drug release by photopolymerization of methacrylic anhydride modified gelatin(GelMA),acrylamide(AM),and 2-methacryloyloxyethyl phosphorylcholine(MPC).Tribological test showed that the composite hydrogels remarkably enhanced lubrication due to the hydration lubrication mechanism,where a tenacious hydration shell was formed around the zwitterionic phosphocholine headgroups.In addition,drug release test indicated that the composite hydrogels efficiently encapsulated an anti-inflammatory drug(diclofenac sodium)and achieved sustained release.Furthermore,the in vitro test revealed that the composite hydrogels were biocompatible,and the mRNA expression of both anabolic and catabolic genes of the articular cartilage was suitably regulated.This indicated that the composite hydrogels could effectively protect chondrocytes from inflammatory cytokine-induced degeneration.In summary,the composite hydrogels that provide biomimetic hydration lubrication and sustained local drug release represent a promising scaffold for cartilage defects in the treatment of osteoarthritis. | Kuan ZHANG Jielai YANG Yulong SUN Yi WANG Jing LIANG Jing LUO Wenguo CUI Lianfu DENG Xiangyang XU Bo WANG Hongyu ZHANG | 2022 | Friction2022，10，2： | 1 |
| 9 | The hypoxia - inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development 显示文摘 | Wang Ying Chao Wan Lianfu Deng | 2007 | Clin Invest2007，117，： | 1 |
| 10 | Regulated macrophage immune microenvironment in 3D printed scaffolds for bone tumor postoperative treatment显示文摘The 3D printing technique is suitable for patient-specific implant preparation for bone repair after bone tumor resection.However,improving the survival rate due to tumor recurrence remains a challenge for implants.The macrophage polarization induction to M2-type tumor-associated macrophages(TAMs)by the tumor microenvironment is a key factor of immunosuppression and tumor recurrence.In this study,a regenerative scaffold regulating the macrophage immune microenvironment and promoting bone regeneration in a dual-stage process for the postoperative treatment of bone tumors was constructed by binding a colony-stimulating factor 1 receptor(CSF-1R)inhibitor GW2580 onto in situ cosslinked hydroxybutylchitosan(HBC)/oxidized chondroitin sulfate(OCS)hydrogel layer covering a 3D printed calcium phosphate scaffold based on electrostatic interaction.The hydrogel layer on scaffold surface not only supplied abundant sulfonic acid groups for stable loading of the inhibitor,but also acted as the cover mask protecting the bone repair part from exposure to unhealthy growth factors in the microenvironment at the early treatment stage.With local prolonged release of inhibitor being realized via the functional material design,CSF-1R,the main pathway that induces polarization of TAMs,can be efficiently blocked,thus regulating the immunosuppressive microenvironment and inhibiting tumor development at a low therapeutic dose.At the later stage of treatment,calcium phosphate component of the scaffold can facilitate the repair of bone defects caused by tumor excision.In conclusion,the difunctional 3D printed bone repair scaffold regulating immune microenvironment in stages proposed a novel approach for bone tumor postoperative treatment. | Cuidi Li Changwei Li Zhenjiang Ma Hongfang Chen Huitong Ruan Lianfu Deng Jinwu Wang Wenguo Cui | 2023 | Bioactive Materials2023，，1： | 1 |
| 11 | Effects of strontium in modified biomaterials显示文摘 | Weibin Zhang Yuhui Shen Haobo Pan Kaili Lin Xiaoguo Liu Brian W. Darvell William W. Lu Jiang Chang Lianfu Deng Deping Wang Wenhai Huang | 2010 | Acta Biomaterialia2010，，2： | 1 |
| 12 | In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy显示文摘In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases. | Yawei Du Chao Li Yu Zhang Wei Xiong Fei Wang Juan Wang Yingze Zhang Lianfu Deng Xinsong Li Wei Chen Wenguo Cui | 2023 | Research2023，，3： | 0 |
| 13 | Erythropoietin upregulates growth associated protein-43 expression and promotes retinal ganglion cell axonal regeneration in vivo after optic nerve crush显示文摘In this study, we established a rat model of optic nerve crush to explore the effects of erythropoietin on retinal ganglion cell axonal regeneration. At 15 days after injury in erythropoietin treated rats, retinal ganglion cell densities in regions corresponding to the 1/6, 3/6 and 5/6 ratios of the retinal radius were significantly increased. In addition, the number of growth associated protein-43 positive axons was significantly increased at different distances (50, 250 and 500 ?m) from the crush site after erythropoietin treatment. Erythropoietin significantly increased growth associated protein-43 protein levels in the retina after crush injury, as determined by western blot and immunofluorescence analysis. These results demonstrate that erythropoietin protects injured retinal ganglion cells and promotes axonal regeneration. | Haibo Tan Xin Kang Yisheng Zhong Xi Shen Yu Cheng Qin Jiao Lianfu Deng | 2012 | Neural Regeneration Research2012，7，4： | 0 |
| 14 | Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries显示文摘Central nervous system(CNS)injuries,including stroke,traumatic brain injury,and spinal cord injury,are essential causes of death and long-term disability and are difficult to cure,mainly due to the limited neuron regeneration and the glial scar formation.Herein,we apply extracellular vesicles(EVs)secreted by M2 microglia to improve the differentiation of neural stem cells(NSCs)at the injured site,and simultaneously modify them with the injured vascular targeting peptide(DA7R)and the stem cell recruiting factor(SDF-1)on their surface via copper-free click chemistry to recruit NSCs,inducing their neuronal differentiation,and serving as the nanocarriers at the injured site(Dual-EV).Results prove that the Dual-EV could target human umbilical vascular endothelial cells(HUVECs),recruit NSCs,and promote the neuronal differentiation of NSCs in vitro.Furthermore,10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis,and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs,miR30b-3p,miR-222-3p,miR-129-5p,and miR-155-5p may exert effect of inducing NSC to differentiate into neurons.In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice,potentiate NSCs recruitment,and increase neurogenesis.This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells,and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health. | Huitong Ruan Yongfang Li Cheng Wang Yixu Jiang Yulong Han Yiwei Li Dandan Zheng Jing Ye Gang Chen Guo-yuan Yang Lianfu Deng Ming Guo Xingcai Zhang Yaohui Tang Wenguo Cui | 2023 | Acta Pharmaceutica Sinica B2023，13，5： | 0 |
| 15 | Engineered extracellular vesicles for ischemic stroke treatment显示文摘Dear Editor,Nanotechnology-based therapeutic strategies have been proven effective in diseases including cancer,infection,inflammation,etc.1 However,the application of nanotechnology is greatly restricted in the treatment of central nervous system(CNS)disorders due to physiological CNS barriers.For example,the blood-brain barrier(BBB)can be the“Maginot line”for pharmacologically active molecules,blocking them out of the CNS. | Huitong Ruan Yongfang Li Dandan Zheng Lianfu Deng Gang Chen Xingcai Zhang Yaohui Tang Wenguo Cui | 2023 | The Innovation2023，4，2： | 0 |
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