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Intelligent microneedle patch with prolonged local release of hydrogen and magnesium ions for diabetic wound healing

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Bioactive Materials 2023年第6期24卷 463-476页

作者： Pei Wang Jiayingzi Wu Haiyan Yang Hengke Liu Tianyu Yao Chang Liu Yan Gong Mingsong Wang Guangyu Ji Peng Huang Xiansong Wang Department of Thoracic Surgery Shanghai Key Laboratory of Tissue EngineeringShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai200011China Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Medical SchoolShenzhen518060China Center of Hydrogen Science Shanghai Jiao Tong UniversityShanghai200240China

Diabetes mellitus,an epidemic with a rapidly increasing number of patients,always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization,decreased angiogenesis and increased reactive oxygen species(ROS)in the microenvironment.Herein,a poly(lactic-co-glycolic acid)(PLGA)-based microneedle patch loaded with magnesium hydride(MgH_(2))(MN-MgH_(2))is manufactured for defeating diabetic wounds.The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH_(2) that can generate hydrogen(H_(2))and magnesium ions(Mg^(2+))after reaction with body fluids.The released H_(2) reduces the production of ROS,transforming the pathological microenvironment induced by diabetes mellitus.Meanwhile,the released Mg^(2+)promotes the polarization of pro-healing M2 macrophages.Consequently,cell proliferation and migration are improved,and angiogenesis and tissue regeneration are enhanced.Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H_(2) and Mg^(2+)locally and sustainably.

关键词： microneedle patch Magnesium hydride Hydrogen Magnesium ion Diabetic wound healing

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Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 284-297页

作者： Mengfang Wu Tian Xia Yaran Li Tianfa Wang Shijia Yang Jinchao Yu Qiaoyan Liang Teng Shen Min Yu Bing Zhao Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationFudan UniversityShanghai 200032China The Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan UniversityShanghai 200032China Key Laboratory of Smart Drug Delivery Ministry of EducationDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.

关键词： Anticoagulant r-hirudin microneedle patch 3D printing technology

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Scattered seeding of CAR T cells in solid tumors augments anticancer efficacy

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National Science Review 2022年第3期9卷 42-51页

作者： Hongjun Li Zejun Wang Edikan A.Ogunnaike Qing Wu Guojun Chen Quanyin Hu Tianyuan Ci Zhaowei Chen Jinqiang Wang Di Wen Hongwei Du Jie Jiang Jie Sun Xingcai Zhang Gianpietro Dotti Zhen Gu Department of Cell Biology and Bone Marrow Transplantation Center of the First Affiliated Hospital Zhejiang University School of Medicine John A. Paulson School of Engineering and Applied Sciences Harvard University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University College of Pharmaceutical Sciences Zhejiang University Liangzhu Laboratory Zhejiang University Medical Center Department of Bioengineering University of California Jonsson Comprehensive Cancer Center University of California California Nano Systems Institute University of California Center for Nanotechnology in Drug Delivery Eshelman School of Pharmacy University of North Carolina Lineberger Comprehensive Cancer Center University of North Carolina Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University Department of Microbiology and Immunology University of North Carolina

Chimeric antigen receptor T cell(CAR T) therapy was a milestone in the treatment of relapsed and refractory B cell malignancies. However, beneficial effects of CAR T cells have not been obtained in solid tumors yet. Herein, we implement a porous microneedle patch that accommodates CAR T cells and allows in situ penetration-mediated seeding of CAR T cells when implanted in the tumor bed or in the post-surgical resection cavity. CAR T cells loaded in the pores of the microneedle tips were readily escorted to the tumor in an evenly scattered manner without losing their activity. Such microneedle-mediated local delivery enhanced infiltration and immunostimulation of CAR T cells as compared to direct intratumoral injection. This tailorable patch offers a transformative platform for scattered seeding of living cells for treating a variety of tumors.

关键词： drug delivery CAR T therapy microneedle patch solid tumor treatment cell delivery

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