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Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment

Bioactive Materials 2023年第5期23卷 314-327页

作者： reihaneh haghniaz Han-Jun Kim Hossein Montazerian Avijit Baidya Maryam Tavafoghi Yi Chen Yangzhi Zhu Solmaz Karamikamkar Amir Sheikhi Ali Khademhosseini Department of Bioengineering University of CaliforniaLos Angeles410 Westwood PlazaLos AngelesCA90095United States California NanoSystems Institute University of CaliforniaLos Angeles570 Westwood PlazaLos AngelesCA90095United States Terasaki Institute for Biomedical Innovation 11570 W Olympic BoulevardLos AngelesCA90024United States Department of Chemical Engineering The Pennsylvania State UniversityUniversity ParkPA16802United States Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA16802United States

Blood loss by hemorrhaging wounds accounts for over one-third of~5 million trauma fatalities worldwide every year.If not controlled in a timely manner,exsanguination can take lives within a few minutes.Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need.Here,biocompatible,and biodegradable microneedle arrays(MNAs)based on gelatin methacryloyl(GelMA)biomaterial hybridized with silicate nanoplatelets(SNs)are developed for hemorrhage control.The SNs render the MNAs hemostatic,while the needle-shaped structure increases the contact area with blood,synergistically accelerating the clotting time from 11.5 min to 1.3 min in vitro.The engineered MNAs reduce bleeding by~92%compared with the untreated injury group in a rat liver bleeding model.SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro-and nanoengineered features.Furthermore,the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications.These hemostatic MNAs may enable rapid hemorrhage control,particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.

关键词： Hemostat Microneedles Hemorrhage Bleeding Gelatin methacryloyl Silicate nanoplatelets

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Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer

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Bioactive Materials 2023年第7期25卷 360-373页

作者： Menekse Ermis Natashya Falcone Natan Roberto de Barros Marvin Mecwan reihaneh haghniaz Auveen Choroomi Mahsa Monirizad Yeji Lee Jihyeon Song Hyun-Jong Cho Yangzhi Zhu Heemin Kang Mehmet R.Dokmeci Ali Khademhosseini Junmin Lee Han-Jun Kim Terasaki Institute for Biomedical Innovation(TIBI) Los AngelesCA90024USA Department of Materials Science and Engineering Pohang University of Science and Technology(POSTECH)PohangGyeongbuk37673Republic of Korea College of Pharmacy Kangwon National UniversityChuncheonGangwon24341Republic of Korea Department of Materials Science and Engineering Korea UniversitySeoul02841Republic of Korea Institute for Convergence Research and Education in Advanced Technology Yonsei UniversityIncheon 21983Republic of Korea College of Pharmacy Korea UniversitySejong30019Republic of Korea

The tumor microenvironment consists of diverse,complex etiological factors.The matrix component of pancreatic ductal adenocarcinoma(PDAC)plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness.Although significant efforts have been made to model desmoplastic PDAC,existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC.Here,two major components in desmoplastic pancreatic matrices,hyaluronic acid-and gelatin-based hydrogels,are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts(CAF).Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation.Higher expression levels of markers associated with proliferation,epithelial to mesenchymal transition,mechanotransduction,and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels,while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1(TGF-β1).The proposed multicellular pancreatic tumor model,in combination with proper mechanical properties and TGF-β1 supplement,makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors,which could be potentially applicable for realizing personalized medicine and drug testing applications.

关键词： Pancreatic cancer Desmoplasia Fibrosis Extracellular matrix Tumor microenvironment

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Recent advances in biopolymer-based hemostatic materials

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Regenerative Biomaterials 2022年第1期9卷 1080-1105页

作者： Marvin Mecwan Jinghang Li Natashya Falcone Menekse Ermis Emily Torres Ramon Morales Alireza Hassani reihaneh haghniaz Kalpana Mandal Saurabh Sharma Surjendu Maity Fatemeh Zehtabi Behnam Zamanian Rondinelli Herculano Mohsen Akbari Johnson V.John Ali Khademhosseini Terasaki Institute for Biomedical Innovation Los AngelesCA 90064USA Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Department of Biomedical Engineering University of Southern CaliforniaLos AngelesCA 90089USA Bioengineering&Biomaterials Group School of Pharmaceutical SciencesSao Paulo State University(UNESP)AraraquaraSP 14800-903Brazil Department of Mechanical Engineering University of VictoriaVictoriaBC V8P 5C2Canada Biotechnology Center Silesian University of TechnologyGliwice 44-100Poland

Hemorrhage is the leading cause of trauma-related deaths,in hospital and prehospital settings.Hemostasis is a complex mechanism that involves a cascade of clotting factors and proteins that result in the formation of a strong clot.In certain surgical and emergency situations,hemostatic agents are needed to achieve faster blood coagulation to prevent the patient from experiencing a severe hemorrhagic shock.Therefore,it is critical to consider appropriate materials and designs for hemostatic agents.Many materials have been fabricated as hemostatic agents,including synthetic and naturally derived polymers.Compared to synthetic polymers,natural polymers or biopolymers,which include polysaccharides and polypeptides,have greater biocompatibility,biodegradability and processibility.Thus,in this review,we focus on biopolymer-based hemostatic agents of different forms,such as powder,particles,sponges and hydrogels.Finally,we discuss biopolymer-based hemostatic materials currently in clinical trials and offer insight into next-generation hemostats for clinical translation.

关键词： hemostasis coagulation polysaccharides polypeptides biomaterials

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