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 ...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.展开更多
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 ...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.展开更多
基金A.S.would like to acknowledge the financial support from the Canadian Institutes of Health Research(CIHR)through a postdoctoral fellowship as well as the startup fund from The Pennsylvania State UniversityA.K.would like to acknowledge funding from the National Institutes of Health(1R01EB023052,1R01HL140618,CA257558,DK130566).We acknowledge UCLA CFAR grant 5P30 AI028697 and the UCLA AIDS Institute.The authors thank Profs.S.Li and M.Butte at UCLA for providing cryo-sectioning equipment and lab space for the blood coagulation tests,respectively.The authors also thank Prof.K.J.Lee for his advice on microneedle fabrication.
文摘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.
基金Dr.M.Ermis and Dr.N.Falcone contributed equally to this work.The authors gratefully acknowledge the funding by the National Institutes of Health(HL140951,HL137193,CA257558,DK130566)Dr.M.Ermis acknowledges The Scientific and Technological Research Council of Turkiye for 2219-International Postdoctoral Research Fellowship Program.
文摘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.
