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
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 ...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.展开更多
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.
基金would like to acknowledge funding from the National Institute of Health(5R01HL137193).
文摘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.
