Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and ...Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.展开更多
Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided...Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:11972099,82202340Venture&Innovation Support Program for Chongqing Overseas Returnees,Grant/Award Number:cx2020079Scientific and Fundamental Research Funds for the Central Universities,Grant/Award Numbers:2023CDJXY-050,2023CDJXY-051。
文摘Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.
基金The authors acknowledge the financial assistance provided by the National Natural Science Foundation of China(11972099 and 31600770)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2020079)+2 种基金the Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education(CQKLBST-2017-008)the research and development talent base subject of advantageous traditional Chinese medicine in Bijie City,Guizhou Province(RCJD2020-21)the projects in the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(2015BAI05B03).
文摘Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.
