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1.
Carbohydr Polym ; 279: 118778, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34980345

ABSTRACT

Eliminating biofilms from infected tissue presents one of the most challenging issues in clinical treatment of chronic wounds. In biofilms, the extracellular polymeric substances (EPS) form gel structures by electrostatic forces between macromolecules. We hypothesized that cationic polymers could induce the gel-to-sol phase transition of the network, leading to biofilms disruptions. We first validated this assumption by using polyethyleneimine (PEI) as a model molecule, and further synthesized two cationic dextrans with high biodegradability for in vitro and in vivo evaluation. All the cationic polymers could destruct Pseudomonas aeruginosa (P. aeruginosa) biofilms. Treating biofilm with cationic dextrans significantly enhanced the bacterial antibiotic sensitivity. When tested in a biofilm-presenting mouse wound healing model, the cationic dextrans efficiently controlled infection, and accelerated the healing process. Our findings suggest that devising cationic polymers to trigger phase transition of biofilm is an effective, straightforward, and perhaps generic strategy for anti-bacterial therapies.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Dextrans/pharmacology , Hydrogels/pharmacology , Pseudomonas aeruginosa/drug effects , Alginates/chemistry , Animals , Cell Line , Cell Survival/drug effects , Cytokines/immunology , Dextrans/chemistry , Female , Hydrogels/chemistry , Mice, Inbred BALB C , Phase Transition , Polyethyleneimine/chemistry , Pseudomonas Infections/drug therapy , Pseudomonas Infections/immunology , Pseudomonas aeruginosa/physiology , Skin/drug effects , Skin/immunology , Wound Infection/drug therapy , Wound Infection/immunology
2.
Adv Sci (Weinh) ; 6(6): 1801694, 2019 Mar 20.
Article in English | MEDLINE | ID: mdl-30937263

ABSTRACT

Although pancreatic islet transplantation holds promise for the treatment of type I diabetes, its application has been significantly hampered by transplant rejection. Here, an approach is demonstrated to support trans-species islet beta cells from a rat to grow and function in the body of a mouse host while overcoming graft rejection. This approach, which builds on remodeling of the mouse testicle by local injection of a tumor homogenate, establishes an immunosuppressive and proregenerative niche in the testicle. This remodeling proves necessary and effective in shaping the testicle into a unique site to accommodate xenograft cells. Rat pancreatic beta cells-from both the insulinoma (cancer cells) and pancreatic islet (normal tissue)-survive, grow, and form a desirable morphology in the remodeled mouse testicle. Notably, when hyperglycemia is induced in the host body, these xenografts secrete insulin to regulate the blood glucose level in mice for as long as 72 days. Furthermore, no graft rejection, acute inflammation, or safety risks are observed throughout the study. In summary, it is demonstrated that the growth of xenogeneic insulinoma cells in a mouse testicle might serve as an alternative approach for islet transplantation.

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