Regenerative antibacterial hydrogels from medicinal molecule for diabetic wound repair

Hydrogel products for chronic diabetic wounds,a serious and prevalent complication of diabetes,show limited effects on disability and remain nonspecific.Thus,improvements in the usage of pharmaceutical molecule in the hydrogels are highly desirable to increase the therapeutic effect of hydrogels.In this study,thioctic acid(a common medicine molecule in diabetes treatment)is used for preparing regenerative antibacterial hydrogels(RAH)which contains in situ synthesized silver nanoparticles(AgNPs).The RAH shows regenerative,self-healing and injectable ability,because of the reversible hydrogen and coordination bonds.With good regenerative capacity,RAH can be stored as powder to avoid the water loss and facilitate storage availability.Owing to the antioxidant properties of thioctic acid,the RAH can decrease the oxidative damage and retain cell proliferation efficiency.Due to the in situ synthesized AgNPs,the RAH also exhibits extraordinary antimicrobial capacities against MDR bacteria.All of these superiorities enable RAH to be a promising therapy for chronic diabetic wounds.

Preparation, Swelling and Antibacterial Behaviors of N-Succinyl Chitosan-g-Poly(Acrylic Acid-co-Acrylamide) Superabsorbent Hydrogels

Superabsorbent hydrogels were prepared successfully from N-succinyl chitosan grafted poly（acrylic acid-co-acrylamide）. The potassium persulfate（KPS）, N, N＇-methylenebisacrylamide（MBA） were used as the initiator and crosslinker, respectively. Fourier transform infrared spectroscopy（FTIR） and scanning electron microscopy（SEM） were used to confirm the porous network structure of superabsorbent hydrogel. The effects of reaction parameters on the swelling behaviors of the superabsorbent hydrogels were investigated. The results indicated that water absorbency increased first, and then decreased gradually with the increase in the contents of monomer（AA＋AM）, KPS, MBA or acrylamide. The product had excellent water absorbency of 1375 g/g in distilled water and 83 g/g in 0.9wt% NaCl solution. Simultaneously, the superabsorbent hydrogels were p H sensitive. The antibacterial activities of the hydrogels against Escherichia coli（E. coli） were improved effectively because of polyamidoamine（PAMAM） dendrimer absorbed in the hydrogels.

Preparation and Properties of Poly(amidoamine) Dendrimer/Quaternary Ammonium Chitosan Hydrogels

A novel quaternary ammonium chitosan hydrogel modified by poly（amidoamine）（PAMAM） dendrimer was prepared by using glutaraldehyde as a cross-linker. The hydrogel was characterized by Fourier transform infrared spectroscopy（FTIR） and scanning electron microscopy（SEM）. The results confirmed its highly porous three-dimensional network structure. The swelling test of hydrogel proved that it had excellent swelling and p H-sensitive properties. The increasing PAMAM content or quaternization degree led to the increase in swelling properties. And the hydrogel with lower cross-linking agent concentration or quaternary ammonium chitosan concentration exhibited better swelling properties. The antibacterial results indicated that with the increase in the PAMAM content, quaternary ammonium chitosan concentration or cross-linking agent concentration, the hydrogels showed better antibacterial activities against both Staphylococcus aureus（S. aureus） and Escherichia coli（E. coli）. Thus, the hydrogel could serve as a promising antibacterial material in the future.

Mussel-inspired nanozyme catalyzed conductive and self-setting hydrogel for adhesive and antibacterial bioelectronics

Adhesive hydrogels have broad applications ranging from tissue engineering to bioelectronics;however,fabricating adhesive hydrogels with multiple functions remains a challenge.In this study,a mussel-inspired tannic acid chelated-Ag(TA-Ag)nanozyme with peroxidase(POD)-like activity was designed by the in situ reduction of ultrasmall Ag nanoparticles(NPs)with TA.The ultrasmall TA-Ag nanozyme exhibited high catalytic activity to induce hydrogel self-setting without external aid.The nanozyme retained abundant phenolic hydroxyl groups and maintained the dynamic redox balance of phenol-quinone,providing the hydrogels with long-term and repeatable adhesiveness,similar to the adhesion of mussels.The phenolic hydroxyl groups also afforded uniform distribution of the nanozyme in the hydrogel network,thereby improving its mechanical properties and conductivity.Furthermore,the nanozyme endowed the hydrogel with antibacterial activity through synergistic effects of the reactive oxygen species generated via POD-like catalytic reactions and the intrinsic bactericidal activity of Ag.Owing to these advantages,the ultrasmall TA-Ag nanozyme-catalyzed hydrogel could be effectively used as an adhesive,antibacterial,and implantable bioelectrode to detect bio-signals,and as a wound dressing to accelerate tissue regeneration while preventing infection.Therefore,this study provides a promising approach for the fabrication of adhesive hydrogel bioelectronics with multiple functions via mussel-inspired nanozyme catalysis.

Electrospinning of antibacterial and anti-inflammatory Ag@hesperidin core-shell nanoparticles into nanofibers used for promoting infected wound healing

Bacterial infection and excessive inflammation are still the main obstacles to wound repair.Thus,antibacterial and antiinflammation nanomaterials are always attracting for infected wound healing.In this work,ultra-uniform(-20 nm)and colloidally stable Ag nanoparticles(Ag-Hes NPs)with core-shell structure were prepared by using hesperidin as reducing and capping agent.The obtained Ag-Hes NPs present effective antibacterial properties on both Staphylococcus aureus and Escherichia coli.Ag-Hes NPs also got high 1,1-diphenyl-1-picrylhydrazyl scavenging capability of 69%.Under the package of polyvinyl alcohol and sodium alginate,Ag-Hes NPs were encapsulated into electro spun nanofibers to form hydrogel(Ag-Hes@H).This strategy provides a moisture environment which could enrich and release Ag-Hes NPs gradually.Cell experiments and animal wound healing investigation proved that Ag-Hes@H could promote the proliferation and migration of human umbilical vein endothelial cells and accelerate infected wound healing.Meanwhile,Ag-Hes@H significantly reduced the expression of inflammatory cytokines,including IL-6,MMP9 and TNF-α.Immunohistochemistry data further suggested that Ag-Hes@H accelerated wound closure by promoting collagen deposition and skin cell proliferation.The designed antibacterial and anti-inflammatory Ag-Hes@H has great potential for promoting infected wound healing.

All-small-molecule supramolecular hydrogels assembled from guanosine 5′-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis

Bacterial keratitis is the most common corneal infection which may lead to blindness,and seriously threatened the human visual health worldwide.Clinical treatment with antibiotic eye drops formulation usually falls in low bioavailability and poor therapeutic efficiency.Hydrogel has gained much attention as ophthalmic formulation recently due to the prolonged drug retention on ocular surface.In this study,we proposed a type of all-small-molecule supramolecular hydrogel assembled from guanosine-5′-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis.Guanosine-5′-monophosphate disodium salt assembled into guanosine-quartet nanofibers via hydrogen bonding andπ-πstacking,and tobramycin with five primary amine groups further crosslinked the nanofibers bearing multiple phosphate moieties into gel networks via ionic interactions.The supramolecular gel showed shear thinning and thixotropic properties,good biocompatibility,and antibacterial activity.The gel treatment significantly ameliorated P.aeruginosa induced bacterial keratitis,and showed higher therapeutic efficacy compared to tobramycin eye drop.This study provides a facile and efficient antibiotic gel formulation for clinical treatment of bacterial keratitis.