| Hydrogels are three-dimensional cross-linked networks formed by hydrophilic molecule.There is great diversity in hydrogel formulations,such as natural polysaccharides(cellulose,alginic acid,chitosan),polypeptide(poly-L-lysine,poly-L-glutamine),and synthetic polymer(acrylic acid,poly methacrylic acid,polyacrylamide),etc.Among them,peptides-based hydrogels have attracted the attention of researchers due to their excellent biocompatibility,degradability,and editable biological function.Jelleine-1(J-1)was isolated from the royal jelly of honeybees,and it showed potent activity against bacteria and fungi.We found that J-1 could self-assemble into self-supporting hydrogels in some salt solutions with specific functions.For example,the J-1-8Br-c AMP hydrogel,J-1 formed in 8Bromoadenosine-cyclic adenosine monophosphate(8Br-c AMP)phosphate solution,could promote wound healing by enhancing the secretion of the growth factors.As an intracellular second messenger,c AMP regulates various physiological functions of the body.8Br-c AMP,a derivative of c AMP,could promote the secretion of growth factors from cells.The J-1-ADP hydrogel formed by J-1 in adenosine diphosphate(ADP)sodium salt solution showed potent hemostatic and anti-adhesion activity.ADP was the first discovered and the most important substance inducing platelet aggregation in the human body.This study reported the characterization,biocompatibility,and biological function of the hydrogels formed by J-1 in phosphate buffered solution(PBS),8Br-c AMP phosphate solution,and ADP sodium salt solution,respectively.1.We explored the J-1-PBS hydrogel through the vial inversion,field emission scanning electron microscope,rheology,nuclear magnetic resonance,fluorescence spectroscopy,and Fourier transform infrared spectroscopy.The results showed that J-1-PBS hydrogel was formed by the physical crosslinking of J-1 nanofibers in PBS without any other chemical crosslinkers.Moreover,J-1-PBS hydrogel showed good mechanical and injectable properties,which could form a physical barrier on the surface of irregular burn wounds and provide a moist environment for wound healing.Then,we investigated its activity and biocompatibility in vitro and in vivo.J-1-PBS hydrogel exhibited good antimicrobial activity against S.aureus,E.coli,C.albicans,and MRSA.In addition,it exhibited good biocompatibility in vitro and in vivo.Notably,the hydrogel showed great potential in promoting MRSA infected burn wound healing by reducing the number of bacteria and inflammatory responses in the wound.This study would provide an inherent antimicrobial hydrogel dressing without loading antibiotics for infected wounds,broaden the application of antimicrobial peptides,and pave an alternative strategy for the design of antimicrobial hydrogel.2.J-1-8Br-c AMP hydrogel not even exhibited excellent antimicrobial activity,but it was proved that it could promote the secretion of basic fibroblast growth factor,hepatocyte growth factor,transforming growth factor-β,vascular endothelial growth factor-A,and cell migration.Notably,it exhibited potent potential for promoting MRSA infected diabetic wound healing by reducing the number of bacteria,alleviating inflammatory response of the wound,and promoting the secretion of growth factors in the surrounding wound tissues.Given that infection and insufficient supply of growth factors are the main causes of refractory wounds,such as diabetic wounds,J-1-8Br-c AMP hydrogel could be an effective wound dressing for the refractory wounds.3.Due to ADP being a platelet-activating factor,J-1-ADP hydrogel showed significant hemostatic activity in vitro verified by the whole blood coagulation,plasma coagulation,platelet activation,and platelet adhesion assays.Further,it showed potent hemostatic activity in a mouse liver hemorrhage model.Bleeding was believed to be a cause of the formation of post-surgery adhesion,so we studied its anti-adhesion effect by establishing a rat side wall defect-cecum abrasion model.As expected,the J-1-ADP hydrogel behaved with a significant anti-adhesion effect in vivo.In addition,it had good mechanical properties,antibacterial activity,biocompatibility,and degradation properties.So,the present study may provide an alternative hydrogel material for hemostasis and preventing postoperative adhesion in the clinic.In conclusion,we prepared J-1-PBS hydrogel with antimicrobial activity,J-1-8Br-c AMP hydrogel with promoting wound healing effect,and J-1-ADP hydrogel with hemostatic activity and anti-adhesion effect.All hydrogels were prepared by J-1assembling directly in different salt solutions without other chemical cross-linking agents and functional active molecules.The present study provided potential materials for infected burn,infected diabetic wounds,and tissue adhesion.In addition,the research can also provide the basis and new strategy for the construction of functional hydrogels. |
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