Development Of A New Exocrine Hydrogel For Prevention And Treatment Of Skin Photoaging

The contradiction has deepened day by day between skin photoaging and human’s pursuit of beauty.How to effectively prevent skin photoaging is a great challenge for scientific researchers at present.Photoaging is a long-term skin damage caused by sunlight,which is usually accompanied by skin relaxation,deep and thick wrinkles,dry desquamation,and increased number of melanocytes.Topical drugs,laser,injection and filling are the main clinical methods for the prevention and treatment of skin photoaging,which have some problems such as strong irritation,poor permeability and high price.Therefore,it is urgent to develop and construct an efficient and gentle prevention and treatment strategy.Existing studies have shown that UV radiation is a key factor in accelerating the production of oxygen free radicals(ROS)in the skin,which disrupts the antioxidant capacity of cells and the skin’s natural antioxidant barrier system.Exosomes not only have immune regulation and tissue regeneration functions,but also possess immune privileges suitable for preventing and treating skin photoaging due to their membrane structure and intrinsic composition similar to the original source cells.However,the defect that exosomes are easily cleared by the body prematurely limits its application in regenerative medicine.In this study,the exosomes derived from 3D cultured human dermal fibroblasts(HDFExo3D)were selected as contents,and ROS response hydrogels(CMCTs-TK/HA@exo3D)formed by carboxymethyl chitosan(CMCTS)crosslinking with oxidative hyaluronic acid(HA)and thioketal(TK)were used to encase exosomes in order to prevent and treat skin photoaging.By means of fourier transform infrared spectroscopy,rheological analysis and nuclear magnetic resonance hydrogen spectroscopy,we successfully prepared and screened hydrogel scaffolds with concentrations of oxidized HA(3% w/v)and CMCTS(4% w/v),which could be proved from both structural and mechanical properties.Exosome release tests showed that hydrogels could effectively consume ROS,and the ROS concentration was proportional to the number of exosomes released.The establishment of cell proliferation experiments showed that the hydrogel system encapsulated exosomes had a higher ability to promote cell proliferation.Hydroxyproline content and collagen distribution in tissues were qualitatively and quantitatively analyzed by building a simple mouse photoaging model.Compared with the control group,the hydrogel containing exosomes could be directly injected into the target site,which could ensure a more concentrated exosome dose and provide sustained and obvious therapeutic effect.It has been shown that this oxidation-responsive hydrogel(CMCTs-TK/HA)based on the cross-linking of oxidized hyaluronic acid and carboxymethyl chitosan is a promising targeted exosome delivery system,which can prevent the premature removal of exosomes and improve their bioavailability.At the same time,it provides a new idea for effectively improving skin photodamage and preventing skin photoaging.