Preparation And Properties Of Natural Polysaccharide Based Physically Crosslinked Double-network Hydrogels

Hydrogel has the physical and chemical properties similar to that of extracellular matrix,which can be artificially adjusted.It has strong hydrophilicity,high water content and large porosity.It is widely used in many biomedical tracks such as wound dressing,drug delivery and tissue engineering,as well as industrial,environmental and other fields.In recent years,natural polysaccharides and their derivatives,such as sodium alginate(SA)and chitosan(CS),have been widely used in the preparation of functional natural hydrogels because of their rich sources,no immunogenicity,good biodegradability and biocompatibility.However,the mechanical properties of most natural hydrogels are insufficient,and they are soft and brittle,which limits the further application of natural hydrogels.Double-network hydrogel is an effective solution to improve the mechanical properties of natural hydrogels.However,most doublenetwork hydrogels have added chemical crosslinkers which usually damage the biocompatibility of hydrogels,bring cytotoxicity to hydrogels,and affect the biodegradability of hydrogels.Therefore,the development of completely physically crosslinked double-network hydrogels can avoid the excessive use of toxic chemicals,enhance the mechanical properties of hydrogels,and promote the application of hydrogels in biomedicine and other fields.In this study,natural polysaccharides such as sodium alginate(SA),chitosan(CS)and its derivative chitosan oligosaccharides(COS)and various divalent metal cations were used as raw materials to prepare completely physically crosslinked doublenetwork hydrogels and hydrogel films without any chemical crosslinking agents.A series of systematic in vitro and in vivo experiments were carried out to characterize and test the structure,physical properties and biological properties of these two materials.The experimental results confirmed their potential as wound dressings.The main contents of this study are as follows:(1)A new environment-friendly sodium alginate/chitosan/zinc ion physically crosslinked double-network hydrogel(SA/CS/Zn2+PDH)was prepared by semidissolution acidification sol-gel transition method and internal gelation method.The disappearance and migration of the original characteristic peak and the generation of new characteristic peak were found in the Fourier transform infrared spectrum,the results confirmed the formation and internal interaction of SA/CS/Zn2+PDH.Scanning electron microscopy results confirmed that SA/CS/Zn2+ PDH has a homogeneous pore structure.Gelation time,water content and swelling ability of the hydrogel were evaluated with zinc concentration as a variable,these experimental results showed that with the increase of zinc content,the gelation rate increased rapidly,and the water content and swelling rate decreased slightly.SA/CS/Zn2+double-network hydrogel showed better mechanical properties than SA/CS single network hydrogel and SA/Zn2+single network hydrogel,the compression modulus of SA-CS-30 group reached 48 Kpa.In vitro antibacterial experiments confirmed that SA/CS/Zn2+PDH had excellent antibacterial activity against both Staphylococcus aureus and Escherichia coli.The diameter of bacteriostatic ring of SA-CS-30 group reached 31.7 mm,which was 2.1 times the diameter of hydrogel itself.CCK-8 cytotoxicity experiment confirmed that SA/CS/Zn2+PDH was non-toxic at the experimental concentration,and the optimum concentration of zinc ion was about 20 mM.The results of animal experiments and HE staining showed that the hydrogel had the ability to promote wound healing.(2)On the basis of experiment(1),chitosan oligosaccharides/sodium alginate/multi metal ion physically crosslinked multifunctional.double-network hydrogel film(COS/SA/nM2+PDF)was prepared in situ by delayed spray method.Compared with chitosan,chitosan oligosaccharide has more excellent biological activity and better water solubility.In this study,we introduced a variety of divalent metal cations such as Ca2+、Zn2+and Sr2+,in order to integrate the advantages of these metal ions through compounding.Through a series of experiments,we systematically characterized and evaluated the structure,physical properties,antibacterial performance,antioxidant performance,cytocompatibility and the ability to promote wound healing of COS/SA/nM2+PDF.The experimental results confirmed that the hydrogel films with different metal ions exhibit different characteristics.For example,the 3%COS-Ca2+Zn2+-Sr2+group had the densest structure,the largest tensile strength and better thermal stability;The 3%COS-Ca2+-Zn2+group reached the maximum swelling rate fastest and the swelling rate was the highest(2 h,14000%);Within 24 hours,3%COS-Ca2+-Sr2+group had the strongest ability to promote cell proliferation(140%);3%COS-Zn2+-Sr2+group had the most significant effect on bacteriostasis and wound healing,and so on.COS/SA/nM2+PDF can provide more diversified dressing choices for different conditions of wounds.In summary,our work provides a new idea for the fabrication of environmentfriendly physically crosslinked double-network hydrogels and hydrogel films based on natural polysaccharides.