Construction Of Polyvinyl Alcohol/Glycerol Organohydrogel And Its Application On Reparation Of Intervertebral Disc Degeneration And Skin Wound

In this paper,a series of injectable organohydrogels based on polyvinyl alcohol and glycerol were prepared.Considering the different repair demands for intervertebral disc（IVD）degeneration and skin wounds,the organohydrogel scaffold and organohydrogel dressing were developed,respectively,and the systematic study for treating both two tissue injuries was conducted.The first part of the thesis（including the second and third chapters）discusses the organohydrogel scaffolds（OHS1,OHS2,and OHS3）with different content of PVA and in situ self-curing properties.The three scaffolds could transform from a fluid-like state into a viscoelastic-gel state after curing at room temperature for 4.3±0.1,2.4±0.2,and 1.3±0.2h,respectively.The storage moduli of OHS1,OHS2,and OHS3 after curing were 119.3±4.9,418.0±27.7 and 3659.0±205.4 Pa,respectively.Among the three organohydrogels,OHS2 exhibited a storage modulus similar to that of natural nucleus pulposus tissue（～307Pa）.After curing in a hyper-osmotic solution（aqueous polyvinyl pyrrolidone with a concentration of 0.15 g/m L）for 3 and 7 days,the compressive modulus changed minimally from 2.4±0.1 k Pa to 2.7±0.1 and 2.5±0.1 k Pa,respectively.This indicates that OHS2 can endure the hyper-osmotic environment of IVD（approximately 430–496 m Osm/kg）and has the potential to be a reliable IVD degeneration treatment.The results of in vitro biological tests revealed that OHS2 could support the long-term survival of nucleus pulposus cells（NPCs）,maintain the Col II expression of NPCs,and significantly reduce the apoptosis of NPCs in an inflammatory environment.The results of animal tests revealed that OHS2efficiently inhibited IVD degeneration by maintaining the height of IVD and the water content of nucleus pulposus.The second part of the thesis（including the fourth and fifth chapters）discusses an organohydrogel dressing（OHD）with moisture-holding and anti-freezing properties,which could be used for the wound care at drying and low-temperature environment.The water vapor transmission rate of the OHD is 428±9 g/m²?day,which is appropriate for both normal and defective skin.OHD as a curcumin-releasing carrier could release curcumin for 7 days,with a burst release period of only 12 h and a burst release ratio of only 23.9%.The results of the in vitro tests revealed that extract of curcumin-laden OHD（Cur-OHD）supported the survival of fibroblasts and promoted the proliferation of vein endothelial cells,and Cur-OHD exhibited good antibacterial properties against both S.aureus and E.coli.The results of animals experiment suggested that Cur-OHD effectively promoted wound healing.The wound contraction ratios of the Cur-OHD group were 67.4±8.4%,91.6±2.5%,and 93.7±3.6%at 5,10,and 15 days,respectively.Moreover,after 15 days,the epidermal thickness,collagen deposition ratio,blood vessel density,and blood vessel area ratio of the wound tissue in the Cur-OHD group were 63.0±6.6μm,60.7±3.8%,80.9±6.6 mm^-2,and 3.2±0.7%,respectively.This study demonstrated that PVA/glycerol organohydrogels are expected to be used as new cell-laden platforms or as dual-drug carriers for hydrophilic and hydrophobic drugs,with application potential in the fields of tissue engineering,regenerative medicine and organs-on-chips.