Preparation And Properties Of Degradable POSS-PEG Hybrid Hydrogels

Hydrogels have been widely used in tissue engineering and drug delivery due to the attractive features,including superior hydrophilicity,high biocompatibility,tissue-like softness and lack of immunogenicity.Polyethylene glycol(PEG)is nontoxic,can be excreted by the kidneys,and does not accumulate in the body.It is a widely used material to prepare hydrogel.At the same time,the degradable group or fragment can be introduced into the PEG chain to impart degradability to the PEG hydrogel.However,the low mechanical properties of PEG hydrogel limit its application as a scaffold for tissue engineering.Polyhedral oligomeric silsesquioxanes(POSS)are a family of inorganic-organic hybrid molecules which consist of a cage-like inorganic core and eight variable organic vertex groups.Because POSS has the quantum size effect and high surface energy,it is endowed with special dielectric properties,thermodynamic properties and strong hydrophobic properties.The introduction of POSS into polymer can significantly improve the basic properties of polymer,allowing POSS to have the ability to improve polymer performance at the molecular level.In addition,POSS is nontoxic,odorless and has good biocompatibility.It is an ideal hybrid material for medical polymer.In this thesis,a series of hydrolytically degradable POSS-PEG hybrid hydrogels,which POSS were covalently incorporated into as suspending nanoparticles to increase the mechanical properties,were prepared by covalently grafting hydrophobic thiol-functionalized POSS onto hydrophilic 4-arm-PEG-maleimide to form an amphipathic precursor and further cross-linking with hydrolytically PEG-diester-dithiol via Michael-type addition in low concentration TEA.And then the properties of the prepared hybrid hydrogels were investigated.Finally,the effects of different POSS-PEG hybrid hydrogels on cell proliferation and growth were explored.This thesis mainly divided into two parts:1.Firstly,synthesize different molecular weight of chain-like hydrolyzable thiol-functionalized PEG crosslinkers and investigate the effect of different cross-linking agents and different solid content on the formation of hybrid hydrogels to find the optimal gelation conditions.POSS-PEG hybrid hydrogels with different POSS content were prepared under the optimal conditions and their properties of microcosmic morphology,mechanical properties,swelling properties and degradation performance were investigated.The results show that all hybrid hydrogels have porous,three-dimensional crosslinked structures,and the pore size decreases with the increase of POSS content.The covalent introduction of POSS can increase the mechanical properties of hybrid hydrogels and reduce the swelling and degradation rate of hybrid hydrogels.Therefore,a series of properties of the hydrogels can be regulated by adjusting the POSS content in the hybrid hydrogels.2.On the basis of the first part,the hydrolysis rate of the POSS-PEG hybrid hydrogels is still obviously large,more effective measures are needed to regulate the hydrolysis rate of hybrid hydrogels effectively and prolong the degradation cycle of the hybrid hydrogel to meet the requirements of tissue engineering.Therefore,the method of mixed crosslinkers was used to prolong the degradation cycle of the hydrogel.Based on the first part,POSS content was fixed at 4%,the solid content was fixed at 7.5%,and the average molecular weight of the degradable thiol-functionalized PEG crosslinker was fixed at 4 KDa.POSS-PEG hybrid hydrogels with different degradation cycles were prepared in the same method as the first part,other than by using degradable thiol-functionalized PEG and non-degradable thiol-functionalized PEG chains as mixed crosslinkers.Then,the degradation properties and the micromorphology of different hydrogels were tested.Finally,the human umbilical vein endothelial cells(HUVEC)were 3D encapsulated in hybrid hydrogel to explore the cytotoxicity of hybrid hydrogels.The results showed that the degradation rate of POSS-PEG hydrogels could be greatly prolonged by adjusting the ratio of two crosslinker.The cytotoxicity experiment showed that the human umbilical vein endothelial cells grew well in the hybrid hydrogels,and the different degradation rate of the hybrid hydrogels has different effects on the growth of the human umbilical vein endothelial cell.In conclusion,a series of hydrolytically degradable POSS-PEG hybrid hydrogels with different POSS content,different ratio of degradable crosslinker were prerared and their mechanical properties,swelling properties,microstructure and biocompatibility were investigated,which can provide theoretical support and practical guidance to the applicaion of POSS-PEG hydrogels in tissue engineering.