Design Andpreparationof Injectable Hydrogel with High Mechanical Strength

Author:Qin Ze Zhao

Supervisor:yang xiao niu


Degree Year:2019





Hydrogels are a kind of polymer materials with 3D network structure which have high water content and similar properties as the natural extracellular matrix(ECM).Injectable hydrogel is a kind of hydrogel materials which could realize the in vitro injection and in vivo rapid gelation.It can be applied to target sites via minimally invasive delivery and fill irregular defects in vivo,also has the ability to encapsulate cells,drugs and bioactive molecules.Because of these outstanding advantages,injectable hydrogels are especially useful in tissue engineering and drug delivery.However,limited by the preparation requirements,injectable hydrogels always have poor mechanical properties.Besides,hydrogels would swell and degrade under physiological environment,which could further destroy their mechanical properties.The problems mentioned above have greatly hindered their real-world applications.In this dissertation,to develop injectable hydrogel with excellent mechanical performance,polymer chain and hydrogel structure were reasonably designed to realize three chief purposes in succession:the high mechanical strength of injectable hydrogel in vitro,the non-swelling property under physiological environment,the mechanical stability during the degradation process.These results would provide new strategies for the preparation of injectable hydrogels with high strength.The main contents and conclusions are as follows:Firstly,we proposed a new strategy to improve the mechanical property of injectable hydrogel through the self-aggregation of POSS end group.A POSS-capped polyethylene glycol-bisurea copolymer was synthesized,which could self-assemble into shear-thinning injectable hydrogel through hydrogen-bonding interaction of the bisurea.The hydrophobic aggregation of POSS end groups would function as another physical cross-linking,thus significantly enhancing the mechanical strength,thermal stability and anti-erosion property while not influencing the shear-thinning,self-healing properties and biocompatibility.Secondly,a novel strategy based on high-density and strong micelle cross-linkings is proposed to prepare nonswellable and tough hydrogel.To receive the strong micelle,the synergetic effect of hydrophobic and quadruple hydrogen-bonding interactions is employed by introducing an alkyl chain-protected ureido pyrimidinone moiety into a segmented copolymer backbone.The length of the alkyl and PEG molecular weight were carefully tailored to gain micelles with high strength and uniform distribution,which were used as cross-linkings to prepare hydrogels.The strong and high-density micelle cross-linkings restrain multiple effective chains outside the micelle from stretching during swelling,while the deformability of micelle cross-linkings disperses the local stress to maintain the network with high cross-linking density upon loading.The resultant hydrogel exhibited an outstanding non-swelling behavior under physiological conditions and excellent mechanical properties.Meanwhile,it also showed good tissue adhesion,cytocompatibility and suitable degradability.At last,we integrated micelle cross-linking and tetra-armed PEG as two kinds of cross-links in one system and developed a hydrogel with excellent mechanical performance and long-term stability.The hydrogel could be formed in an one-step mixing and displayed a compressive stress of 40 MPa at 95%strain without residual strain.What is more,the dual cross-linking strategy has not only made hydrogels non-swelling under diverse environments but also ensured the relative integrity of the gel network during degradation process,both of which working together to ensure the long-term mechanical stability of our hydrogel.Besides,dopamine(PDA)has been introduced to dual cross-linking hydrogel to improve the adhesive strength.The resultant hydrogels not only have high mechanical strength,but also show strong adhesion to different meterials.Because of the nonswellable property,the hydrogel could still maintain their high adhesive strength under water environment.