Use Dynamic Covalent Bonds To Fabricate Injectable Self-healing Hydrogels

Injectable hydrogels have been commonly used as drug-delivery vehicles and tried in tissue engineering.These material systems are aqueous solutions before administration,and can rapidly gel as soon as injected to the target site under physiological conditions.This in situ formation process brings about some advantages,such as ease of administration,easy to embed drugs,and can be adaptable to complicate geometries requirements.Since external mechanical force may cause serious damage of the implanted hydrogels,and once disruption takes place in vivo,it may cause serious problems,hydrogels with self-healing ability,whose gel matrix could be quickly recovered after deformation,would be of great value.In this dissertation,we mainly focused on the development of new strategies for preparing injectable self-healing materials using dynamic chemistry as a tool.Specifically,the dissertation can be categorized into following three parts:we developed a new type of injectable hydrogel based on self-assembly of chain extended F127(PEO90-PPO65-PEO90)multi-block copolymer(m-F127)with rapid self-healing properties through dynamic covalent bonds between acylhydrazine and aldehyde groups.After oligomerization of aldehyde-terminated F127 triblocks using adipic dihydrazide(ADH)as a chain extender,multi-block copolymers with acylhydrazone bonds were formed.The solution of the multi-block copolymers still maintained the thermo-sensitivity,and thus could be injected with a low viscosity and then exhibit a fast thermo-responsive sol-to-gel transition at body temperature(37?).Moreover,the hydrogel possesses self-healing property under mild conditions based on the reversibly breaking and regenerating of acylhydrazone bonds.In addition,the m-F127 hydrogel has much stronger mechanical strength and longer erosion time in lower concentration compared with original F127 hydrogel.We prepared an injectable thermo-responsive hydrogel with excellent mechanical properties and self-healing ability by mixing a thiol functionalized F127 and dithiolane modified PEG in water.We have found that the cross-linked F127 hydrogel remained the thermo-responsibility as the native F127 polymer,which could undergo sol-gel transition in response to temperature,and thus could be injected at lower temperature with a low viscosity and then rapid gel at body temperature(37oC)at the site of administration.Moreover,due to the ring tension of the cyclic disulfide,the reactivity of the disulfide bonds was increased which made the hydrogel can self-heal at mild acid to alkaline conditions.Considering that disulfides have no cytotoxicity and are commonly found in biological systems such as proteins,this kind of hydrogel would be.of greater potential use in a number of fields such as drug delivery,tissue engineering and controlled 3D cell culture etc.We reported a new strategy to build a dynamic interpenetrating hydrogel with tunable mechanical properties and dual pH-responsive self-healing abilities.An acrylhydrazone cross-linked network and a boronate ester cross-linked network orthogonally gelated from a single double-barrel syringe administration and resulted in a fully interpenetrating hydrogel.The gelation time and mechanical properties can be tuned by pH or the solid content.Since acrylhydrazone and boronate ester can exchange at different pH values,the hydrogel can self-heal at both acidic and basic environment.Moreover,pH induced IPN to semi-IPN reversible transition was achieved by selectively hydrolyzing one network to free polymer chains inside the other cross-linked network,endowed the hydrogel with tunable pore structure and mechanical properties which would be useful in tissue engineering and the context of drug delivery.