Construction Of Enzyme-Regulated Hydrogels With Their Application As Bioadhesives And Controlled Release Carriers

Enzymes are substances that promote the smooth operation of almost all chemical reactions related to life in living organisms.Therefore,the introduction of enzymes into the design and application of biomaterials is becoming a hot spot.Enzyme-regulated materials such as enzyme-cross-linked hydrogels and enzyme-degraded hydrogels have also attracted increasing attention of researchers.Inspired by the idea that wound damage can expose the enzyme environment,this paper aims to prepare an enzyme-induced cross-linking gel.We first used transglutaminase to catalyze the reaction of amino acid residues in gelatin,and combined with the Schiff base reaction between dextran aldehyde and gelatin to prepare a gelatin-based adhesive with a double network structure.The results showed that the adhesive has an appropriate gel time(～3-6 min)and a low swelling rate.By adjusting the enzyme concentration,the compression strength and bonding strength can reach up to 33.6 k Pa and 25.9 k Pa,which are 4 times and 12 times of the unmodified gelatin gel.In addition,the adhesive had low cytotoxicity and the cell survival rate was about 98% at 72 h,indicating that the enzyme-regulated double-cross-linked network adhesive had potential as tissue adhesive.Subsequently,inspired by the fact that the enzyme environment at the site of human injury changes with time,this paper constructed a hydrogel carrier with timing release function,which can solve the problem of timing delivery of multiple drugs.The main body of the hydrogel was formed by the Michael addition reaction between the enzyme-responsive polypeptide and polyethylene glycol(PEG).The two nanogels encapsulating the model drug are loaded into the hydrogel by physical embedding or chemical substitution.The results showed that the gel showed better timing release properties.In an enzyme-free environment,physically encapsulated drugs are released while chemically coupled drugs are not.In the enzymatic environment,chemically coupled drugs were released rapidly with a high final cumulative release rate(～83%).In addition,the gel has good physical properties and biocompatibility,such as suitable gel time(～4-5 min),low equilibrium swelling rate,good mechanical strength(～34.5 k Pa)and low cytotoxicity.