In this study, chemically crosslinked gelatin microgels were incorporated into dopamine-modified poly (ethylene glycol) (PEGDM) adhesive to form composite bioadhesive with simultaneously improved adhesive property and bioactivity. Gelatin microgel, with an average diameter of 53.6±14.2μm, was prepared with water in oil emulsification method and chemically crosslinked with 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Gelatin microgels were incorporated into PEGDM adhesive precursor solution at 1.5wt%, 3.75wt% and 7.5wt%. The cure time of adhesive reduced from 54 seconds to 37 seconds with increasing gelatin microgel content. Additionally, the incorporation of the gelatin microgel also increased the crosslinking density of the adhesive network as indicated by the reduced equilibrium water content and increased elastic modulus based on compression testing. The compliance of adhesive was not compromised with the increased crosslinking density, as the failure strain showed no significant decrease from the compression testing result. Results from oscillator rheometry indicated that both the storage and loss moduli of the adhesive increased with increasing microgel content, which suggested that the microgels increased both chemical and physical crosslinks in the adhesive architecture. The increased physical crosslink indicated increased energy dissipation ability of the adhesive. Lap shear adhesive test demonstrated that the addition of gelatin microgel enhanced the adhesive property of adhesive. The adhesive property was increased 1.5-2 fold after the addition of gelatin microgel. In the in vitro degradation test, samples of different formulation groups degraded gradually under a similar rate after soaked in the phosphate buffer solution (pH=7.4) and incubated at 37°C. After 8 weeks samples were completely degraded. The in vitro cell viability was tested with L929 mouse fibroblast and the results showed no cytotoxicity in each test formulation. The in vitro cell attachment experiment revealed an enhanced cell attachment and spreading of primary rat dermal fibroblast on gelatin microgel containing PEGDM adhesive compared to the adhesive without gelatin microgel. The results of rat subcutaneous implantation revealed higher cell recruitment and collagen deposition compared with control adhesive group which has no gelatin microgel in structure. Cell infiltration was found in the pocket structure formed by the degradation of gelatin microgel. In conclusion, the incorporation of gelatin microgel presents a simple method to simultaneously enhance the adhesive property and bioactivity of bioadhesive
