Biomimetic sealant based on gelatin and microbial transglutaminase: an initial in vivo investigation

Abstract

The potential of an in situ gel-forming adhesive was examined as a hemostatic surgical sealant. The gel-forming mechanism for this adhesive mimics the last stages of blood coagulation but uses nonblood proteins. Specifically, gelatin is used as the structural protein and a calcium-independent microbial transglutaminase (mTG) is used as the crosslinking enzyme. In vitro burst pressure tests with porcine skin demonstrate that the gelatin-mTG adhesive forms a gel within 30 min under moist conditions and this gel can restrain pressures of 200 mmHg. In vivo tests with a rat liver wound model showed that the gelatin-mTG adhesive achieves complete hemostasis in 2.5 min and the gel (i.e., the biomimetic clot) offers substantial adhesive and cohesive strength. Complete hemostasis was also observed in 2.5 min after the gelatin-mTG adhesive was applied to a briskly bleeding rat femoral artery wound. In a large animal porcine model, a femoral artery wound that resulted in extensive bleeding was sealed in 4 min by (i) clamping the artery for temporary hemostasis, (ii) removing excess blood, and (iii) applying the gelatin-mTG adhesive. Thus, the biomimetic gelatin-mTG adhesive may provide a simple, safe, and cost-effective surgical sealant.