Development of a Janus tissue adhesive hemostatic patch based on hydrophobically-modified Alaska pollock gelatin.

ABSTRACT

Uncontrollable hemorrhage from trauma and open surgery leads to a high percentage of death. Even though some patch-type hemostatic materials have been used in the clinic, sufficient tissue adhesion property and the management of tissue adhesion and anti-adhesion have been the challenges. In this report, we designed Janus tissue adhesive hemostatic patch, consisting of Alaska pollock gelatin (Org-ApGltn) as a support layer and decanoyl group-modified ApGltn (C10-ApGltn) with pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG) as an adhesive layer, named as the C10-ApGltn patch. The C10-ApGltn patch adhered onto blood vessel surface by the activation 4S-PEG and hydrophobic groups in C10-ApGltn through the covalent bond formation and physical interaction. The burst strength of the C10-ApGltn patch was optimized in terms of the degree of substitution, the molecular weight of 4S-PEG, the concentration of C10-ApGltn, and the NHS/NH2 ratio. The optimized C10-ApGltn patch showed significantly higher burst strength with commercially available TachoSil®. The C10-ApGltn patch showed enzymatic degradability in a buffer solution with collagenase. In a rat liver hemorrhage model, the C10-ApGltn patch acted as a sealant on the hemorrhage site and exhibited competitive hemostatic property to TachoSil®.