Improved hydration property of tissue adhesive/hemostatic microparticle based on hydrophobically-modified Alaska pollock gelatin.

The management of bleeding is an important aspect of endoscopic surgery to avoid excessive blood loss and minimize pain. In clinical settings, sprayable hemostatic particles are used for their easy delivery, adaptability to irregular shapes, and rapid hydration. However, conventional hemostatic particles present challenges associated with tissue adhesion. In a previous study, we reported tissue adhesive microparticles (C10-sa-MPs) derived from Alaska pollock gelatin modified with decyl groups (C10-sa-ApGltn) using secondary amines as linkages. The C10-sa-MPs adhere to soft tissues through a hydration mechanism. However, their application as a hemostatic agent was limited by their long hydration times, attributed to their high hydrophobicity. In this study, we present a new type microparticle, C10-am-MPs, synthesized by incorporating decanoyl group modifications into ApGltn (C10-am-ApGltn), using amide bonds as linkages. C10-am-MPs exhibited enhanced hydration characteristics compared to C10-sa-MPs, attributed to superior water absorption facilitated by amide bonds rather than secondary amines. Furthermore, C10-am-MPs demonstrated comparable tissue adhesion properties and underwater adhesion stability to C10-sa-MPs. Notably, C10-am-MPs exhibited accelerated blood coagulation in vitro compared to C10-sa-MPs. The application of C10-am-MPs in an in vivo rat liver hemorrhage model resulted in a hemostatic effect comparable to a commercially available hemostatic particle. These findings highlight the potential utility of C10-am-MPs as an effective hemostatic agent for endoscopic procedures and surgical interventions.

Effect of particle size on the tissue adhesion and particle floatation of a colloidal wound dressing for endoscopic treatments.

Endoscopic submucosal dissection (ESD) is a minimally invasive technique that is widely used to remove gastrointestinal tumors. However, because the walls of the duodenum and large intestine are thin, perforation can easily occur after ESD. We have previously reported that alkyl group-modified Alaska pollock gelatin-based microparticles (C10Ps) formed a colloidal gel that could adhere to defects and close perforations, driven by hydrophobic interactions. The present study focused on the effect of particle size on the colloidal gel properties and the floatation of C10Ps in the air in the delivery of C10Ps. We prepared C10Ps with different particle sizes from 0.1 to 100 µm. The storage modulus and adhesion strength of the C10P colloidal gel increased with decreasing particle size. All the C10Ps formed a colloidal gel layer on duodenum tissue after being sprayed from an endoscopic device. The underwater stability and burst strength of C10Ps with a particle size of 0.1 and 1 µm were higher than for larger C10Ps. Floating of the small-sized C10Ps in the air was observed. The results indicated that C10Ps with a size of 1 µm had suitable properties for use in endoscopic treatments. STATEMENT OF SIGNIFICANCE: We previously reported tissue adhesive microparticles as a spray-deliverable wound dressing in gastrointestinal tissues. However, their functions depending on particle size have not yet been clarified. In the present study, we prepared decyl group-modified Alaska pollock gelatin nano and microparticles (C10Ps) with different particle sizes from 0.1 to 100 µm and evaluated the effect of particle size on the colloidal gel properties (rheological property, underwater stability and perforation-closing ability) and the floatation of C10Ps in the air in the delivery of C10Ps.

Robust closure of post-endoscopic submucosal dissection perforation by microparticle-based wound dressing.

Endoscopic submucosal dissection (ESD) has been used as a minimally invasive cancer treatment for early-stage gastrointestinal cancer. However, cancer dissection in thin tissues, such as the duodenum and large intestine, often cause post-ESD and delayed perforation, which elicit severe complications. In this study, we report a microparticle-based wound dressing with hydrophobically-modified gelatin that can close the perforation after ESD. Hydrophobized microparticles were prepared using a coacervation method in a water/ethanol mixed solvent. The optimized alkyl chain length and degree of substitution of hydrophobic groups improved the mechanical strength of the hydrogel formed by hydration and fusion of the microparticles. The hydrogels formed on tissue defects revealed higher burst strength in ex vitro perforation models using duodenum, large intestine, and stomach under wet conditions compared with hydrogels without hydrophobic modification. The particle fusion was determined to be a crucial step to yield a high burst strength. An in vivo degradability evaluation showed that microparticle hydrogels subcutaneously implanted in rats degraded within 14 days. The microparticle wound dressing is expected to be applicable to post-ESD perforation and prevent delayed perforation.