Tetra-armed PEG-based rapid high-adhesion, antibacterial and biodegradable pre-clinical bioadhesives for preventing pancreas leakage

Abstract

Pancreatic leakage is severe and life-threatening when happening pancreatitis or conducting pancreatectomy on patients, which easily induces bleeding, infection and even death. Commercial tissue adhesives cannot meet the demands for pancreatic leakage sealing due to the weak adhesiveness, potential toxicity and inability to degrade. Few reports have been feasibly paid attention to pancreas sealants due to the complicated conditions such as enzymatic microenvironments, mechanical dynamics and pre-infections. Herein, we prepared a rapid high-adhesion, antibacterial, biodegradable and injectable bioadhesive based on the FDA-approved polyethylene glycol to seal the pancreatic leakage for clinical translations and commercial applications. The tetra-armed poly(ethylene glycol) succinimidyl glutarate (PEG-SG), tetra-armed poly(ethylene glycol) amine (PEG-NH2) and tannic acid (TA) were integrated to rapidly form the adhesive hydrogel (gelling time < 5 seconds) for convenient operations, while this bioadhesive achieved tough tissue adhesion (∼ 30 kPa), robust antibacterial activity (∼ 95% efficiency) and biocompatibility, revealing the excellent performances for pancreatic wound closure. In the established pre-clinical pancreatectomy using Bama miniature pig model, the bioadhesive presented efficient outcomes on pancreatic leakage, and this indicated the promising feasibility of the bioadhesive for clinical trials and translations.

Keywords

• Tissue adhesive
• Tissue sealing
• PEG
• Antibacterial
• Pancreatic closure