Abstract
Anastomotic leakage remains a serious complication in gastrointestinal surgery, with unsatisfactory improvement in incidence over recent decades. Conventional sealants, such as fibrin glue, require intraoperative mixing and offer limited ease of handling. Here, we report a ready-to-use, thixotropic hydrogel that is injectable during application and solidifies upon contact with tissue. The hydrogel consists of self-assembled nanofibers of an elastin-like polypeptide crosslinked with oxidized dextran (OD). Rheological step-strain measurements demonstrated reversible sol–gel transitions and shear-responsive behavior, with the most highly oxidized formulation exhibiting the greatest recovery of the storage modulus (44.2%) after high strain. This formulation also showed adhesive strength comparable to fibrin glue in lap-shear tests and a burst pressure (14.8 ± 3.6 kPa) comparable to that of fibrin glue (15.4 ± 4.8 kPa) on porcine small intestine. In vivo experiments in mice demonstrated that the hydrogel remained localized at the injection site up to one week after intraperitoneal administration, indicating favorable physiological stability. Histological analysis revealed only mild serosal thickening without severe inflammation. These findings suggest that this shear-thinning, self-healing hydrogel may serve as a practical and effective sealant for surgical reinforcement and could contribute to reducing the risk of anastomotic leakage in gastrointestinal surgery.
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Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers 23K18312 and 23H04934, the MEXT Program: Data Creation and Utilization-Type Material Research and Development Project (Grant Number JPMXP1122714694), and the MEXT Program: Advanced Research Infrastructure for Materials and Nanotechnology in Japan (ARIM, Grant Number JPMXP1222NU0266). We thank Yoshiharu Sawada (Nagoya University) for assistance in 1H NMR measurements.
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Y.A., M.K., and A.S.-N. conceived and designed the study. Y.A., under the supervision of K.S., C.O., and A.S.-N., performed material preparation, structural analysis, rheological measurements, lap shear tests, and drafted the manuscript. Y.N. was responsible for material preparation and burst pressure measurements. T.S. and K.A. conducted the animal experiments. A.S.-N. wrote the manuscript. M.K., K.S., and C.O. reviewed and edited the manuscript. All authors contributed to the finalization of the manuscript.
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Aoyama, Y., Nakano, Y., Shinozuka, T. et al. Injectable thixotropic hydrogel composed of elastin-like polypeptide and oxidized dextran for anastomotic support. NPG Asia Mater (2026). https://doi.org/10.1038/s41427-026-00646-7
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DOI: https://doi.org/10.1038/s41427-026-00646-7
