Smart Thermo-responsive Lanthanide-based Supramolecular Biocomposite Hydrogels for Biomedical Applications

Uncontrollable bleeding poses considerable fatality risks since relatively slow natural hemostasis of the human body fails to timely address large-area/irregularly-shaped external injuries, as well as internal injuries of non-compressibility/unknown location, with large volumes of blood loss. Current emergency antibleeding handlings include either compression with gauze as pre-hospital first-aid care or significant blood transfusion to passively compensate for the blood loss, which are far from ideal. The demand for external hemostatic methods cannot be overstated.

To this end, novel hemostatic agents and biomaterials based on various antibleeding mechanisms have therefore been developed to provide alternative options to save human lives, but no one stands out as the best many-sided choice and most of them are without detailed enough biomedical studying. Two challenges still remain there that: such new hemostatic agents and materials (i) are used without considering the subsequent tissue repairing issues, and (ii) fail to afford real-time direct imaging of any anastomotic leakage or internal bleeding which is difficult to detect. To address them simultaneously, we hypothesize that incorporating biocompatible supramolecular collagen hydrogel (facilitating later-stage wound healing) and self-referencing highly sensitive thermal imaging property (due to subtle temperature difference around the leakage bleeding sites) into the future hemostatic biomaterials design can be a creative and promising resolution.

In this project, we aim to develop new “all-round” multifunctional hemostatic biomaterials by conflating bioregenerative temperature-sensitive collagen aggregate hydrogels and biocompatible temperature-sensitive bislanthanide complexes for rapid tissue repairing and precise thermal imaging. To substantiate our proposal, we had conducted FOUR proof-of-concept preliminary experiments: (1) we had designed, synthesized and characterized a novel biocompatible and biodegradable collagen-based mucomimetic poloxamer 407 (F-107), TG-Gel-Ag-col, containing polyvinylpyrrolidone (PVP) and silver nanoparticles (AgNPs), which illustrated thermo-reverse gelation, good elasticity and antibacterial/ bacteriostatic properties; (2) TG-Gel-Ag-col had been confirmed in vitro and in vivo to have prominent hemostatic performances, i.e. within 1 min at physiological temperature to stop bleeding; (3) TG-Gel-Ag-col had demonstrated a much better wound healing rate in vivo with more expression of the three growth factors bFGF, VEGF, and PDGF; (4) we had prepared the lanthanide polymer with promising emission enhancement once cross-linked with TG-Gel-Ag-col. Through uniquely long-lived fingerprint lanthanide luminescence tracing, real-time monitoring of the hemostatic biomaterials in vitro/in vivo in terms of pharmacokinetics, biodistribution, etc. in addition to traditional biochemical means would first be feasible.