Remote induction of in situ hydrogelation in a deep tissue, using an alternating magnetic field and superparamagnetic nanoparticles

Abstract

In situ hydrogelation systems, such as transdermal polymerization, allow for external control over the gelation processes in a minimally invasive way. Recently, a novel system consisting of near-infrared (NIR) light and plasmonic nanomaterials was demonstrated to cause in vivo transdermal gelation. However, NIR light is not sufficient for gelation induction in deep tissues owing to its limited penetration into tissues. To overcome this problem, here we developed an alternating magnetic field (AMF)-inducible hydrogelation system with superparamagnetic iron oxide nanoparticles (SPIONs), by which a deep-tissue–penetrating AMF can induce heat generation in the SPIONs and temperature elevation (≥ 43 °C), leading to initiation of thermal polymerization of poly(ethylene glycol) diacrylate. The feasibility of our AMF-inducible hydrogelation was successfully demonstrated using thick porcine muscle tissues (> 2 cm), whereas the NIR light–based hydrogelation system could induce gelation only in tissues thinner than several millimeters. Cell viability assays indicated cytocompatibility of the AMF-inducible hydrogelation for cell encapsulation and delivery. In vivo hydrogelation in rat muscle tissues further validated in situ hydrogelation in deep muscle tissues of a living animal. This AMF-inducible hydrogelation system may overcome the conventional problems of depth limitation and should extend the applicable area of on-demand injectable hydrogel systems for tissue engineering and drug delivery applications.