Remote induction of hydrogelation in vivo using nanomaterials and electromagnetic fields

Abstract

Injectable hydrogels have been widely used for various biomedical applications, including drug delivery and tissue engineering. Conventionally, temperature or pH responsive materials and self-assemble materials, which spontaneously form hydrogels under physiological conditions, have been utilized as injectable hydrogels. However, such injectable hydrogel systems generally lack of control over the gelation process, and the properties of produced hydrogel are only determined by the pre-set initial compositions. In this thesis, remotely controllable hydrogelation systems were developed to overcome the limitations. To this end, my research has employed biocompatible and tissue-penetrating electromagnetic fields (e.g., near infrared (NIR) light and alternating magnetic field (AMF)), and various nanomaterials (e.g., gold nanorods, superparamagnetic nanoparticles, and graphene oxide), which response to the external electromagnetic field and generate the heat, to finally form PEG hydrogels via radical polymerization with thermal initiator. First, NIR light and gold nanorod (GNR) were used for transdermal hydrogelation and cell delivery. NIR-inducible hydrogelation and control of the shapes and moduli of hydrogels were successfully demonstrated. Additionally, cell encapsulation, and in situ transdermal hydrogelation were successfully demonstrated. Second, AMF and superparamagnetic iron oxide nanoparticles (SPIONs) were used to develop an AMF-inducible hydrogelation system to achieve in situ hydrogelation in deep tissues. Taking advantages of deep-tissue-penetrating ability of AMF, remote induction of hydrogelation in deep sites (>2 cm) was achieved. Additionally, in vivo hydrogelation in biceps femoris muscles of rats was demonstrated. Cell encapsulation of human mesenchymal stem cells via this AMF-induced hydrogelation revealed 80% of cell viability after the encapsulation. Finally, PEGylated graphene oxide (GO-PEG) was used to develop the robust photothermal hydrogelation system that can form hydrogels with various light sources. By irradiation of light with various wavelength (532, 785, and 980 nm), a sufficient increase in the temperature was achieved and the induction of thermal gelation was successfully demonstrated. Remote transdermal gel formation with 785 and 980 nm light was further demonstrated. In conclusion, this thesis demonstrates the remotely inducible hydrogelation systems using various stimuli and nanomaterials for control of hydrogel formation and its properties, and provides a new approach to controllable injectable hydrogels that would benefit various application, including cell delivery and tissue engineering.