Nanomaterial-containing functional hydrogel biomaterials for various tissue engineering applications

Abstract

Hydrogels have been extensively used in various fields including biomaterials and tissue engineering because of their excellent hydrophilicity, similarity with extracellular matrix, and biocompatibility. However, conventional hydrogels have several limitations for tissue engineering applications, such as low efficiency in tissue regeneration due to insufficient mechanical properties, biological activity, and anti-oxidizing properties. In order to address such limitations, chemical modification, copolymerization, or incorporation of nanomaterials have been widely attempted. Especially, incorporation of nanomaterials into hydrogels can make the hydrogels show additional functional properties by additionally providing a variety of characteristics of a nanomaterial together with the unique properties of the hydrogel. In this thesis, various functional hydrogels incorporated with various nanomaterials were developed to improve the properties of hydrogels for tissue engineering. Specifically, I developed nanoparticle-containing hydrogels (i) for cell/drug delivery presenting anti-oxidizing activity with graphene oxide (GO) for various tissue regeneration and (ii) for a novel bio-ink containing GO or BMP-2-loaded poly(lactic-co-glycolic acid) (PLGA) for mesenchymal stem cells (MSCs) printing for bone differentiation. First, MSCs were encapsulated in a micro-sized hydrogel using GO and alginate to protect the encapsulated cells from the oxidative stress environment that occurs after myocardial infarction and improve heart regeneration efficiency. The anti-oxidizing activity of the GO in MSC-containing microgels could be improved through a mild chemical reduction. Intracardial injection of the MSCs encapsulated in reduced GO/alginate microcapsules to the infarcted rat hearts led to significant reduction of the fibrosis of the ventricle and the improvement of heart functions. Second, reactive oxygen species (ROS)-scavenging and ROS-inducible drug delivery system was developed for muscle regeneration using hyaluronic acid (HA) and GO hydrogel microparticles. The anti-oxidizing activity and drug adsorption capacity of the hydrogel were significantly improved by GO incorporation and chemical reduction of the HA/GO microparticles. Accelerated drug release from the reduced HA/GO microgels was observed under oxidative stress environments. Third, I developed a bio-ink for 3D MSC printing and osteogenic differentiation using GO and alginate. GO-incorporated alginate bioinks exhibited the appropriated mechanical properties for 3D printing, excellent stability of the printed scaffolds, and highly improved osteogenic induction. Finally, I prepared BMP-2 loaded PLGA nanoparticles and formulated them with alginate to develop the bioinks for MSC printing and osteogenic induction. The incorporation of BMP-2 loaded PLGA nanoparticles not only improved the mechanical properties of the alginate bioink, but also enhanced biological activities resulting from sustained release of BMP-2 and mechano-transduction for the osteogenesis. In conclusion, this thesis has elaborated to develop novel biomaterial systems that endow new properties to hydrogels by incorporation of various functional nanomaterials, and thus provide a novel approach to create and employ functional hydrogels for tissue regeneration.