ChE PhD Dissertation Proposal Defense by Adedokun Adediji Adedoyin
Advisor: Dr. Adam K. Ekenseair
The restoration of cartilage tissue damaged by osteoarthritis (OA) has been a primary target in the field of tissue engineering due to the tissue’s inherent lack of functional regeneration. Recent research has sought to enable the rapid regeneration of osteochondral tissue defects through a combination of scaffolds, cells, and biomolecular signals. In particular, the scaffold design plays a critical role in guiding the regeneration of a complex, heterogeneous tissue structure in vivo. The major focus thus far has been in constructing implantable scaffolds that have similar physical and mechanical properties to that of native cartilage. However, the use of implantable scaffolds causes many challenges as they require open surgery, and defects of irregular shapes are problematic to repair. Moreover, implantable scaffolds fail to promote good integration with the host tissue as a fibrous capsule is generally formed around the scaffold. As a result of the multiple drawbacks of using implantable scaffolds, it has become prominent that researchers develop more effective, and minimally-invasive methods to restore damaged cartilage tissue.
Recent efforts have looked into using injectable scaffolds to repair cartilage defects because they are minimally invasive, can conform to complex tissue defects, and also promote good integration with the host tissue. Thermogelling polymers, that have a lower critical solution temperature (LCST) close to body temperature, can be used as injectable, hydrogel scaffolds for osteochondral tissue regeneration applications as they are capable of delivering and maintaining viable stem cell populations. However, the next grand challenge in the development of injectable scaffolds is to endow them with spatiotemporally-controlled signaling to guide the regenerative process in situ.
The purpose of this research is to investigate the feasibility of using an injectable, magneto-responsive hydrogel system to deliver viable stem cell populations into an osteochondral tissue defect, and guide the regeneration of damaged cartilage tissue via an external magnetic field in vivo. The magneto-responsive hydrogel will be made by combining a thermogelling polymer based on poly(N-isopropylacrylamide), degradable polyamidoamine-based crosslinking macromers, and functional iron (III) oxide (Fe3O4) nanoparticles capable of responding to a magnetic field. The physical properties of the hydrogels and cellular responses to changes in hydrogel shape/volume (caused by variations in the external magnetic field) will be investigated. Biochemical assays and histological staining techniques will be implemented to verify the differentiation of stem cells to a chondrogenic lineage, and the biocompatibility of these bionanocomposite hydrogel scaffolds will be tested in vivo in a small animal model. Furthermore, the construction of a heterogeneous, multi-layered scaffold from an injectable hydrogel formulation will be examined. We hope that the findings of our research will initiate further interest in using stimuli-responsive materials to regenerate damaged tissue, and encourage other bioengineers to look into other minimally-invasive methods to repair damaged cartilage.