The degradation of articular cartilage in connective joints due to Osteoarthritis (OA) leads to swelling, stiffness and severe pain and is the leading cause of disability in the lower extremities among the elderly in the United States. These osteochondral injuries have proven challenging to heal due to the tissue’s complex, avascular structure. Current treatment options for OA, such as arthroscopic lavage, microfracturing, and osteochondral grafting, provide short term symptomatic relief; however all of the aforementioned procedures require invasive open surgery with associated risks, including infection and donor-site morbidity. Furthermore, these treatment options do not restore full mechanical functionality and have low long-term success rates. Thus, it has become a prime objective in tissue engineering to discover novel, minimally-invasive treatment options with spatiotemporal control to regenerate osteochondral tissue.
Thermogelling macromers (TGMs), such as poly(N-isopropylacrylamide) (pNiPAAm), that undergo a lower critical solution temperature (LCST) close to body temperature, can be used as injectable in situ scaffolds for tissue repair. Furthermore, it has been shown that pNiPAAm is capable of delivering viable encapsulated cell populations in vivo, and recent studies have discovered that cytocompatible, hydrophilic polyamidoamine (PAMAM) polymers can be used as chemical crosslinkers to counteract pNiPAAm’s natural tendency to undergo syneresis during thermogelation. The next grand challenge in the development of injectable scaffolds is to endow them with spatiotemporally-controlled signaling in order to influence cell behavior and guide the reconstruction of a heterogeneous tissue.
This paper reports on the incorporation of functional paramagnetic iron (III) oxide (Fe3O4) nanoparticles into an injectable, thermally and chemically dual-gelling pNiPAAm-based hydrogel with degradable PAMAM-based crosslinking macromers. This novel injectable bionanocomposite hydrogel is responsive to a magnetic field and provides a non-invasive approach to stimulate cell activity and the regenerative process in situ. The efficacy of in situ hydrogel formation, dimensional stability, mechanical properties, reaction kinetics, tangential force potential, cytocompatibility, and cell encapsulation were evaluated, and the effects of polymer and nanoparticle chemistry and loading were investigated.