Injectable, magnetoresponsive hydrogels for in situ physical actuation of osteochondral tissue regeneration

Abstract

Event Abstract Back to Event Injectable, magnetoresponsive hydrogels for in situ physical actuation of osteochondral tissue regeneration Adedokun Adedoyin1 and Adam K. Ekenseair1 1 Northeastern University, Chemical Engineering, United States Introduction: Every year 3.1 million surgeries are performed to treat bone and cartilage damage caused by Osteoarthritis (OA), however, many of these procedures fail to restore full functionality and structure[1]. In particular, articular cartilage has proven challenging to heal due to its avascular and heterogeneous structure. Recent efforts have sought to move away from implantable scaffolds and develop novel, minimally invasive therapies capable of forming in situ and promoting close contact with existing tissue to enhance tissue repair. In particular, thermogelling macromers (TGM) that have a lower critical solution temperature (LCST) close to body temperature, such as poly(N-isopropylacrylamide) (PNiPAAm), are promising candidates capable of delivering viable encapsulated cells[2]. The next grand challenge in the development of injectable scaffolds is to create responsive materials that can be externally directed in a spatiotemporal manner to guide the regeneration of a heterogeneous tissue defect. This paper reports on the development of injectable, dual-gelling bionanocomposite hydrogels composed of PNiPAAm-based TGMs, degradable polyamidoamine (PAMAM) crosslinkers, and functional iron oxide (Fe3O4) nanoparticles capable of responding to an external magnetic field in order to stimulate cell activity and control the regenerative process in situ. Materials and Methods: PNiPAAm was copolymerized with glycidyl methacrylate (GMA) and PAMAM crosslinkers were created from piperazine and methylene bisacrylamide following previous synthesis procedures[3]. 50 nm and 500 nm amine-functionalized Fe3O4 particles were purchased from Ocean Nanotech, LLC. Injectable solutions were mixed and injected into a Teflon mold at 37ºC to form magnetic hydrogels. Polymer molecular weight was determined by GPC; LCST by differential scanning calorimetry (DSC); and Young’s Modulus by rheology. The magnetic properties of the hydrogel were determined by SQUID and tangential force measurements. The viability, activity and differentiation of mesenchymal stem cells were evaluated in vitro under varied magnetically-actuated stimulation regimes. Results and Discussion: The incorporation of nanoparticles into the injectable hydrogel system did not alter the LCST or thermogelation process. SQUID analysis demonstrated that the nanocomposite hydrogels exhibit paramagnetic behavior under strong magnetic fields, and tangential force measurements were made to evaluate the efficacy of utilizing an externally-controlled magnetic field to mechanically stimulate encapsulated cells (Fig, 1 & 2). Finally, the in situ delivery of viable cell populations encapsulated in the bionanocomposite hydrogel was demonstrated (Fig. 2 inset), and the effects of magnetic stimulation were elucidated. Conclusions: An injectable, bionanocomposite hydrogel scaffold responsive to an external magnetic field was developed and demonstrated potential for guided regeneration of osteochondral tissue defects. Robert Egan at Northeastern University; Dr. Abigail Koppes at Northeastern University; Dr. Sridhar at Northeastern University; Northeastern University's Tier 1 Grant Program; Chemical Engineering Department Northeastern University