(604b) Magneto-Responsive Bionanocomposite Hydrogels As Injectable Scaffolds for Osteochondral Tissue Regeneration

Osteoarthritis (OA) is a degenerative joint disease that occurs when articular cartilage begins to degrade and can result in severe disability in the lower extremities of the body. Every year, 3.1 million surgeries are done to treat the damage caused by OA^[1], and the annual cost of non-steroidal anti-inflammatory drugs (NSAIDs) approaches $4 billion^[2]. Current treatment options, such as osteochondral tissue grafting, microfracturing, and total knee replacements, are only effective in alleviating symptoms in the short-term and fail to promote the regeneration of fully functional articular cartilage. Thus, more effective therapies are needed to regenerate damaged tissue in a manner that can recreate the stratified, heterogeneous structure of articular cartilage.

Hydrogel scaffolds capable of delivering viable stem cell populations to the cartilage defect and responding to external stimuli, such as a magnetic field, could be used to influence stem cell behavior and guide the reconstruction of a heterogeneous tissue structure. In particular, polymer-based hydrogels made from thermogelling macromers, such as poly(N-isopropylacrylamide) (pNiPAAm), offer promise as in situ forming injectable scaffolds capable of delivering viable stem cell populations in vivo. Furthermore, recent studies have discovered that cytocompatible, hydrophilic polyamidoamine (PAMAM) crosslinkers can counteract pNiPAAmâ??s natural tendency to undergo syneresis post thermogelation,^{[3, 4]} thus enabling these materials to completely fill irregularly-shaped tissue defects and promote integration with surrounding tissue.

The aim of this study was to investigate the efficacy of using a magneto-responsive injectable hydrogel to deliver viable stem cell populations and then stimulate osteochondral tissue regeneration through magnetically-actuated mechanical force. Functional paramagnetic iron (III) oxide Fe₃O₄ nanoparticles were incorporated into a dual-gelling pNiPAAm-based hydrogel with degradable PAMAM-based crosslinking macromers. The physical properties of the hydrogel were assessed by rheology and scanning electron microscopy (SEM), and magnetic properties of the hydrogel were determined by superconducting quantum interference device (SQUID) magnetometry and tangential force measurements. In situ delivery of viable cell populations in the bionanocomposite hydrogels was demonstrated by fluorescent microscopy and biochemical assays. Finally, the effects of magnetic stimulation on stem cell differentiation were investigated.

1. Arthritis Brochure. American Academy of Orthopaedic Surgeons. Available from: www.aaos.org.

2. Van Manen, M.D., J. Nace, and M.A. Mont, Management of primary knee osteoarthritis and indications for total knee arthroplasty for general practitioners. J Am Osteopath Assoc, 2012. 112(11): p. 709-15.

3. Ekenseair, A.K., Boere, K.W.M., Tzouanas, S.N., Vo, T.N, Kasper, K., Mikos, A.G.,, Synthesis and Characterization of Thermally and Chemically Gelling injectable Hydrogels for Tissue Engineering' Biomacromolecules. BioMacromolecules, 2012. 13: p. 1908-1915.

4. Ekenseair, A.K., et al., Structure-property evaluation of thermally and chemically gelling injectable hydrogels for tissue engineering. Biomacromolecules, 2012. 13(9): p. 2821-30.