Heparin-mimicking Reverse Thermal Gel as a Potential Cationic Growth Factor Delivery Vehicle

Growth factor delivery is an important venture in the field of tissue engineering because of its widespread applications and promising therapeutic outcomes. Bolus injection, natural polymers, and synthetic polymers have all been utilized to deliver these specialized proteins to target cells/tissues, but each vehicle category has its own limitations. Bolus injection can deliver growth factors through minimally invasive means, but this method requires multiple injections for therapeutic relevance, has the potential for growth factor influence in non-target tissue, and poses a risk of delivering too high a protein concentration and exerting undesireable effects. Natural polymers are known for their biocompatibility and biodegradability but their batch-to-batch variation can lead to unpredictable growth factor release profiles. Synthetic polymers allow for specific material modification for protein release optimization but can lack biodegradability and biocompatibility possibly require an invasive means of implantation, and introduce harmful or irritating chemicals through in-situ polymerization. General concerns that apply to every delivery vehicle, no matter what type, inclue the necessity for retaining the bioactivity of the growth factor and providing a means through which the protein can be released over an extended time period. To address these limitations, a series of sulfonated reverse thermal gels were investigated for their potential to deliver growth factors. Specifically, the sulfonate groups on the polymer provided a negative charge with which a positively charged growth factor could electrostatically interact--mimicking the natural interaction seen in the body between heparin and cationic growth factors. 1H-NMR showed that the polymer was available for conjugation with the reverse thermal gelling polymer, PNIPAAm, and with the sulfonate groups through a sulfonation reaction. FTIR indicated the presence of sulfonate groups through peak comparison with the original reverse thermal gel before sulfonation. The sulfonated polymers retained their gelation properties after the sulfonation reaction, which confirms that this polymeric solution can be admistered in a minimally invasive manner. Furthermore, the release profiles of sulfonated reverse thermal gels were compared to a non-sulfonated reverse thermal gel using BSA. While the non-sulfonated reverse thermal gel performed similarly to a sulfonated reverse thermal gel, each of the reverse thermal gel contains sulfonate groups that have the potential to mimick heparin and protect positively charged growth factors from proteolytic degradation in the body.