Nanogel-Based Drug Delivery: Tailoring BMP-2 Release for Bone Regeneration

Abstract

Critical sized bone defects (CSBDs) do not heal spontaneously, requiring medical intervention. Continuous bone morphogenetic protein-2 (BMP-2) delivery to an injured site is necessary for CSBD regeneration. However, direct BMP-2 delivery is ineffective due to the protein’s short half-life. Nanogels can be used to encapsulate and sustain bioactive BMP-2 release for long time periods. In this study, novel BMP-2 loaded nanogels composed of thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) and hydrolytically degradable dextran-poly(lactate (PLA)-2-hydroxyethyl-methacrylate) or dextran-poly(caprolactone (PCL)-2-hydroxyethyl-methacrylate) macromer were synthesized using emulsion polymerization. Macromers containing PCL or PLA with different degrees of substitution and degree of polymerization (DP/DS), 6/3.8, 6/2.49, 8/3.73 and 8/4.7 were used during synthesis. All nanogels load BMP-2 with approximately 90% encapsulation efficiencies, and range in hydrodynamic diameter between 80 and 196 nm with increasing DP and DS. In vitro BMP-2 release from the nanogels were carried out for 18 days, and released BMP-2 was quantified by ELISA. Among nanogels sustain releasing BMP-2, PCL macromer nanogels with a DP/DS of 6/3.8 had the slowest overall cumulative BMP-2 release, while BMP-2-loaded nanogels containing PLA macromers showed the slowest release with increasing DP and/or DS. Nanogel vehicle cytotoxicity to dental pulp stem cells (DPSCs) was tested using MTT and showed that nanogels were not cytotoxic to DPSCs at concentrations up to 5mg/mL. Overall, the nanogel systems demonstrate a promising approach to sustain BMP-2 release with tailored release kinetics for CSBD regeneration.