(7a) Evaluation of Thermosensitive Microparticle-Hydrogel Composite for Protein Delivery

Over the past several years, in situ-forming polymer systems have attracted interest due to their minimally invasive implantation and ability to a form space-filling solid within tissue. Thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm) is one such system. Below its lower critical solution temperature (LCST), typically around 32°C, the polymer forms a miscible solution with water. Above the LCST, it becomes hydrophobic, so the polymer and water separate, forming a compact gel. We are investigating novel injectable materials composed of PNIPAAm lightly crosslinked with poly(ethylene glycol) (PEG) 4600 and 8000 g/mol as multi-functional scaffolds for repair of the degenerated intervertebral disc. Because of the injectable nature of this PNIPAAm-based system, it can be used to simultaneously deliver molecular and cellular factors necessary for tissue regeneration. In this work, the potential of these copolymers to serve as prolonged release vehicles for therapeutic proteins is investigated.

Poly(lactic-co-glycolic) acid particles loaded with the model protein lysozyme, with an average size of 1.7651 µm and a protein loading efficiency of 51.24% were combined with both PNIPAAm-PEG (4600 and 8000 g/mol) to form a composite system. The composite dampened the typical burst effect of protein release in the first 72 hours of a 28 day release study when compared to freely suspended microparticles. The effect of PEG molecular weight on protein release from the composite was shown to be negligible. Compressive testing was also conducted and it was determined through that the presence of microparticles did not significantly affect the modulus values of the hydrogels. Currently, we are investigating the morphological characteristics of the hydrogels to determine changes in the porosity and pore interconnectivity as the embedded particles degrade. The results of this study demonstrate PNIPAAm-PEG copolymers have the potential to serve as multi-functional scaffolds for intervertebral disc tissue regeneration.