Acrylic Acid Modified Poly-ethylene Glycol Microparticles for Affinity-Based release of Insulin-Like Growth Factor-1 in Neural Applications

Sustained release of bioactive molecules via affinity-based interactions presents a promising approach for controlled delivery of growth factors. Insulin-like growth factor-1 (IGF-1) has gained increased attention due to its ability to promote axonal growth in the central nervous system. In this work, we aimed to evaluate the effect of IGF-1 delivery from polyethylene-glycol diacrylate (PEG-DA) microparticles using affinity-based sustained release on neurons. We developed PEG-DA-based microparticles with varying levels of acrylic acid (AA) as a comonomer to tune their overall charge. The particles were synthesized via precipitation polymerization under UV light, yielding microparticles (MPs) with a relatively low polydispersity index. IGF-1 was incubated with the PEG-DA particles overnight, and formulations with a higher AA content resulted in higher loading efficiency and slower release rates over 4 weeks, suggesting the presence of binding interactions between the positively charged IGF-1 and negatively charged particles containing AA. The released IGF-1 was tested in dorsal root ganglion (DRG) neurite outgrowth assay and found to retain its biological activity for up to two weeks after encapsulation. Furthermore, the trophic effect of IGF-1 was tested with stem cell-derived V2a interneurons and found to have a synergistic effect when combined with neurotrophin-3 (NT3). To assess the potential of a combinatorial approach, IGF-1-releasing MPs were encapsulated within a hyaluronic acid (HA) hydrogel and showed promise as a dual delivery system. Overall, the PEG-DA MPs developed herein deliver bioactive IGF-1 for a period of weeks and hold potential to enable axonal growth of injured neurons via sustained release.