Development and Characterization of Hyaluronic Acid Microgels for Neural Regeneration Applications

Abstract

Delivery of therapeutic compounds via biomaterial systems has shown promise for tissue regeneration following central nervous system (CNS) injuries. Stromal cell-derived factor-1a (SDF-1a) modulates progenitor cell recruitment to neural injury sites and may contribute to neural repair. However, SDF-1a has a short half-life and requires a delivery system to both protect and sustain its release. Here, we sought to develop a drug delivery platform capable of releasing SDF-1a in a controlled fashion while minimizing inflammation. We used modified hyaluronic acid and microfluidics to generate monodisperse microgels. Characterization of these microgels included size, tunability, degradation, and controlled release properties. Finally, we delivered SDF-1a-loaded microgels to a mouse model of traumatic brain injury at 7 days post-injury and assessed their impact on neural progenitor cell recruitment and astrogliosis. The microfluidic system generated highly monodisperse microgels that successfully encapsulated a matrix metalloproteinase (MMP)-cleavable SDF-1a peptide and retained sensitivity to collagenase. Following intracortical injections, the microgels did not exacerbate the astrocytic response compared to saline injections; no significant difference was observed in neural progenitor cell migration patterns compared to controls. Therefore, we developed a biocompatible microgel system that is highly adaptable for biological delivery and may be utilized in brain/neural applications without exacerbating neuroinflammation.