Controlled Release Hydrogels for Multiphase Delivery of Growth Factors for Bone Regeneration

A persistent issue in the practice of bone tissue engineering is the controlled and extended release of growth factors at the site of injury. Currently, growth factors are administered via collagen sponges which cause rapid release of growth factors over a short period of time. This leads to over-administration of the drug and side effects such as cancer. As an alternative, hydrogels are widely studied in the field of drug delivery due to their tunability and similarity to the extracellular matrix. In this study, we present a novel method of delivery to overcome these obstacles through the use of hydrogel nanoparticles that can be tuned to release a drug across different timescales. These nanoparticles are conjugated to a scaffold to localize the nanoparticles and further tune the drug release rate. This study explores strategies to synthesize and characterize nanoparticles for multi-phase controlled release delivery.

Hydrogel nanoparticles were synthesized by inverse emulsion polymerization of 2-hydroxyethyl methacrylate and methacrylic acid and crosslinked with varying amounts of tetraethylene glycol dimethacrylate. The particles were purified using acetone precipitation and dialyzed. Particle composition was confirmed with Fourier Transform Infrared Spectroscopy and particle swelling was analyzed with dynamic light scattering to measure particle size. Electrophoretic light scattering was also used to measure the zeta potential of the particles. Methacrylic acid incorporation was verified using potentiometric titration. Protein loading into the particles over time was measured using the Micro BCA protein assay for three model proteins of varying molecular weights. Further studies are in progress to evaluate protein release, cytocompatibility, and the ability to release multiple proteins at variable rates from a single scaffold. Ultimately, this work presents a promising strategy for the delivery of multiple proteins for bone tissue engineering applications.