Immune-Modulating Scaffolds in Drug Delivery and Bone Tissue Engineering

Authors: 
Nguyen, T., Columbia University
My project involves the investigation of nanoparticles adhered on 3D printed scaffolds and their application in cell drug delivery for tissue engineering. The development and use of nanoparticles in biology is a new and practical way to explore the properties associated with these polymers and by taking advantage of their small size and stability, practical models can be used in future cell delivery techniques for drug delivery. This is an important endeavor because many drugs fail because its content were not appropriately released and therefore the effects aren’t as potent. Our goal will be to enhance the surface coverage of Heparin-Poly-L-Lysine (Hep-PLL) nanoparticles (NPs) immobilized on 3D printed Poly Lactic-co-Glycolic Acid (PLGA) scaffolds. We will be testing coating conditions as well as different scaffold materials. Once we find an optimum condition for high surface coverage we will move on to include immune-modulating cytokines (i.e. the drug) into the nanoparticles and test tissue growth. It has been shown that anti-inflammatory cytokines can reduce inflammation in osteoblasts (bone cells) and promote tissue regeneration in sites of injury, therefore anti-flammatory cytokines such as IL-4 and IL-10 are ideal candidates as the drug.

In our current model, we use Layer-by-Layer (LBL) assembly, which characterizes the assembly of oppositely-charged polymers on a substrate to bind the protein of interest, in this case, it is Hep-PLL NPs. Of particular interest here is its charge, biocompatibility, and biodegradability. The solvent, nanoparticle, and scaffold are chosen so that all are alternating in charge and therefore the LBL model will be successful. Prior to incorporation on the scaffold, solutions of the nanoparticles at different compositions have been carried out to determine stability. To determine the stability and size of the nanoparticles, the Malvern Zetasizer was used. This equipment measures the size and zeta potential, or surface charge of the nanoparticle, and certain levels of charge indicate a stable equilibrium. Once included on the scaffold, Scanning Electron Microscopy (SEM) can be used to image the surface of the scaffold and determine surface coverage. Thereafter, the cytokines can be added to the nanoparticles and delivered into cell cultures on the PLGA-scaffold. Inflammatory markers of each cytokine can determine the effects of the immobilized NP-cytokine drug delivery system in vitro.