Microfluidic Synthesis of Biodegradable Polyethylene-Glycol Microspheres for Controlled Delivery of Proteins and DNA Nanoparticles

Abstract

Polymeric microspheres represent an injectable platform for controlling the release of a variety of biologics; microspheres may be combined in a modular fashion to achieve temporal release of two or more biomolecules. Microfluidics offers a versatile platform for synthesizing uniform polymeric microspheres harboring a variety of biologics under relatively mild conditions. Poly(ethylene glycol) (PEG) is a bioinert polymer that can be easily tailored to encapsulate and control the release of biologics. In this study, we report the microfluidic synthesis of biodegradable PEG-based microparticles for controlled release of growth factors or DNA nanoparticles. Simple changes in microfluidic design increased the rate of microparticle formation and controlled the size of the microspheres. Mesh size and degradation rate were controlled by varying the PEG polymer weight percent from 7.5 to 15% (w/v), thus tuning the release of growth factors and DNA nanoparticles, which retained their bioactivity in assays of cell proliferation and DNA transfection, respectively. This platform may provide a useful tool for synthesizing microspheres for use as injectable carriers to achieve coordinated growthfactor or DNA nanoparticle release in therapeutic applications.

Cell-laden microfluidic microgels for tissue regeneration

“…Stable and accurate droplet formation using this method requires the maintenance of a constant pressure difference between the aqueous liquid and oil channels throughout the entire microfluidic fabrication process, which can easily be achieved using syringe pumps. 111 A more robust alternative strategy is to adjust the dimensions of the input microchannels. For instance, increasing the width of the channels enables the formation of droplets with larger diameters.…”

Microfluidic Devices in Fabricating Nano or Micromaterials for Biomedical Applications

“…MDs offer a relatively simple and consistent way for overcoming some of these issues, for synthesizing nanoparticles of uniform size, with better releasing profiles, from different materials such as PLGA, PEG, polycaprolactone (PCL), chitosan, and copolymers . Increased attention has been given to PLGA‐based nanoparticles as nanocarriers of small drugs, peptides, proteins, DNA, or RNA .…”

“…b) Schematic of the addition of bFGF or PBAE/DNA nanoparticle to a PEG precursor solution and subsequent microsphere formation in a droplet‐based MD. Fluorescein isothiocyanate‐conjugated BSA (green) used to visualize protein encapsulation (scale bar: 200 µm) . c) Synthesis of the combinatory Pt(IV) and Docetaxel loaded PLGA nanoparticles using a flow focusing MD .…”

“…Copyright 2018, Elsevier. b) Reproduced with permission . Copyright 2015, American Chemical Society.…”

“…In tissue regeneration and repair, growth factors play a significant role in guiding cell fate, and require well‐designed dosing and timing . PEG, a hydrophilic and biocompatible polymer, can be easily manipulated to encapsulate and control the release of biological reagents.…”