(334cc) Functional Particles for Controlled Release and Stem Cell Engineering

Research Interests: controlled release, drug release, stem cell engineering, nanoparticle formulation, surface modification, polymer chemistry

Stem cells are emerging as new generation of medicine for treating various diseases and tissue defects, as they can secrete a wide range of therapeutic cytokines and growth factors. However, a major obstacle for past utilization is the limited cell secretion activities due to hostile environment or insufficient activation signal at the transplanted site. To this end, we developed a stimuli-responsive particle system, that can be tethered on stem cell surface to provide proximal stimulation and actively release stimuli to enhance the cellular secretion activity. Specifically, we devised a dual binding poly(D, L-lactic-co-glycolic) (PLGA)-based particle system through RGD and hyaluronic polymer modification. We demonstrated that when the particle-tethered stem cells were exposed to shear stress during injection, less than 10% of the particles detached from cell surface. The improved particle retention led to a better stem cell stimulation as demonstrated with a 1.5-fold increase in cellular secretion activity. Further, we designed a catalytic particle system with an enhanced molecular release profile upon reaction with an external stimuli (H₂O₂). The catalytic particle system was assembled by encapsulating MnO₂ and bioactive molecules of interest in PLGA particles. The MnO₂ catalyzed the decomposition of H₂O₂ into oxygen gas, which increased the internal pressure of particles and accelerated the release of the bioactive molecules. We demonstrated that the catalytic particles encapsulated with epigallocatechin gallate can provide cytoprotective effect against reactive oxygen species and subsequently increase the secretion activity by 2.8-fold due the enhanced molecule release effect. Our approach of functional stimuli-responsive particles therefore provides a promising pathway to engineer stem cell surface and control the release of molecules of interest.