ABSTRACT
Cardiovascular diseases are a main cause of death worldwide, leading to a growing demand for medical devices to treat this patient group. Central to the engineering of such devices is a good understanding of the biology and physics of cell-surface interactions. In existing blood-contacting devices, such as vascular grafts, the interaction between blood, cells, and material is one of the main limiting factors for their long-term durability. An improved understanding of the material's chemical- and physical properties as well as its structure all play a role in how endothelial cells interact with the material surface. This review provides an overview of how different surface structures influence endothelial cell responses and what is currently known about the underlying mechanisms that guide this behavior. The structures reviewed include decellularized matrices, electrospun fibers, pillars, pits, and grated surfaces.
ABSTRACT
Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER™ technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.