An in vitro tissue model for screening sustained release of phosphate-based therapeutic attenuation of pathogen-induced proteolytic matrix degradation

Abstract

Tissue response to intestinal injury or disease releases pro-inflammatory host stress signals triggering microbial shift to pathogenic phenotypes.

Characterizing the Molecular Architecture of Hydrogels and Crosslinked Polymer Networks beyond Flory–Rehner—I. Theory

“…Since the first synthetic hydrogel made by Wichterle and Lim in 1954, the growth of hydrogel technologies has progressed in a variety of fields, as materials for food additives, pharmaceuticals, and biomaterials, including contact lenses, wound dressings, , biomedical implants, scaffolds for tissue engineering, − and controlled drug delivery devices. − Our research group has focused on the production of poly­(ethylene glycol) (PEG)-based hydrogel scaffolds for vascularization of engineered tissues and nanoparticles for sustained release of therapeutic molecules for targeted drug delivery, − enabled by the use of the bifunctional crosslinking macromer poly­(ethylene glycol) diacrylate (PEGDA) within the hydrogel precursor formulation. More specifically, our recent research efforts in drug delivery have focused on the controlled release of biotherapeutics of varying size and conformation that show promise as novel treatments in tissue regeneration, gene delivery, and vaccine development.…”

The surrogate scaffold method for quantifying molecular release kinetics from drug delivery systems

“…Our group has used this class of NPs in various studies for the prevention of bacterial transition to virulence that could lead to sepsis, suppression of biofilms, and attenuation of the collagenolytic activity of pathogens that compromises intestinal healing. [21,[26][27][28]37,38] To overcome these drawbacks, we have recently developed a method for producing biocompatible nanoparticle emulsions (BCNE). [36] In producing these emulsions, we elected to exclusively utilize biocompatible, non-cytotoxic materials, with the objective of avoiding post-processing and NP separation.…”

“…Our group has used this class of NPs in various studies for the prevention of bacterial transition to virulence that could lead to sepsis, suppression of biofilms, and attenuation of the collagenolytic activity of pathogens that compromises intestinal healing. [ 21,26–28,37,38 ]…”

“…Specifically, polyethylene glycol diacrylate (PEGDA) is used in our studies. [21,[26][27][28][34][35][36][37][38] PEGDA-based gels are especially desirable because of their biocompatibility, biodegradability, U.S. Food and Drug Administration (FDA) approval for human use, inherent inert response to non-specific protein adsorption and cell adhesion, [39] and deeper penetration and circulation times in target tissues. [40] Additionally, they allow for the design and synthesis of hydrogel networks with novel molecular architecture and infrastructure, and features that could not be easily described and/or understood with traditional classical approaches.…”