3 research outputs found
Predictive Model for Design of a 3D Developmental Neurotoxicity Platform
Exposure to developmental toxins during gestation have been shown to be linked to neurological disorders such as epilepsy, schizophrenia, and dyslexia [1] . In this report we describe efforts that represent the ground work to develop a predictive neurotoxicity model to test developmental toxicity on early neuronal differentiation from drugs and toxins for human consumption or exposure. Developmental toxins are toxins that prevent stem cell differentiation into neurons by impacting neural development [2] . Currency technologies used to evaluate a compound\u27s potential as a developmental toxin are centered around culturing stem cells in a two-dimensional environment or exposing animal models to the compound. The stem cells are then monitored for changes in proliferation, differentiation, and death. These classes of experiments proved not only to be expensive, but also extremely time consuming and ineffective in some cases. These technologies do not accurately mimic the in vivo environment, which uses ECM proteins and cell-cell interactions to regulate cellular functions such as migration, apoptosis, and gene expression. Our predictive model would provide a more biologically accurate alternative of the human system compared to two-dimensional cell culture and animal models. Our model would further improve the quality and relevance of developmental neurotoxicity research, reduce the number of animal experiments and overall cost to evaluate the potential for a compound to act as a developmental toxin
Combined Effects of Confinement and Macromolecular Crowding on Protein Stability
Confinement and crowding have been shown to affect protein fates, including folding, functional stability, and their interactions with self and other proteins. Using both theoretical and experimental studies, researchers have established the independent effects of confinement or crowding, but only a few studies have explored their effects in combination; therefore, their combined impact on protein fates is still relatively unknown. Here, we investigated the combined effects of confinement and crowding on protein stability using the pores of agarose hydrogels as a confining agent and the biopolymer, dextran, as a crowding agent. The addition of dextran further stabilized the enzymes encapsulated in agarose; moreover, the observed increases in enhancements (due to the addition of dextran) exceeded the sum of the individual enhancements due to confinement and crowding. These results suggest that even though confinement and crowding may behave differently in how they influence protein fates, these conditions may be combined to provide synergistic benefits for protein stabilization. In summary, our study demonstrated the successful use of polymer-based platforms to advance our understanding of how in vivo like environments impact protein function and structure
Multifunctional Hydrogel Nanocomposites for Biomedical Applications
Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications including tissue engineering, drug delivery, wound healing, bioprinting, and biowearable devices