RESUMO
Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model substances on the human nail plate and a model membrane from the horse hoof was investigated. A linear correlation was found between drug uptake by the human nail plate and the uptake by the equine hoof. The developed and established permeation device is suitable for investigations of ungual drug transport and enables the use of different membrane diameters and the use of a gel-based nail bed analog. The hydrogel-based acceptor medium used ensures adequate stabilization and hydration of the nail membrane.
RESUMO
Bioprinting for tissue or disease models is a promising but complex process involving biofabrication, cell culture and a carrier material known as bioink. The native extracellular matrix (ECM), which forms the scaffold for cellsin vivo, consists of several components including collagen as a gelling agent to confer mechanical stiffness and provide a substrate for cell attachment. Bioprinting therefore needs an artificial ECM that fulfills the same functions as its natural counterpart during and after the printing process. The combination of bioink materials determines the immune response of the host, cell compatibility and adhesion. Here we evaluate multi-material blending with four pre-selected components using a design of experiments approach. Our exemplary designed hydrogel is highly reproducible for the development of artificial ECM and can be expanded to incorporate additional requirements. The bioink displays shear-thinning behavior and a high zero-shear viscosity, which is essential for the printing process. We assessed the printing behavior of our bioink over a wide range of the key process parameters for extrusion-based bioprinting (temperature, pressure, feed rate, and nozzle geometry). Several processing temperatures were linked by rheological measurements directly to the 3D printing process. The printing results were evaluated using a self-developed categoric strand screening process, varying the feed rate and pressure with a fixed nozzle. Accordingly, nozzles differing in size and shape were evaluated and the interactions between printing pressure and feed rate were characterized separately by applying a modified O-R-O test. We tested the short-term cultivation stability of our bioink to mimic the hypothermic and hyperthermic conditions of the human body. As result we present an expandable concept for bioink development and a highly reproducible and well-characterized procedure for printing with the newly developed hydrogel. We provide detailed insights into the relationship between printing parameters, rheological parameters and short-term cultivation stability.
