Rheology of perfusates and fluid dynamical effects during whole organ decellularization: A perspective to individualize decellularization protocols for single organs

Abstract

The approach of whole organ decellularization is rapidly becoming more widespread within the tissue engineering community. Today it is well known that the effects of decellularization protocols may vary with the particular type of treated tissue. However, there are no methods known to individualize decellularization protocols while automatically ensuring a standard level of quality to minimize adverse effects on the resulting extracellular matrix. Here we follow this idea by introducing two novel components into the current practice. First, a non-invasive method for online monitoring of resulting fluid dynamical characteristics of the coronary system is demonstrated for application during the perfusion decellularization of whole hearts. Second, the observation of the underlying rheological characteristics of the perfusates is employed to detect ongoing progress and maturation of the decellularization process. Measured data were contrasted to the respective release of specific cellular components. We demonstrate rheological measurements to be capable of detecting cellular debris along with a discriminative capture of DNA and protein ratios. We demonstrate that this perfusate biomass is well correlated to the biomass loss in the extracellular matrix produced by decellularization. The appearance of biomass components in the perfusates could specifically reflect the appearance of fluid dynamical characteristics that we monitored during the decellularization process. As rheological measuring of perfusate samples can be done within minutes, without any time-consuming preparation steps, we predict this to be a promising novel analytic strategy to control decellularization protocols, in time, by the actual conditions of the processed organ.