Individualized Decellularization for Tissue Engineering Tissues and Organs in Animals and Humans

Tissue engineering is an emerging field which offers promising therapeutic options for many patients with incurable diseases. One method of producing a scaffold for TE is decellularization, which aims to remove immunogenic elements from a donor organ without compromising its inherent structural and biomechanical properties. Presently, optimizing a suitable decellularization protocol for a particular organ is a time-consuming, trial-and-error based task. The resulting protocol is then used for all organs of the same type, without considerations of donor differences. To this end, we have developed a system based on mathematical modeling, which tailors the decellularization to each individual organ. The system uses real-time image analyses to predict complete decellularization while also changing reagents automatically in order to eliminate operator-variability. We verified the system using organs from rat esophagus and small intestine. The produced biological scaffolds’ architecture was evaluated by histology and electron microscopy, retained ECM-protein composition by immunohistochemistry and residual DNA content by nucleic acid staining and quantification. Biomechanical evaluations of native and decellularized tissue were performed to study the impact on mechanical strength. Prematurely stopping the decellularization resulted in inadequate removal of cell nuclei. We further validated the prediction model using human esophageal samples. In conclusion, by tailoring the decellularization to each individual organ our novel method improve the quality of produced scaffolds. The method is likely to be of greatest importance for human samples, where donor differences are considerable.