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All tissue engineering and regenerative medicine scaffolds try to mimic some characteristic of the natural extracellular matrix, or ECM. It supports growth of blood vessels, nerves, and allows sufficient diffusion of nutrients to keep native tissue healthy. Usually scientists and engineers try to isolate just a few of the characteristics of the ECM, such as mechanical properties, three dimensional structure, and inclusion of proteins or other functional molecules.
A few researchers have decided to not to mimic ECM and instead use the extracellular matrix itself as a tissue engineering scaffold. The widest used example is small intestinal submucosa, or SIS, that is usually taken from pigs. Tissue is taken from an animal and decellularized so that when used as part of a therapy, it will not cause an adverse immune response. The decellularized ECM keeps its three dimensional structure, and the growth factors can survive the processing. Decellularized ECM scaffolds placed into a wound site initiates natural remodeling processes and have proven to be biocompatible and effective in many applications.
In the last few years, researchers have moved beyond decellularization of tissue to decellularization of whole organs. The thicker tissue of an intact organ presents new challenges for decellularization protocols because it is now more difficult to get all of the cellular components out of the tissue. Many different protocols exist that use detergents and solvents to help the process.
Giuseppe Orlando and his team have developed a protocol that successfully decellularizes whole human kidneys. They observed that a large number of kidneys from organ donors are discarded because they don’t meet the strict guidelines of a viable candidate for transplant. Dr. Orlando and his team have suggested that these human organs could be used as decellularized organ scaffolds that could then be recellularized, possibly by the patient’s own cells.
In this episode of the Natural Scaffolds Review, we have an interview with Dr. Orlando where he discusses the portion of his work related to this work with decellularized human kidneys and how they might be used in the future. I also discuss other recent publications describing whole organ decellularization. Links to the articles discussed in the episode are included below.
Giuseppe Orlando, et al. “Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.” Biomaterials 34(24):5915-5925, 2013.
Additional publications mentioned in podcast:
Paula N. Nonaka, et al. “Effects of freezing/thawing on the mechanical properties of decellularized lungs.” Journal of Biomedical Materials Research A 102A(2):413-419, 2014.
Simon Farnebo, et al. “Reconstruction of the tendon-bone insertion with decellularized tendon-bone composite grafts: Comparison with conventional repair.” Journal of Hand Surgery 39(1):65-74, 2014.
Simon Farnebo, et al. “Decellularized tendon-bone composite grafts for extremity reconstruction: An experimental study.” Plastic and Reconstructive Surgery 133(1):79-89, 2014.
Silvia Baiguerra, et al. “Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering.” Biomaterials 35(4):1205-1214, 2014.
Alessandro Gonfiotti, et al. “The first tissue-engineered airway transplantation: 5-year follow-up results.” Lancet 383:238-244, 2014.