Broadly, the Miromatrix technology encompasses a method to decellularize and recellularize whole or partial organs and tissues. The technology is based on a proprietary method for removing all cells while maintaining a non-cellular (called extracellular) matrix or scaffold with its original architecture, mechanical properties, and a vascular network capable of maintaining physiological pressures. In the regenerative medicine field, biologic efforts using porcine, bovine, and human donor material have achieved only limited success because they are constrained by the available technology. The most widely recognized method of removing cells in use today is “immersion decellularization” in which an organ is soaked in a vat of harsh detergent which migrates from the outer surface inward, and then back out once the cells are dissolved. This method damages the organ capsule through mechanical or enzymatic methods, and the cells within the organ begin to break down before being exposed to the detergent, releasing various enzymes that also degrade the surrounding scaffold. The end result is a partially degraded scaffold with a compromised vascular network and an outer organ capsule that will not maintain physiological pressures when tested. In addition, cells no longer recognize this degraded scaffold as the appropriate environment in which to become functional. Since the immersion decellularization process is passive it also takes a longer time than our technology to process tissues. These issues are further complicated as applied to bone due to the current demineralization techniques.
Miromatrix’ perfusion decellularization technology is in contrast to immersion decellularization and overcomes the hurdles of immersion by facilitating rapid access to the whole organ through the native vasculature by cannulating the vasculature and perfusing (running) a mild detergent solution through the native blood vessels as opposed to immersing the organ. Because organs are dense with vascular capillaries, most cells are located in close proximity to a capillary, resulting in an exponential increase in the effective surface area of the detergent and decreased time to dissolve the cellular material as it is expelled through the venous system (as opposed to through the organ wall or capsule). In short, this two or more day process (depending on what is being decellularized) utilizes the organ’s natural plumbing to rapidly remove the cells from the inside-out in approximately one-third of the time it takes utilizing immersion. More importantly, the end result is a completely preserved native scaffold containing the appropriate microenvironment required for the introduction of organ-specific cells, along with an intact vascular network to reconnect to the patient’s blood supply and outer capsule capable of maintaining physiological pressures. These components are critical for the later use of the Miromatrix recellularization technology, which also uses perfusion to repopulate vascular and organ-specific regenerative cells onto the organ, where they migrate to the appropriate microenvironment (since the “signals” that tell a cell what to do remain intact on the Miromatrix scaffold), as the organs are grown and matured in bioreactors under normal physiological conditions. The resulting organs can be transplanted utilizing the same techniques as current organ transplantation.
Decellularization of a Porcine Heart
Scaffolds created with the Miromatrix technology are capable of receiving and incorporating a variety of cell types, depending on the organ scaffold utilized. Moreover, as cell type discovery continues to grow, the fact that scaffolds created with this technology are of a natural biological design make them an ideal template to support the growth and differentiation of stem cells into functional tissues, organs and bioidentical test beds.