Whole organ bioreactor with integrated nondestructive D molecular imaging

Abstract Significance Donor tissue shortage remains a critical problem in lung transplantation Recent advances in tissue engineering have allowed for the possibility of generating bioengineered lungs from decellularized organ scaffolds These scaffolds created from the donor s tissue become functionalized after recellularization with a patient s own cells However translation of whole lung decell recell technology to the clinic has been hampered by the lack of sophisticated tissue growth technologies e g bioreactors that are capable of providing precise feedback and control of the microenvironment within the scaffold Innovation One specific feature that all bioreactors currently lack is a way to noninvasively image the developing organs within them or quantitatively assess the seeding and growth of cells over time Currently these parameters can only be evaluated destructively by histology or by rudimentary input output assays that have no spatial sensitivity Therefore we propose a novel bioreactor that will provide a new layer of information and feedback to the user based on D contrast enhanced ultrasound photoacoustic USPA image data USPA is a new functional imaging modality that utilizes a light source to generate ultrasonic waves throughout a tissue volume This approach can provide noninvasive high resolution images of cellular distribution and cellular metabolism in D Team SonoVol Inc a company specializing in D robotic ultrasound imaging will partner with a team of tissue engineer UMN photoacoustics Johns Hopkins and medical image analysis Kitware experts to build a specialized bioreactor with integrated noninvasive molecular imaging feedback Hypothesis The USPA enabled bioreactor will improve whole organ engineering research by providing real time quantitative feedback on cellular distribution and metabolism This will accelerate the experimental feedback loop as compared to conventional histology as well as reduce costs Approach During Phase I we will demonstrate feasibility within a mouse lung During Phase II we will scale the system up for use in translational sized porcine organs and perform the commercial Randamp D necessary to deliver our first calibrated and validated systems to customers Impact This technology will be the first commercially available bioreactor of its kind specifically designed for noninvasive molecular imaging and nondestructive assessment of the D organ constructs Initially its commercial impact will be primarily focused at academic research institutions however as lung bioengineering technologies mature the technology could eventually serve a critical role in biotech after bioengineered lungs are approved for clinical use Project Narrative Tissue engineering using D scaffolds represents the future of organ transplantation Unfortunately bioengineering complex organs such as the lung or heart is currently limited by rudimentary bioreactor technologies We propose to build the world s first bioreactor system with integrated D noninvasive molecular imaging capable of evaluating organ constructs within it Not only will the product help reduce the financial burden and improve the science of basic researchers but it will also provide a method for quality controlling organ constructs once recellularized scaffolds have been successfully translated to clinical grade products