Development of an advanced research bioreactor for regenerating lung tissue, including complete human size lungs, is proposed. This reactor will be capable of decellularizing a human-size lung and using the resulting scaffold to bioengineer an autologous lung through recellularization. This requires efficient means to deposit cells and biologics on the airway walls while maintaining the gas-liquid interface and the breathing action. Also, it is desirable to operate the reactor in a closed chamber and automate the process, while closely monitoring the critical process parameters. Our proposed approach is to adapt a proprietary spraying catheter technology to the lung bioreactor and leverage the applicantÂ’s expertise in automation and control to develop the advanced bioreactor system. The proposed airway sprayer will be capable of accessing the trachea and bronchi of the lung scaffold and safely deposit liquids containing cells and biologics on the airway walls. Airway sprayer will generate liquid aerosols that will be transported deep in the lungs with the aid of a ventilator, which will maintain the breathing action during and after the agent delivery. The base technology is already proven to gently aerosolize cells and large molecules. In this Phase I SBIR project, we propose to further develop airway sprayer technology and validate it in an existing bioreactor. We propose to optimize the device for the best cell delivery outcomes and incorporate an angulation mechanism to access the bronchi. Further, we plan to include an aspiration channel in the catheter device to sample cell secretions for efficient monitoring and control of the recellularization process. Successful completion of this work would establish the feasibility of the novel airway recellularization technique. In Phase II, this device will be incorporated in a fully automated lung research bioreactor. This advanced bioreactor system will be commercialized and made available to the research community.
Public Health Relevance Statement: PROJECT NARRATIVE The proposed lung research bioreactor will provide the researchers a powerful tool to experiment with the means to bioengineer autologous lungs and lung tissue, which would be well tolerated by the recipient and would be available as needed. The proposed research would help improve the outcome of lung transplant and lung reconstruction surgeries. Hence, this project is very relevant to public health.
Project Terms: Advanced Development; aerosolized; Aerosols; Air; Airway Resistance; Aspirate substance; Autologous; Automation; base; Biological Factors; Biomedical Engineering; Bioreactors; Blood Vessels; Breathing; Bronchi; Catheters; Cell Differentiation process; cell growth; Cell physiology; Cell secretion; Cells; commercialization; Communities; Deposition; Development; Devices; Diffusion; Distal; Drug Delivery Systems; endotracheal; Environmental air flow; Epithelial Cells; Evaluation; experimental study; Family suidae; Film; Gases; Growth; Growth Factor; Health; Histologic; Human; Humidity; improved outcome; Light; Liquid substance; Lung; lung lobe; Lung Transplantation; Measures; Mechanics; Monitor; Natural regeneration; novel; Nutrient; operation; optical fiber; Outcome; Patients; Perfusion; Phase; Physiological; Positioning Attribute; pre-clinical trial; pressure; Price; Process; process repeatability; Property; Protocols documentation; Public Health; Pulmonary function tests; Reconstructive Surgical Procedures; Research; Research Personnel; Sampling; scaffold; Small Business Innovation Research Grant; stem; Stem cells; Sterility; Structure of parenchyma of lung; System; Techniques; Technology; Testing; Time; tool; Trachea; Tube; Vascular resistance; Ventilator; Water; Work
