Tissue Engineering a Novel Alveolar-Capillary Interface Within Microchannels

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DESCRIPTION (provided by applicant): Pulmonary hypoplasia is a condition of the newborn characterized by the incomplete development of lung tissue whose mortality is reported as high as 54-89% Pathologic evaluation of diseased lungs reveals incomplete development of the bronchial and arterial structures as well as immaturity and a reduction of the numbers of alveoli. Tissue engineering is one method which may allow for supplementation of an underdeveloped lung. A number of successful efforts have been able to demonstrate three dimensional pulmonary constructs in hydrogels utilizing mixed populations of fetal pulmonary cells which produced structures similar to the terminal respiratory unit of the alveolus. However, a major obstacle in building a three dimensional lung construct that will be clinically useful is vascularization of any engineered pulmonary tissue as well as providing an interface through which gas can travel directly to the alveoli and be exchanged. Microelectromechanical systems (MEMS) is a powerful technology developed within the semiconductor and microelectronics industries which can control features at length scales from <1 |jm to >1 cm. The emergence of soft lithography techniques have allowed for the development of microscale devices in biocompatible polymers such as poly(dimethyl siloxane) (PDMS). Previous work within closed channels on PDMS microchips have shown the ability to construct artificial capillary networks confluent with endothelial cells and other studies have shown that PDMS channels can be utilized as conduits for gas. Thus, the specific hypothesis behind this proposed research is that a successful three dimensional model of the aveolar-capillary interface can be developed within a dual layer PDMS microchannel device populated with a mixed population of murine fetal pulmonary cells. One layer of the planned microdevice will be designed to provide a continuous nutrient supply while the second layer will be utilized to expose the alveolar-capillary interface to gas. These investigations seek to lay the foundation for the development of a novel alveolar-capillary interface within microchannels which may serve as the first step towards a more- clinically useful pulmonary tissue construct. Additionally, lessons learned from the application of microfabrication technology to tissue vascularization within this proposal may be useful for organ building efforts beyond the lung.