Biologically Engineered Growing Heart Conduits
Abstract
Normally, the blood pathway from the right ventricle of the heart to the lungs for oxygenation is comprised of a main pulmonary artery that splits into the right and left pulmonary arteries (PA branches), which supply blood to the right and left lungs, respectively. There are several related malformations of the heart that result in missing or closed PA branches. These require surgical repair and implantation of one or more tubes to reconstruct the branches. The current standard of care is to use cadaver vessel (if available) or synthetic tubes (e.g., Gortex); however, these grafts do not grow, and inevitable development of outflow resistance as the patient grows but the graft does not, resulting in right heart overload that necessitates one or more surgical reoperations to up-size the conduit. There are 50-100 such cases per year in the U.S. annually. We have developed a novel biologically engineered tube of collagenous matrix produced from a donor skin cell. The donor cells are removed with detergents so that the material can be stored and should not cause an immune response when implanted into a patient. It is thus an off-the-shelf medical product. We have shown it becomes a populated by the recipient’s cells and grows in size like the adjacent native artery when implanted into the pulmonary artery of a lamb as it grows into adult sheep size over nearly 12 months, the first-ever report of normal growth of an acellular material. Use of our biologically engineered tube could reduce multiple open heart surgeries for repair of PA branch malformation to just one open heart surgery (and eventually be used to repair many other congenital heart defects that afflict 1% of newborns in the U.S. per the National Organization for Rare Disorders NORD, or 38,500 cases each year). With a PRMRP Technology/Therapeutic Development Award grant, we will produce tubes under strict manufacturing and testing conditions that adhere to the requirements of the U.S. Food and Drug Administration (FDA) and other standards for clinical use. They will be stored for use in a phase 1 clinical trial that establishes the safety and efficacy of these tubes of cell-produced collagenous matrix for PA branch reconstruction. An Investigational New Drug (IND) submission will be made for this clinical trial as well with this grant along with additional preclinical testing that the FDA may require for approval of the IND. Additionally, we will construct valved conduits from these tubes that have also been shown to in lambs over 12 months implantation, have them independently tested to prevailing standards, and submit a preIND to the FDA. Valved conduits that can grow can be used to repair the defective pulmonary outflow tract common to the 1,300 cases of Tetralogy of Fallot in the U.S. each year per NORD, again obviating the need for multiple up-sizing reoperations required in current practice because no valves in clinical use have growth capacity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210489
Entities
People
- Robert Tranquillo
Organizations
- United States Army
- University of Minnesota