Pentagalloyl glucose-stabilized decellularized bovine jugular vein valved conduits as pulmonary conduit replacement.

Congenital heart diseases (CHD) are one of the most frequently diagnosed congenital disorders, affecting approximately 40,000 live births annually in the United States. Out of the new patients diagnosed with CHD yearly, an estimated 2,500 patients require a substitute, non-native conduit artery to replace structures congenitally absent or hypoplastic. Devices used for conduit replacement encounter limitations exhibiting varying degrees of stiffness, calcification, susceptibility to infection, thrombosis, and a lack of implant growth capacity. Here, we report the functionality of pentagalloyl glucose (PGG) stabilized decellularized valved bovine jugular vein conduit (PGG-DBJVC). The PGG-DBJVC tissues demonstrated mechanical properties comparable to native and glutaraldehyde fixed tissues, while exhibiting resistance to both collagenase and elastase enzymatic degradation. Subcutaneous implantation of tissues established their biocompatibility and resistance to calcification, while implantation in sheep in the pulmonary position demonstrated adequate implant functionality, and repopulation of host cells, without excessive inflammation. In conclusion, this PGG-DBJVC device could be a favorable replacement option for pediatric patients, reducing the need for reoperations required with current devices. STATEMENT OF SIGNIFICANCE: Congenital Heart Disease (CHD) is a common congenital disorder affecting many newborns in the United States each year. The use of substitute conduit arteries is necessary for some patients with CHD who have missing or underdeveloped structures. Current conduit replacement devices have limitations, including stiffness, susceptibility to infection and thrombosis, and lack of implant growth capacity. Pentagalloyl glucose-stabilized bovine jugular vein valved tissue (PGG-DBJVC) offers a promising solution as it is resistant to calcification, and biocompatible. When implanted in rats and as pulmonary conduit replacement in sheep, the PGG-DBJVC demonstrated cellular infiltration without excessive inflammation, which could lead to remodeling and integration with host tissue and eliminate the need for replacement as the child grows.

Role of elastic fiber degradation in disease pathogenesis.

Elastin is a crucial extracellular matrix protein that provides structural integrity to tissues. Crosslinked elastin and associated microfibrils, named elastic fiber, contribute to biomechanics by providing the elasticity required for proper function. During aging and disease, elastic fiber can be progressively degraded and since there is little elastin synthesis in adults, degraded elastic fiber is not regenerated. There is substantial evidence linking loss or damage of elastic fibers to the clinical manifestation and pathogenesis of a variety of diseases. Disruption of elastic fiber networks by hereditary mutations, aging, or pathogenic stimuli results in systemic ailments associated with the production of elastin degradation products, inflammatory responses, and abnormal physiology. Due to its longevity, unique mechanical properties, and widespread distribution in the body, elastic fiber plays a central role in homeostasis of various physiological systems. While pathogenesis related to elastic fiber degradation has been more thoroughly studied in elastic fiber rich tissues such as the vasculature and the lungs, even tissues containing relatively small quantities of elastic fibers such as the eyes or joints may be severely impacted by elastin degradation. Elastic fiber degradation is a common observation in certain hereditary, age, and specific risk factor exposure induced diseases representing a converging point of pathological clinical phenotypes which may also help explain the appearance of co-morbidities. In this review, we will first cover the role of elastic fiber degradation in the manifestation of hereditary diseases then individually explore the structural role and degradation effects of elastic fibers in various tissues and organ systems. Overall, stabilizing elastic fiber structures and repairing lost elastin may be effective strategies to reverse the effects of these diseases.