Congenital malformations, such as esophageal atresia, gastroschisis, congenital diaphragmatic hernia, and cutis aplasia remain a leading cause of neonatal morbidity and mortality. Traditional surgical reconstructive approaches have included the use of prosthetic materials, transfer of adjacent healthy tissues, and transplantation from donor individuals. These options are particularly limited in neonates, however, secondary to rapid growth, limited availability of healthy tissue for reconstruction, and lack of age and size-matched donor individuals. Tissue engineering is a multidisciplinary field that combines engineering and the life sciences to create structures, which restore, replace or augment tissues that have been lost secondary to congenital deficiency, disease, or trauma. The most common methodology combines bioresorbable polymer scaffolds and autologous cells that have been expanded in tissue culture to form new tissues. This approach holds particular promise for generating surgical replacement structures for reconstruction of several congenital malformations. There have been significant advances in engineering avascular tissues, such as cartilage. There has also been some success in generating, """"""""thin"""""""" tissues, such as cardiac leaflets and cultured skin substitutes. When tissues less than 2mm in thickness are transplanted, their metabolic requirements are supported initially through diffusion and later by the ingrowth of new blood vessels from adjacent structures. Thicker tissues, however, cannot rely initially on diffusion and are unable to survive the period required for vascular ingrowth. Thus, one strategy to engineer thicker tissues is to incorporate a blood supply de novo - assembling a microvasculature in tissue culture prior to implantation, allowing other cell types to grow around it, and then connecting this with existing vessels using microsurgical techniques. The principal objective of this project is to create a three-dimensional, branching, functional microvascular network in vitro which will provide a structural and metabolic framework to permit the engineering of thicker vascularized tissues for surgical reconstruction.
