UC Davis researchers announced on June 12 that they have received a $4 million grant from the National Institutes of Health to develop and test a bioengineered graft with ligands designed to improve bladder reconstruction for children with neuropathic bladders caused by spina bifida or spinal cord injuries.
Eric Kurzrock, chief of pediatric urologic surgery and professor at UC Davis Children's Hospital, said his team will use the funding to further research on vascularized grafts that could address complications associated with standard enterocystoplasty. "The bladder is so unique because it is free floating with no supporting matrix of cells around it. It has been historically challenging for regeneration and augmentation," Kurzrock said. He added, "Patients with spina bifida or spinal cord injury may develop a neurogenic bladder, leading to problems with urination and kidney function. They may need bladder augmentation to enlarge their bladder."
The research brings together clinical and bioengineering expertise in an effort to create graft tissues containing functioning blood vessels, which are essential for survival after transplantation. Traditional enterocystoplasty uses parts of the intestine or stomach as graft material but requires major abdominal surgery and can result in various complications.
Kurzrock previously published a study showing that vascularized grafts implanted in mice and pigs developed connections between host and graft blood vessels within days, facilitating blood flow throughout the tissue. He collaborates with Aijun Wang, professor of surgery and biomedical engineering at UC Davis, who has developed a scaffold made from engineered biomaterial modified by LXW7 ligand molecules that interact specifically with endothelial cells involved in vascularization.
Wang explained, "When these molecules are added to scaffolds, they provide a gripping site for endothelial cells to bind. This allows for better interaction between the cells and their supportive structure, known as extracellular matrix." The engineered pig tissue used as the scaffold is processed to remove its original cells while retaining its protein structure; this approach aims to prevent immune rejection when implanted.
The modified grafts are first implanted onto muscle tissue before being transplanted into the bladder area so they mature optimally before final placement. Wang said, "It's a brilliant idea to integrate the body's own healing potential... Adding newer bioengineering technologies, such as the ligand technology, will help in microvascular regeneration of the whole bladder matrix and nearby muscle cells." The team plans further testing in pig models prior to human clinical trials.
