Building a Lifeline: Utilizing the body as a bioreactor to develop a living vascular access graft for patients with chronic kidney disease

Abstract

Patients with cardiovascular disease (CVD) or chronic kidney disease (CKD) often require vascular grafts, but autologous veins, which are preferred for their durability and lower infection risk, are not always available. Synthetic grafts, though a common alternative, tend to have poorer long-term outcomes and higher risks of complications, such as vessel wall thickening, calcification, and clotting. In situ tissue engineering (TE) offers a promising solution by using biodegradable synthetic grafts that gradually transform into autologous blood vessels through the body’s natural regenerative processes. This dissertation explores the potential of in situ TE to create functional, self-healing vascular grafts that adapt to the body over time. It demonstrates that supramolecular polymers can integrate effectively with the body's tissue without compromising cell function. In rat models, CKD did not significantly affect graft degradation or tissue formation, although increased vascular calcification was observed. Bio-functionalizing the materials to attract immune cells and support regeneration had no significant impact. The use of a faster-degrading polymer to promote neo-tissue formation led to critical graft failures, as lab-predicted degradation rates did not match real-life outcomes, underscoring the importance of cautious translation from lab studies to in vivo applications. In a large-animal model using goats, the synthetic grafts were almost completely resorbed and replaced by living vascular tissue within three months. However, this did not result in better performance compared to standard synthetic grafts. Despite this, the study demonstrates that an in situ tissue engineering (TE) approach, using the body as a bioreactor, holds great potential for developing tissue-engineered blood vessels. It also showed that repeated punctures were possible, with a clear healing and remodeling response, without causing permanent damage or negatively impacting tissue formation. Although vascular TE blood vessels are promising for vascular replacement or access, challenges such as stenosis—similar to those seen in current clinical practice—were encountered. Future innovations in vascular TE should focus on understanding the underlying remodeling processes to minimize the need for frequent interventions. Nevertheless, this approach highlights the potential of combining the body’s natural regenerative capacity with synthetic, cell-free, biodegradable electrospun materials. These vessels are immediately functional and, when degradation and tissue formation are balanced, can rapidly transform into autologous, living blood vessels capable of withstanding repeated punctures.