Meeting the Need for Regenerative Therapies: Translation-Focused Analysis of U.S. Regenerative Medicine Opportunities in Cardiovascular and Peripheral Vascular Medicine Using Detailed Incidence Data

Abstract

Cardiac and vascular diseases represent one of the most substantial medical areas for the applications of regenerative medicine. Despite advances in endovascular repair, surgical intervention, and disease management, atherosclerosis and heart failure continue to be prominent health problems. This report analyzes the regenerative medicine treatment opportunities in both cardiovascular and peripheral vascular repair, examining the treatment opportunities for tissue-engineered vascular grafts as well as cell-based therapies. U.S. hospital discharge data were used to generate a detailed estimate of the relative target populations for cardiac and vascular disease. Gap analyses were performed for vascular access, small caliber vascular grafts, and cell-based therapies for revascularization and heart failure. The analysis compared current alternatives, gaps in medical need, and what a tissue-engineered or regenerative alternative should achieve for optimum medical and commercial feasibility. Although the number of coronary bypass grafts vastly outnumbered peripheral grafts, a detailed consideration of re-grafts and the success of first grafts combined with gap analysis (GAP) leads us to conclude that peripheral vascular disease is the more commercially feasible and attractive target opportunity for engineered small caliber grafts for the foreseeable future. Cardiac bypass would need substantial long-term clinical experience, which could be a significant hurdle. Vascular access, often regarded as a first-in-man indication, is an excellent opportunity for an engineered graft as an alternative to arteriovenous fistula that could overcome complications associated with a prosthetic graft. The GAP also suggests that for heart failure, cellular therapies should link near-term changes in repair, such as improvement in cardiac output and reduced scarring with limiting progression of the disease, reducing the need for complex pharmacologic management, and reducing rates of hospitalization. Naturally, researchers must determine where their technology and know-how can be applied most effectively, but it is clear from our analysis that an astute strategy in the use of science and technology will be important to successful translation in this space.

The Tissue-Engineered Vascular Graft—Past, Present, and Future

“…A recent study suggested that even though CABG procedures are more common, peripheral artery revascularizations and AVFs for vascular access demonstrated stronger commercial feasibility as the initial target market for the TEVG in the clinic. 279 It is also likely that in the future of healthcare, cost/benefit will not be the only justification for a new medical technology such as the TEVG. Demonstrating value to the patient and medical system is also likely to become a more important factor.…”

3D Printing Applied to Tissue Engineered Vascular Grafts

“…The surgeons anastomose the graft with a healthy vessel and reconnect the blood flow downstream. A vascular bypass is a common surgical procedure for limb salvage following critical limb ischemia and various peripheral vascular diseases associated with diabetes, atherosclerosis, or aging, and is a prevailing therapeutic option for coronary artery diseases [1]. Vascular prostheses are also essential for arteriovenous fistulae, hemodialysis vascular access, and large vessel reconstruction-linked congenital defects or aneurysms.…”

“…For applications, such as peripheral and coronary bypasses that require small diameter grafts, the benchmark vascular grafts are autologous, including the internal mammary artery, the radial artery from the arm, and the saphenous vein from the leg [1]. Although very successful in a majority of patients, the lack of natural grafts is a concern for approximately 30% of those who need multiple grafts or have vascular diseases.…”

Bioprinting in cardiovascular tissue engineering: a review

“…Damaged myocardium cannot be restored on its own as native cardiomyocytes are limited in regenerative abilities. Hence, cardiac tissue engineering aims to provide biological solutions to restore the ill-function-A ing heart and has the largest potential in regenerative medicine [7] . A potential medical solution is through injecting cells at infarct site or via intracoronary route [8][9][10][11] .…”

“…Tissue engineering is a field which applies the principles of engineering and life sciences to develop biological substitutes that can restore, maintain or improve tissue function [16] . Specifically, cardiac tissue engineering aims to provide biological solutions to restore failing hearts and has one of the largest potential in regenerative medicine [17] . With advancement of three-dimensional (3D) printing, also known as additive manufacturing, various techniques have been applied in producing patientspecific biological substitutes, ranging from orthopedic implants [18][19] to scaffolds for tissue engineering [14,20] .…”