Delivery of Antioxidant and Anti-inflammatory Agents for Tissue Engineered Vascular Grafts

Abstract

The treatment of patients with severe coronary and peripheral artery disease represents a significant clinical need, especially for those patients that require a bypass graft and do not have viable veins for autologous grafting. Tissue engineering is being investigated to generate an alternative graft. While tissue engineering requires surgical intervention, the release of pharmacological agents is also an important part of many tissue engineering strategies. Delivery of these agents offers the potential to overcome the major concerns for graft patency and viability. These concerns are related to an extended inflammatory response and its impact on vascular cells such as endothelial cells. This review discusses the drugs that have been released from vascular tissue engineering scaffolds and some of the non-traditional ways that the drugs are presented to the cells. The impact of antioxidant compounds and gasotransmitters, such as nitric oxide and carbon monoxide, are discussed in detail. The application of tissue engineering and drug delivery principles to biodegradable stents is also briefly discussed. Overall, there are scaffold-based drug delivery techniques that have shown promise for vascular tissue engineering, but much of this work is in the early stages and there are still opportunities to incorporate additional drugs to modulate the inflammatory process.

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

“…For none of these materials do we have an answer to two of the critical questions asked at the beginning: (1) as scaffolds, do they allow transmural endothelialisation or alternatively facilitate true fall-out endothelialisation and (2) given the absence of trans-anastomotic neointimal outgrowth in man: is scaffold degradation (eg., by blood borne inflammatory cells) balanced against neo-tissue formation to prevent a premature structure-loss in patients? The same questions need to be asked with regards to the effect of incorporated/grafted bioactive molecules such as VEGF (361,366,367,409), NO (364), TGF-b (410), SFD-1 (411), and many others (368,412) not to mention the various ingrowth gels whether they are from natural proteins (388,407,413,414) or fully synthetic (415); functionalised, (416)(417)(418)(419)(420)(421)(422) and/or potentially cell selective (423). For gels, however, an important second purpose may emerge as "space-holders" further facilitating transmural endothelialisation.…”

Targeted Delivery of Bioactive Molecules for Vascular Intervention and Tissue Engineering

“…Delayed release of anti-inflammatory molecules days or weeks after TEBV implantation is another potential application of controlled release. While the inflammatory response may be critical immediately following implantation, delayed release of anti-inflammatory molecules may prevent problems such as intimal hyperplasia from occurring later ( Washington and Bashur, 2017 ).…”

Soluble cyanobacterial carotenoprotein as a robust antioxidant nanocarrier and delivery module

“…Carotenoids are excellent natural antioxidants but their delivery to vulnerable cells is challenging due to their hydrophobic nature and susceptibility to degradation. Thus, systems securing antioxidant stability and facilitating targeted delivery are of great interest for the design of medical agents (13,15,(33)(34)(35)(36)(37). In this work, we have demonstrated that CTDH can deliver ECN into membranes of liposomes and mammalian cells with almost 70 % efficiency, which, in Tet21N cells, alleviates the induced oxidative stress.…”