Carbon monoxide (CO) is a gasotransmitter that plays important roles in regulating cell functions and has shown therapeutic effects in clinic studies. CO releasing molecules (CORMs), which allow controlled release of CO in physiological conditions, have been intensively studied in the past decade. While most CORMs are metal complexes, several nonmetallic CORMs have also been developed and most of them were reported in recent years. The major advantages of nonmetallic CORMs are potentially low toxicity and easy modification for property tuning. Syntheses, CO-release mechanisms, biological behaviors, and physicochemical properties of these nonmetallic CORMs are reviewed here. The first part of this short review covers the nonmetallic CORMs that do not require irradiation to release CO, which includes methylene chloride, CORM-A1 and its derivatives, amine carboxyboranes, and bimolecular CORMs. The second part focuses on the CORMs that release CO under irradiation (PhotoCORMs) including unsaturated cyclic diketones, xanthene carboxylic acids, meso-carboxy BODIPYs, and hydroxyflavones. Future prospects are discussed at the end of this review.
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.
A new organic photoCORM encapsulated in a poly(butyl cyanoacrylate) nanoparticle showed nearly quantitative CO release under visible light and low cytotoxicity.
A clinically approved, tissue engineered graft is needed as an alternative for small‐diameter artery replacement. Collagen type I is commonly investigated for naturally derived grafts. However, collagen promotes thrombosis, currently requiring a graft pre‐seeding step. This study investigates unique impacts of blending low collagen amounts with synthetic polymers on scaffold platelet response, which would allow for viable acellular grafts that can endothelialize in vivo. While platelet adhesion and activation are confirmed to be high with 50% collagen samples, low collagen ratios surprisingly exhibit the opposite, anti‐thrombogenic effect. Different platelet interactions in these blended materials can be related to collagen structure. Low collagen ratios show homogenous distribution of the components within individual fibers. Importantly, blended collagen scaffolds exhibit significant differences from gelatin scaffolds, including retaining percentage of collagen after incubation. These findings correlate with functional benefits including better endothelial cell spreading on collagen versus gelatin blended materials. This appears to differ from the current paradigm that processing with harsh solvents will irreversibly denature collagen into less desirable gelatin, but an important distinction is the interaction between collagen and synthetic materials during processing. Overall, excellent anti‐thrombogenic properties of low collagen blends and benefits after grafting show promise for this vascular graft strategy.
Regenerative engineering is defined as the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems. It is an expansion of tissue engineering, which was first developed as a method of repair and restoration of human tissue. In the past three decades, advances in regenerative engineering have made it possible to treat a variety of clinical challenges by utilizing cutting-edge technology currently available to harness the body’s healing and regenerative abilities. The emergence of new information in developmental biology, stem cell science, advanced material science and nanotechnology have provided promising concepts and approaches to regenerate complex tissues and structures.
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