Atherosclerosis is a highly prevalent disease that can significantly increase the risk of major vascular events, such as myocardial or cerebral infarctions. The anoxemia theory states that a disparity between oxygen supply and demand contributes to atherosclerosis. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric protein, part of the basic helix-loop-helix family and one of the main regulators of cellular responses in a low‑oxygen environment. It plays a key role in the development of atherosclerosis through cell-specific responses, acting on endothelial cells, vascular smooth muscle cells (SMCs) and macrophages. Through the upregulation of VEGF, NO, ROS and PDGF, HIF-1 is able to cause endothelial cell dysfunction, proliferation, angiogenesis and inflammation. Activation of the NF-kB pathway in endothelial cells is an important contributor to inflammation and positively feedbacks to HIF-1. HIF-1 also plays a significant role in both the proliferation and migration of smooth muscle cells - two important features of atherosclerosis, while the formation of foam cells (lipid-laden macrophages) is also a critical step in atherosclerosis and mediated by HIF-1 through various mechanisms such as dysfunctional efflux pathways in macrophages. Overall, HIF-1 exerts its effect on the pathogenesis of atherosclerosis via a variety of molecular and cellular events in the process. In this review article, we examine the effects HIF-1 on vascular cells and macrophages in the development of atherosclerosis, highlighting the environmental cues and signalling pathways that control HIF-1 expression/activation within the vasculature. We will highlight the potential of HIF-1 as a therapeutic target on the disease development.

3D printing has enabled the design of biomaterials into intricate and customized scaffolds. However, current 3D printed biomaterial scaffolds have potential drawbacks due to residual monomers, free-radical initiators, solvents, or printing at elevated temperatures. This work describes a solvent, initiator, and monomer-free degradable polyester platform for room temperature 3D printing. Linoleic acid side chains derived from soybean oil lowers the T g and prevents packing and entanglement, ensuring that G″ > G′ during room temperature printing. Upon printing, cross-linking of pendant functionalized coumarin moieties fixes the viscous filaments to elastomeric solids. Furthermore, the modular design of the polyester platform enables conjugation of ligands, as demonstrated by the conjugation of FITC to surface amines on the 3D printed scaffolds. This low modulus, printable polyester platform addresses several design challenges in 3D printing of functional biomaterials and could potentially be useful in many tissue engineering applications.

In spite of the rapid adoption of three-dimensional (3D) printed scaffolds in biomedical applications, there is a paucity of low-modulus 3D printable biodegradable polymers available for fabrication of tissue-mimetic scaffolds. Extrusion-based direct-write 3D printing (EDP) enables printing and customization of lowmodulus materials that match the modulus of the native tissue. However, the poor printability and low shape fidelity of such materials are significant limitations of soft materials. Herein, we demonstrate that these limitations can be overcome by the introduction of hydrogen bonds into 3D printable low-modulus polyester inks. We show that the hydrogen bonds serve as physical cross-links, which improve the printability and shape fidelity of 3D printed scaffolds without sacrificing the low modulus of the polyester. A 3D printable polyester ink comprising an unsaturated aliphatic side chain, a UV-curable coumarin pendant group, and a secondary amide group-containing side chain was designed. The long aliphatic side chains increase the flowability and allow 3D printing at room temperature. Coumarin groups function as crosslinking sites when irradiated with UV light, which help the scaffold maintain its shape after printing. The hydrogen bonds from the secondary amide groups impede the deformation of filament dimensions after extrusion and result in higher shape fidelity. Most significantly, introduction of hydrogen bonds does not compromise the softness of the polymer, which facilitates room-temperature printing and maintains the low-modulus nature of the polymer post printing.

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