Multifunctional nanoscale strategies for enhancing and monitoring blood vessel regeneration

Abstract

Nanomedicine has great potential in biomedical applications, and specifically in regenerative medicine and vascular tissue engineering. Designing nanometer-sized therapeutic and diagnostic devices for tissue engineering applications is critical because cells experience and respond to stimuli on this spatial scale. For example, nanoscaffolds, including nanoscalestructured or nanoscale surface-modified vascular scaffolds, can influence cell alignment, adhesion, and differentiation to promote better endothelization. Furthermore, nanoscale contrast agents can be extended to the field of biomedical imaging to monitor and track stem cells to better understand the process of neovascularization. In addition, nanoscale systems capable of delivering biomolecules (e.g. peptides and angiogenic genes/proteins) can influence cell behavior, function, and phenotype to promote blood vessel regeneration. This review will focus on nanomedicine and nanoscale strategies applied to vascular tissue engineering. In particular, some of the latest research and potential applications pertaining to nanoscaffolds, biomedical imaging and cell tracking using nanoscale contrast agents, and nanodelivery systems of bioactive molecules applied to blood vessel regeneration will be discussed. In addition, the overlap between these three areas and their synergistic effects will be examined as related to vascular tissue engineering.

Heparinized PLLA/PLCL nanofibrous scaffold for potential engineering of small‐diameter blood vessel: Tunable elasticity and anticoagulation property

“…Biomimetic nanofibrous structure is a key characterization for ideal vascular tissue engineering scaffold, because it could provide biomimetic microenvironment for cells and facilitate their adhesion, proliferation, and differentiation. [11][12][13][14] TIPS is a facile way to prepare nanofibers, 19,20 which is considered as a promising method for fabricating 3D nanofibrous scaffolds. PLLA is a frequently used polymer to be fabricated into nanofibrous scaffold by TIPS.…”

“…1,3,4 Synthetic vascular prostheses such as expanded polytetrafluoroethylene and polyethylene terephthalate have been successfully used in clinical applications as large diameter (inner diameter 6 mm) vessel replacement, but failed when used for small diameter (inner diameter <6 mm) vascular applications due to thrombosis and intimal hyperplasia. [11][12][13][14] So far, several methods have been developed to fabricate nanofibrous scaffolds for simulating the structure and function of the native ECM, such as electrospinning, [15][16][17][18] thermally induced phase separation (TIPS), 19,20 and molecular self-assembly. [7][8][9][10] To increase the success of engineered vascular grafts, the blood vessel constructs are commomly designed to mimic the structure, biologic, and mechanical properties of native blood vessels.…”

“…The extracelluar matrix (ECM) within native blood vessel consists predominantly of nanoscaled fibrous proteins such as collagen and elastin, which are assembled into a three-dimensional (3D) fibrillar network that contributes to vessel mechanical properties and critically regulates cell behavior. [11][12][13][14] So far, several methods have been developed to fabricate nanofibrous scaffolds for simulating the structure and function of the native ECM, such as electrospinning, [15][16][17][18] thermally induced phase separation (TIPS), 19,20 and molecular self-assembly. [21][22][23] Among these approaches, TIPS is a facile method to fabricate nanofibers in the same size range as natural ECM collagen fibers (50-500 nm).…”

Nanoscale Strategies: Treatment for Peripheral Vascular Disease and Critical Limb Ischemia

“…In the future, multiplexed NPs carrying multiple enzymes and growth factors with optimum stoichiometry and sequential release may be developed to further enhance the angiogenic effects. 44 …”

Translational Imaging for Regenerative Medicine

“…Blood vessel regeneration involves selecting a biomaterial-for example, solid materials such as nanoscale electrospun fibers, cell-encapsulated nanogels, or chemically or physically modified vascular grafts-and selecting a suitable cell type (e.g., stem cells, progenitor cells, and differentiated cells) [65]. Magnetic resonance angiography is routinely used to image blood vessel networks.…”