Tissue engineering of small diameter (<5 mm) blood vessels is a promising approach for developing viable alternatives to autologous vascular grafts. It involves in vitro seeding of cells onto a scaffold on which the cells attach, proliferate, and differentiate while secreting the components of extracellular matrix that are required for creating the tissue. The scaffold should provide the initial requisite mechanical strength to withstand in vivo hemodynamic forces until vascular smooth muscle cells and fibroblasts reinforce the extracellular matrix of the vessel wall. Hence, the choice of scaffold is crucial for providing guidance cues to the cells to behave in the required manner to produce tissues and organs of the desired shape and size. Several types of scaffolds have been used for the reconstruction of blood vessels. They can be broadly classified as biological scaffolds, decellularized matrices, and polymeric biodegradable scaffolds. This review focuses on the different types of scaffolds that have been designed, developed, and tested for tissue engineering of blood vessels, including use of stem cells in vascular tissue engineering.

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Mesenchymal stem cells (MSCs) hold potential for the regeneration of damaged tissues in cardiovascular diseases. In this study, we investigated the potential of porcine MSCs to differentiate into endothelial cells (ECs) in-vitro. The cultured bone marrow derived cells were CD11b−CD34−CD44+CD45−CD90+ and showed mesodermal lineage differentiation which are characteristic of MSCs. The MSCs were induced to differentiate into ECs using endothelial growth media (EGM) with and without high concentrations of VEGF (EGM+VEGF; 50ng/ml). The endothelial basal medium (EBM) without growth factors served as the control. The EC differentiation was assessed by the presence of vWF, ability to take up acetylated LDL, in vitro angiogenesis assay, flow cytometry and qPCR of EC markers vWF, VE-cadherin, PECAM-1, CD34, VEGF-R1 and VEGF-R2 after 10days of stimulation. The cells cultured in EGM+VEGF media demonstrated higher amount of DiI-AcLDL positive cells, and enhanced presence of vWF (90%), VE-Cadherin (60%) and PECAM-1 (48%) positive cells, than in EBM. These cells showed profuse sprouting of capillary tubes and closed polygon formation in the angiogenesis assay. There was 1.5–2 fold increase in the mRNA expression of endothelial markers in the cells stimulated with EGM+VEGF media when compared to control. The results demonstrate the ability of porcine MSCs to differentiate into ECs under in-vitro inducing conditions. The differentiated cells would provide new options for re-endothelialization following interventional procedures and tissue engineering.

Mesenchymal stem cell therapy show great optimism in the treatment of several diseases. MSCs are attractive candidates for cell therapy because of easy isolation, high expansion potential giving unlimited pool of transplantable cells, low immunogenicity, amenability to ex vivo genetic modification, and multipotency. The stem cells orchestrate the repair process by various mechanisms such as transdifferentiation, cell fusion, microvesicles or exosomes and most importantly by secreting paracrine factors. The MSCs release several angiogenic, mitogenic, anti-apoptotic, anti-inflammatory and anti-oxidative factors that play fundamental role in regulating tissue repair in various vascular and cardiac diseases. The therapeutic release of these factors by the cells can be enhanced by several strategies like genetic modification, physiological and pharmacological preconditioning, improved cell culture and selection methods, and biomaterial based approaches. The current review describes the impact of paracrine factors released by MSCs on vascular repair and regeneration in myocardial infarction, restenosis and peripheral artery disease, and the various strategies adopted to enhance the release of these paracrine factors to enhance organ function.

Collectively, based on the remarkable antimicrobial effects, cell-friendly, and stain-free properties, our data suggest that CLIN-m triple antibiotic nanofibers might be a viable alternative to minocycline-based antibiotic pastes.