Umbilical Cord Pericytes Provide a Viable Alternative to Mesenchymal Stem Cells for Neonatal Vascular Engineering

Reconstructive surgery of congenital heart disease (CHD) remains inadequate due to the inability of prosthetic grafts to match the somatic growth of pediatric patients. Functionalization of grafts with mesenchymal stem cells (MSCs) may provide a solution. However, MSCs represent a heterogeneous population characterized by wide diversity across different tissue sources. Here we investigated the suitability of umbilical cord pericytes (UCPs) in neonatal vascular engineering. Explant outgrowth followed by immunomagnetic sorting was used to isolate neural/glial antigen 2 (NG2)+/CD31− UCPs. Expanded NG2 UCPs showed consistent antigenic phenotype, including expression of mesenchymal and stemness markers, and high proliferation rate. They could be induced to a vascular smooth muscle cell-like phenotype after exposure to differentiation medium, as evidenced by the expression of transgelin and smooth muscle myosin heavy chain. Analysis of cell monolayers and conditioned medium revealed production of extracellular matrix proteins and the secretion of major angiocrine factors, which conferred UCPs with ability to promote endothelial cell migration and tube formation. Decellularized swine-derived grafts were functionalized using UCPs and cultured under static and dynamic flow conditions. UCPs were observed to integrate into the outer layer of the graft and modify the extracellular environment, resulting in improved elasticity and rupture strain in comparison with acellular grafts. These findings demonstrate that a homogeneous pericyte-like population can be efficiently isolated and expanded from human cords and integrated in acellular grafts currently used for repair of CHD. Functional assays suggest that NG2 UCPs may represent a viable option for neonatal tissue engineering applications.

Swine Disease Models for Optimal Vascular Engineering

Swine disease models are essential for mimicry of human metabolic and vascular pathophysiology, thereby enabling high-fidelity translation to human medicine. The worldwide epidemic of obesity, metabolic disease, and diabetes has prompted the focus on these diseases in this review. We highlight the remarkable similarity between Ossabaw miniature swine and humans with metabolic syndrome and atherosclerosis. Although the evidence is strongest for swine models of coronary artery disease, findings are generally applicable to any vascular bed. We discuss the major strengths and weaknesses of swine models. The development of vascular imaging is an example of optimal vascular engineering in swine. Although challenges regarding infrastructure and training of engineers in the use of swine models exist, opportunities are ripe for gene editing, studies of molecular mechanisms, and use of swine in coronary artery imaging and testing of devices that can move quickly to human clinical studies.

The future application of nanomedicine and biomimicry in plastic and reconstructive surgery

Plastic surgery encompasses a broad spectrum of reconstructive challenges and prides itself upon developing and adopting new innovations. Practice has transitioned from microsurgery to supermicrosurgery with a possible future role in even smaller surgical frontiers. Exploiting materials on a nanoscale has enabled better visualization and enhancement of biological processes toward better wound healing, tumor identification and viability of tissues, all cornerstones of plastic surgery practice. Recent advances in nanomedicine and biomimicry herald further reconstructive progress facilitating soft and hard tissue, nerve and vascular engineering. These lay the foundation for improved biocompatibility and tissue integration by the optimization of engineered implants or tissues. This review will broadly examine each of these technologies, highlighting areas of progress that reconstructive surgeons may not be familiar with, which could see adoption into our armamentarium in the not-so-distant future.

Bioprinting of artificial blood vessels

Vascular networks have an important role to play in transporting nutrients, oxygen, metabolic wastes and maintenance of homeostasis. Bioprinting is a promising technology as it is able to fabricate complex, specific multi-cellular constructs with precision. In addition, current technology allows precise depositions of individual cells, growth factors and biochemical signals to enhance vascular growth. Fabrication of vascularized constructs has remained as a main challenge till date but it is deemed as an important stepping stone to bring organ engineering to a higher level. However, with the ever advancing bioprinting technology and knowledge of biomaterials, it is expected that bioprinting can be a viable solution for this problem. This article presents an overview of the biofabrication of vascular and vascularized constructs, the different techniques used in vascular engineering such as extrusion-based, droplet-based and laser-based bioprinting techniques, and the future prospects of bioprinting of artificial blood vessels.