creation-cardiac-tissue-exhibiting-mechanical-integration-spheroids

Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and ...

Johns Hopkins Hospital

The low arterial oxygen saturation (SaO2) after bidirectional cavopulmonary shunt (BCPS) predicts poor prognosis. The venous oxygen saturation of inferior vena cava (SivcO2), as well as the pulmonary blood flow/systemic blood flow ratio (Q p/Q s) affects the SaO2. The purpose of this study is to determine whether SivcO2 or Q p/Q s should be increased to achieve better outcomes after BCPS. Forty-eight patients undergoing BCPS were included. Data of patients' age and body weight, SivcO2, Q p/Q s, pulmonary artery (PA) pressure and resistance, PA area index, morphology of ventricle, atrioventricular valve regurgitation, and history of PA plasty were collected. Stepwise multiple logistic regression analyses were used to investigate which of the factors most affected the SaO2 after BCPS. There was a significant correlation between SivcO2 and SaO2 (r = 0.771, P < 0.00001). There was no strong correlation between Q p/Q s and SaO2 (r = 0.358, P < 0.05). Stepwise multiple logistic regression analyses revealed that both SivcO2 (r = 0.49, 95 % confidence interval (CI) 0.37-0.62, P < 0.0001) and Q p/Q s (r = 11.1, 95 % CI 3.3-18.9, P = 0.007) most affected SaO2 after BCPS. Since the SivcO2 has a stronger correlation than Q p/Q s with SaO2, despite the fact that both raising Q p/Q s and raising cardiac output can increase SaO2, raising cardiac output should be considered prior to Q p/Q s to raise the SaO2 after BCPS.

Increased systemic cardiac output improves arterial oxygen saturation in bidirectional cavopulmonary shunt.

Tissue engineered vascular grafts (TEVGs) have the potential to overcome the issues faced by existing small diameter prosthetic grafts by providing a biodegradable scaffold where the patient's own cells can engraft and form functional neotissue. However, applying classical approaches to create arterial TEVGs using slow degrading materials with supraphysiological mechanical properties, typically results in limited host cell infiltration, poor remodeling, stenosis, and calcification. The purpose of this study is to evaluate the feasibility of novel small diameter arterial TEVGs created using fast degrading material. A 1.0mm and 5.0mm diameter TEVGs were fabricated with electrospun polycaprolactone (PCL) and chitosan (CS) blend nanofibers. The 1.0mm TEVGs were implanted in mice (n = 3) as an unseeded infrarenal abdominal aorta interposition conduit., The 5.0mm TEVGs were implanted in sheep (n = 6) as an unseeded carotid artery (CA) interposition conduit. Mice were followed with ultrasound and sacrificed at 6 months. All 1.0mm TEVGs remained patent without evidence of thrombosis or aneurysm formation. Based on small animal outcomes, sheep were followed with ultrasound and sacrificed at 6 months for histological and mechanical analysis. There was no aneurysm formation or calcification in the TEVGs. 4 out of 6 grafts (67%) were patent. After 6 months in vivo, 9.1 ± 5.4% remained of the original scaffold. Histological analysis of patent grafts demonstrated deposition of extracellular matrix constituents including elastin and collagen production, as well as endothelialization and organized contractile smooth muscle cells, similar to that of native CA. The mechanical properties of TEVGs were comparable to native CA. There was a significant positive correlation between TEVG wall thickness and CD68+ macrophage infiltration into the scaffold (R2 = 0.95, p = 0.001). The fast degradation of CS in our novel TEVG promoted excellent cellular infiltration and neotissue formation without calcification or aneurysm. Modulating host macrophage infiltration into the scaffold is a key to reducing excessive neotissue formation and stenosis.

Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL/Chitosan Scaffolds in a Sheep Model.

Tissue-engineered vascular grafts (TEVGs) offer potential to overcome limitations of current approaches for reconstruction in congenital heart disease by providing biodegradable scaffolds on which autologous cells proliferate and provide physiologic functionality. However, current TEVGs do not address the diverse anatomic requirements of individual patients. This study explores the feasibility of creating patient-specific TEVGs by combining 3-dimensional (3D) printing and electrospinning technology.

Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model.

Conventional synthetic vascular grafts are limited by the inability to remodel, as well as issues of patency at smaller diameters. Tissue-engineered vascular grafts (TEVGs), constructed from biologically active cells and biodegradable scaffolds have the potential to overcome these limitations, and provide growth capacity and self-repair. Areas covered: This article outlines the TEVG design, biodegradable scaffolds, TEVG fabrication methods, cell seeding, drug delivery, strategies to reduce wait times, clinical trials, as well as a 5-year view with expert commentary. Expert commentary: TEVG technology has progressed significantly with advances in scaffold material and design, graft design, cell seeding and drug delivery. Strategies have been put in place to reduce wait times and improve 'off-the-shelf' capability of TEVGs. More recently, clinical trials have been conducted to investigate the clinical applications of TEVGs.

Tissue engineered vascular grafts: current state of the field.

Electrospinning is a promising technology that provides biodegradable nanofiber scaffolds for cardiovascular tissue engineering. However, success with these materials has been limited, and the optimal combination of scaffold parameters for a tissue-engineered vascular graft (TEVG) remains elusive. The purpose of the present study is to evaluate the effect of bone marrow mononuclear cell (BM-MNC) seeding in electrospun scaffolds to support the rational design of optimized TEVGs.

Article	Year
Increased systemic cardiac output improves arterial oxygen saturation in bidirectional cavopulmonary shunt. Heart and vessels\| PubMed ID: 24213974	2015
Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL/Chitosan Scaffolds in a Sheep Model. PloS one\| PubMed ID: 27467821	2016
Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. The Journal of thoracic and cardiovascular surgery\| PubMed ID: 27938900	2017
Tissue engineered vascular grafts: current state of the field. Expert review of medical devices\| PubMed ID: 28447487	2017
Role of Bone Marrow Mononuclear Cell Seeding for Nanofiber Vascular Grafts. Tissue engineering. Part A\| PubMed ID: 28486019	2017

Takuma Fukunishi

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