Recent Advancements in 3D Printing and Bioprinting Methods for Cardiovascular Tissue Engineering

Recent decades have seen a plethora of regenerating new tissues in order to treat a multitude of cardiovascular diseases. Autografts, xenografts and bioengineered extracellular matrices have been employed in this endeavor. However, current limitations of xenografts and exogenous scaffolds to acquire sustainable cell viability, anti-inflammatory and non-cytotoxic effects with anti-thrombogenic properties underline the requirement for alternative bioengineered scaffolds. Herein, we sought to encompass the methods of biofabricated scaffolds via 3D printing and bioprinting, the biomaterials and bioinks recruited to create biomimicked tissues of cardiac valves and vascular networks. Experimental and computational designing approaches have also been included. Moreover, the in vivo applications of the latest studies on the treatment of cardiovascular diseases have been compiled and rigorously discussed.

BLOOD CYSTS OF THE CARDIAC VALVES IN ADULTS Review and analysis of published cases

Background and aim of the study: Blood cysts of cardiac valves are generally seen in newborns and infants and very rarely in adults. Although in most cases they are incidental findings they may be associated to severe cardiac or systemic complications. This study analyzes incidence, presentation and treatment of valvular blood cysts in adults. Methods: A review of the pertinent literature through a search mainly on PubMed and Medline was performed. Results: In patients ≥ 18 years of age, our search disclosed 54 patients with mitral blood cysts (mean age, 48±18 years), 9 with a tricuspid valve cyst (mean age, 67±15 years), 3 with a blood cyst on the pulmonary valve (age 31, 43 and 44 years) and 1 aortic valve cyst in a 22-year-old man. Most patients were asymptomatic while stroke, syncope or myocardial infarction occurred in 6 patients with a mitral valve cyst. Blood cysts were removed surgically in 70% of patients with a mitral cyst, in 55% with a tricuspid cyst and in all those with a pulmonary or aortic cyst. At histology the cyst wall was composed mainly by fibrous tissue and with the inner surface lined with typical endothelium. Conclusions: Blood cysts of cardiac valves are rare in adults but may cause life-threatening complications particularly when located on the mitral valve. For such reason surgical removal appears advisable, with low-risk procedures. Widespread use of multimodality imaging techniques will most likely increase the number of valvular blood cysts diagnosed also in adults.

Abstract MP235: PROX1 Contributes To Cardiac Valve Disease

Background: Heart valves regulate the unidirectional forward flow and prevent retrograde backflow of blood during the cardiac cycle. Cardiac valve disease (CVD) is observed in approximately 2.5% of the general population and the incidence increases to ~10% in elderly people. Patients with severe CVD require surgery and effective pharmacological treatments are currently not available. PROX1 is a transcription factor that regulates the development of lymphatic, venous, and lymphovenous valves (vascular valves). We identified that PROX1 is also expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 regulates cardiac valve development and disease is not known. Method and Results: We have discovered that mice lacking Prox1 in their VECs ( Prox1 ΔVEC ) develop enlarged aortic and mitral valves in which the expression of proteoglycans is increased (control, N=10; Prox1 ΔVEC , N=9, p <0.05). Echocardiography revealed moderate to severe stenosis of aortic valves of Prox1 ΔVEC mice (control, N=5; Prox1 ΔVEC , N=9, p <0.05). PROX1 regulates the expression of the transcription factor FOXC2 in the vascular valves. Similarly, we have found that the expression of FOXC2 is downregulated in the VECs of Prox1 ΔVEC mice. Specific knockdown of FOXC2 in VECs results in the thickening of aortic valves (control, N=10; shFoxc2 ΔVEC , N=8, p <0.05). Furthermore, restoration of FOXC2 expression in VECs ( Foxc2 OE-VEC ) ameliorates the thickening of the aortic valves of Prox1 ΔVEC mice ( Prox1 ΔVEC , N=9; Foxc2 OE-VEC ; Prox1 ΔVEC , N=8, p <0.05). We have also determined that the expression of platelet-derived growth factor-B ( Pdgfb ) is increased in the valve tissue of Prox1 ΔVEC mice and in PROX1 deficient sheep mitral valve VECs (MVECs) (siCtrl , N=4; siProx1 , N=4, p <0.05). Additionally, hyperactivation of PDGF-B signaling in mice results in a phenotype that is similar to Prox1 ΔVEC mice (control , N=4; Pdgfb GOF , N=3, p <0.05). Conclusion: Together these data suggest that PROX1 maintains the extracellular matrix composition of cardiac valves by regulating the expressions of FOXC2 and PDGF-B in VECs.

A Case of Blunt Chest Trauma and Delayed Severe Tricuspid Regurgitation

Blunt chest trauma could lead to the cardiac valves damage. Flail anterior leaflet with severe tricuspid regurgitation is usually due to blunt chest trauma. This condition is very rare and can lead to deformation and failure of the right ventricle. The tricuspid regurgitation is usually easily diagnosed with transthoracic echocardiography. In this study, we want to present a case with delayed tricuspid damage following blunt chest trauma.

Marantic Endocarditis Associated with COVID-19: A Rare Case Report of a Potentially Deadly Disease

Coronavirus disease 2019 (COVID-19) has overwhelmed healthcare globally with millions of cases and over 2 million deaths worldwide. The hypercoagulable state associated with COVID-19 is a well-recognized complication that carries a poor prognosis. Marantic endocarditis, or non-bacterial thrombotic endocarditis (NBTE), is caused by a sterile vegetation on the cardiac valves resulting from the deposition of fibrin and platelet aggregates. It is highly associated with the hypercoagulable and acquired inflammatory states. Herein, we report a unique and rare case of COVID-19 presenting with NBTE.

Case Report: Isolated and Focal Non-necrotizing Granulomatous Inflammation of Mitral Valves: A Report of Two Cases

Cardiac valve inflammation is seen in the setting of autoimmune or infectious processes, and rarely is valvulitis characterized by granulomatous inflammation. We present two patients who underwent surgical repair of prolapsing/regurgitating mitral valves. Excised valve tissue in both cases revealed commonly encountered nodular fibrosis and calcification, however each also revealed an isolated focus of non-necrotizing granulomatous inflammation. Typical implicating etiologies for non-necrotizing granulomatous inflammation were not present for either patient based on clinical history, or radiologic and laboratory data. In a review of 1048 cardiac valves excised at our institution, the finding of non-necrotizing granulomatous inflammation was seen in only the two described cases (prevalence of 0.19%). The description of non-necrotizing granulomatous inflammation within cardiac valves is limited in the literature, and the significance of the detailed isolated and incidental finding is unclear and requiring further investigation.