Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs. However, after more than a decade of incubation and many proofs of concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those that followed, were modified versions of the three-dimensional printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, microextrusion, or laser assisted), this approach is material (“scaffold”) dependent and energy intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler scaffold-free bioassembling methods. A substantial body of evidence has accumulated, indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone, and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely “print” spheroids has not been available until the invention of the microneedles-based (“Kenzan”) spheroid assembling and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel microneedles (“kenzans”) as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bioengineering of tissues and organs

Single center experience on dosing and adverse events of recombinant factor seven use for bleeding after congenital heart surgery

There are limited data on the relationship between the administered dose of recombinant factor seven (rFVIIa) and the development of adverse clinical outcomes after congenital heart surgery. This single institution case series reports on dosing, adverse events, and blood product usage after the administration of rFVIIa in the congenital heart surgery patient population. A retrospective review identified 16 consecutive pediatric patients at an academic, free-standing, children’s hospital who received rFVIIa to curtail bleeding following congenital heart surgery between April 2004 and June 2012. Patients were assessed for survival to hospital discharge versus in-hospital mortality and the presence or absence of a major neurological event during inpatient hospitalization. The median age at surgery was 6.8 months (range: 3 days–42 years). Seven patients (44%) survived to hospital discharge and nine patients (56%) died. The cause of mortality included major neurological events (44%), uncontrolled bleeding (33%), and sepsis (23%). Eight patients (50%) required extracorporeal membrane oxygenation support following congenital heart surgery. The median cumulative rFVIIa dose administered was 97 mcg/kg, and the median cumulative amount of blood products administered was 452 ml/kg. In conclusion, this case series underscores the need to prospectively evaluate the effect that rFVIIa has on patient survival and the incidence of adverse events, including thrombotic and major neurological events, in congenital heart surgery patients. Ideally, a randomized, multicenter study would provide the sufficient numbers of patients and events to test these relationships

Designing Customized 3D Printed Models for Surgical Planning in Repair of Congenital Heart Defects

Advances in diagnostic imaging and 3D printing technologyhave enabled the creation of patient-specic models. Thisresearch established a wor kow for creating 3D printedcongenital hear t defec t (CHD) models, focusing specically oncreating aor tic arch models optimized for surgical planning andsimulation for hypoplastic left hear t syndrome (HLHS) stage Ipalliation. Novel methods for creating C T as well as 3Dultrasound and 3D fetal ultrasound derived prints were explored

Cardiac tissue engineering for the treatment of hypoplastic left heart syndrome (HLHS)

Hypoplastic left heart syndrome (HLHS) is a deadly congenital heart disease that arises when the left ventricle and outflow tract fail to develop appropriately, inhibiting the adequate perfusion of the rest of the body. Historically, this disease has been treated via a series of surgeries that allows the heart to use a single ventricle. These surgeries are often a palliative measure, and heart transplantation is the only definitive therapy that exists for this condition. It has been hypothesized that stem cell-based regenerative therapies could have a role in promoting cardiac tissue regeneration in HLHS patients who are undergoing palliative surgery. Several clinical trials have demonstrated that introducing pluripotent cells into the heart is safe, feasible, and capable of improving right ventricular ejection fraction (RVEF). However, while these approaches show great promise, there is still room for development. There is a substantial body of pre-clinical work that is focused on generating increasingly large and complex pieces of cardiac tissue in the form of cardiac patches, with the idea that these could be used to rebuild and strengthen the heart in a robust and long-lasting manner. In total, stem cell-based therapies have much to offer when it comes to improving the treatment of HLHS

Stem cells and congenital heart disease: The future potential clinical therapy beyond current treatment

Congenital heart disease (CHD) is the most common congenital anomaly in newborns. Current treatment for cyanotic CHD largely relies on the surgical intervention; however, significant morbidity and mortality for patients with CHD remain. Recent research to explore new avenues of treating CHD includes the utility of stem cells within the field. Stem cells have since been used to both model and potentially treat CHD. Most clinical applications to date have focused on hypoplastic left heart syndrome. Here, we examine the current role of stem cells in CHD and discuss future applications within the field