Striving for physiologic coaptation: An experimental and innovative approach towards designing and implanting aortic neo-leaflets.

Aortic valve repair has emerged as the treatment of choice for congenital aortic valvular disease, avoiding the need for a reoperation associated with stented prosthesis overgrowth. The introduction of a leaflet implant represents a recent advancement in a field that originated early techniques, such as simple commissurotomies. In our experimental approach, we assessed two established leaflet-sizing techniques by analysing their resultant coaptation areas. Although both techniques produced competent valves, the large coaptation areas differed significantly from the native aortic valve. This observation prompted us to revisit the functional anatomy of the aortic valve, our goal being to refine leaflet design and implantation for enhanced efficacy and longevity in neo-leaflet procedures. We designed a novel aortic valvar neo-leaflet, utilizing porcine pericardium as our primary source material, and we implanted four tri-leaflet valves in four porcine hearts. All tri-leaflet valves were competent and closely resembled the coaptation area of the native aortic valve. This study serves as a pilot for further experimental aortic valve repair surgery using neo-leaflet implants.

An intraoperative test device for aortic valve repair.

OBJECTIVE: Aortic valve repair is currently in transition from surgical improvisation to a reproducible operation and an option for many patients with aortic regurgitation. Our research efforts at improving reproducibility include development of methods for intraoperatively testing and visualizing the valve in its diastolic state. METHODS: We developed a device that can be intraoperatively secured in the transected aorta allowing the aortic root to be pressurized and the closed valve to be inspected endoscopically. Our device includes a chamber that can be pressurized with crystalloid solution and ports for introduction of an endoscope and measuring gauges. We show use of the device in explanted porcine hearts to visualize the aortic valve and to measure leaflet coaptation height in normal valves and in valves that have undergone valve repair procedures. RESULTS: The procedure of introducing and securing the device in the aorta, pressurizing the valve, and endoscopically visualizing the closed valve is done in less than 1 minute. The device easily and reversibly attaches to the aortic root and allows direct inspection of the aortic valve under conditions that mimic diastole. It enables the surgeon to intraoperatively study the valve immediately before repair to determine mechanisms of incompetence and immediately after the repair to assess competence. We also show its use in measuring valve leaflet coaptation height in the diastolic state. CONCLUSIONS: This device enables more relevant prerepair valve assessment and also enables a test of postrepair valve competence under physiological pressures.

In vivo tissue regeneration with robotic implants.

Robots that reside inside the body to restore or enhance biological function have long been a staple of science fiction. Creating such robotic implants poses challenges both in signaling between the implant and the biological host, as well as in implant design. To investigate these challenges, we created a robotic implant to perform in vivo tissue regeneration via mechanostimulation. The robot is designed to induce lengthening of tubular organs, such as the esophagus and intestines, by computer-controlled application of traction forces. Esophageal testing in swine demonstrates that the applied forces can induce cell proliferation and lengthening of the organ without a reduction in diameter, while the animal is awake, mobile, and able to eat normally. Such robots can serve as research tools for studying mechanotransduction-based signaling and can also be used clinically for conditions such as long-gap esophageal atresia and short bowel syndrome.

An Intracardiac Soft Robotic Device for Augmentation of Blood Ejection from the Failing Right Ventricle.

We introduce an implantable intracardiac soft robotic right ventricular ejection device (RVED) for dynamic approximation of the right ventricular (RV) free wall and the interventricular septum (IVS) in synchrony with the cardiac cycle to augment blood ejection in right heart failure (RHF). The RVED is designed for safe and effective intracardiac operation and consists of an anchoring system deployed across the IVS, an RV free wall anchor, and a pneumatic artificial muscle linear actuator that spans the RV chamber between the two anchors. Using a ventricular simulator and a custom controller, we characterized ventricular volume ejection, linear approximation against different loads and the effect of varying device actuation periods on volume ejection. The RVED was then tested in vivo in adult pigs (n = 5). First, we successfully deployed the device into the beating heart under 3D echocardiography guidance (n = 4). Next, we performed a feasibility study to evaluate the device's ability to augment RV ejection in an experimental model of RHF (n = 1). RVED actuation augmented RV ejection during RHF; while further chronic animal studies will provide details about the efficacy of this support device. These results demonstrate successful design and implementation of the RVED and its deployment into the beating heart. This soft robotic ejection device has potential to serve as a rapidly deployable system for mechanical circulatory assistance in RHF.

Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion.

OBJECTIVE: To demonstrate the clinical efficacy of autologous mitochondrial transplantation in preparation for translation to human application using an in vivo swine model. METHODS: A left mini-thoracotomy was performed on Yorkshire pigs. The pectoralis major was dissected, and skeletal muscle tissue was removed and used for the isolation of autologous mitochondria. The heart was subjected to regional ischemia (RI) by temporarily snaring the circumflex artery. After 24 minutes of RI, hearts received 8 × 0.1 mL injections of vehicle (vehicle-only group; n = 6) or vehicle containing mitochondria (mitochondria group; n = 6) into the area at risk (AAR), and the snare was released. The thoracotomy was closed, and the pigs were allowed to recover for 4 weeks. RESULTS: Levels of creatine kinase-MB isoenzyme and cardiac troponin I were significantly increased (P = .006) in the vehicle-only group compared with the mitochondria group. Immune, inflammatory, and cytokine activation markers showed no significant difference between groups. There was no significant between-group difference in the AAR (P = .48), but infarct size was significantly greater in the vehicle group (P = .004). Echocardiography showed no significant differences in global function. Histochemistry and transmission electron microscopy revealed damaged heart tissue in the vehicle group that was not apparent in the mitochondria group. T2-weighted magnetic resonance imaging and histology demonstrated that the injected mitochondria were present for 4 weeks. CONCLUSIONS: Autologous mitochondrial transplantation provides a novel technique to significantly enhance myocardial cell viability following ischemia and reperfusion in the clinically relevant swine model.

Cardioscopic Tool-delivery Instrument for Beating-heart Surgery.

This paper describes an instrument that provides solutions to two open challenges in beating-heart intracardiac surgery - providing high-fidelity imaging of tool-tissue contact and controlling tool penetration into tissue over the cardiac cycle. Tool delivery is illustrated in the context of tissue removal for which these challenges equate to visualization of the tissue as it is being removed and to control of cutting depth. Cardioscopic imaging is provided by a camera and illumination system encased in an optical window. When the optical window is pressed against tissue, it displaces the blood between the camera and tissue allowing clear visualization. Control of cutting depth is achieved via precise extension of the cutting tool from a port in the optical window. Successful tool use is demonstrated in ex vivo and in vivo experiments.

Surgical repair of congenital aortic regurgitation by aortic root reduction: A finite element study.

During surgical reconstruction of the aortic valve in the child, the use of foreign graft material can limit durability of the repair due to inability of the graft to grow with the child and to accelerated structural degeneration. In this study we use computer simulation and ex vivo experiments to explore a surgical repair method that has the potential to treat a particular form of congenital aortic regurgitation without the introduction of graft material. Specifically, in an aortic valve that is regurgitant due to a congenitally undersized leaflet, we propose resecting a portion of the aortic root belonging to one of the normal leaflets in order to improve valve closure and eliminate regurgitation. We use a structural finite element model of the aortic valve to simulate the closed, pressurized valve following different strategies for surgical reduction of the aortic root (e.g., triangular versus rectangular resection). Results show that aortic root reduction can improve valve closure and eliminate regurgitation, but the effect is highly dependent on the shape and size of the resected region. Only resection strategies that reduce the size of the aortic root at the level of the annulus produce improved valve closure, and only the strategy of resecting a large rectangular portion-extending the full height of the root and reducing root diameter by approximately 12% - is able to eliminate regurgitation and produce an adequate repair. Ex vivo validation experiments in an isolated porcine aorta corroborate simulation results.

High level expression of bioactive recombinant human growth hormone in the milk of a cloned transgenic cow.

Transgenic farm animals have been proposed as an alternative to current bioreactors for large scale production of biopharmaceuticals. However, the efficiency of both methods in the production of the same protein has not yet been established. Here we report the production of recombinant human growth hormone (hGH) in the milk of a cloned transgenic cow at levels of up to 5 g l(-1). The hormone is identical to that currently produced by expression in E. coli. In addition, the hematological and somatometric parameters of the cloned transgenic cow are within the normal range for the breed and it is fertile and capable of producing normal offspring. These results demonstrate that transgenic cattle can be used as a cost-effective alternative for the production of this hormone.