ABSTRACT
The need to develop wearable devices for personal health monitoring, diagnostics, and therapy has inspired the production of innovative on-demand, customizable technologies. Several of these technologies enable printing of raw electronic materials directly onto biological organs and tissues. However, few of them have been thoroughly investigated for biocompatibility of the raw materials on the cellular, tissue, and organ levels or with different cell types. In addition, highly accurate multiday in vivo monitoring using such on-demand, in situ fabricated devices has yet to be done. Presented herein is the first fully biocompatible, on-skin fabricated electronics for multiple cell types and tissues that can capture electrophysiological signals with high fidelity. While also demonstrating improved mechanical and electrical properties, the drawn-on-skin ink retains its properties under various writing conditions, which minimizes the variation in electrical performance. Furthermore, the drawn-on-skin ink shows excellent biocompatibility with cardiomyocytes, neurons, mice skin tissue, and human skin. The high signal-to-noise ratios of the electrophysiological signals recorded with the DoS sensor over multiple days demonstrate its potential for personalized, long-term, and accurate electrophysiological health monitoring.
Subject(s)
Ink , Wearable Electronic Devices , Animals , Electronics , Electrophysiology , Humans , Mice , SkinABSTRACT
Patients with end-stage congestive heart failure are at elevated risk for harm when extreme storms threaten and strike their communities. Individuals with compromised heart function require customized hurricane protection and preparedness approaches. We provide mitigation strategies for providers and their teams, as well as the patients themselves to ensure their safety and uninterrupted access to healthcare resources and quality care during hurricane impact and in the aftermath.
Subject(s)
Cyclonic Storms , Heart Failure , Climate Change , Heart Failure/therapy , HumansABSTRACT
BACKGROUND: The optimal aortic substitute in extensive aortic valve active infective endocarditis (AIE) continues to be debated. To determine the surgical approach in aortic valve AIE with infection extension beyond the leaflets, we evaluated the outcome of reconstructive surgery with various valve substitutes in those patients. METHODS: During 2000-2013, 168 patients had surgery for extensive aortic valve AIE. Patients were categorised based on aortic valve substitute: Group A: Stented aortic valve replacement (AVR), Group B: Stented AVR with patch support, Group C: Stentless valve, Group D: Aortic allograft, and Group E: Composite valve graft. Outcome parameters were mortality, postoperative cardiogenic or septic shock, stroke, or reinfection. RESULTS: Stented valves with patch support were more frequently utilised in cases of native valve endocarditis (p<0.001). Postoperative complications were comparable among groups. Concomitant preoperative extension of infection in the mitral valve predicted reinfection (OR 3.6; confidence interval 1.46-8.66; p=0.005). Survival was not affected by operative group (log rank=0.6). Univariable preoperative predictors of mortality were: septic shock (hazard ratio 8.3; 95% confidence interval 3.6-19.2; p<0.001), ejection fraction (hazard ratio 0.96; 95% confidence interval 0.93-0.99; p=0.006), preoperative cardiogenic shock (hazard ratio 1.9; 95%CI 1.1-3.6, p=0.02) and concomitant mitral valve surgery (hazard ratio 1.8; 95% confidence interval 1.2-2.5; p=0.002). CONCLUSIONS: Surgical treatment of extensive aortic valve infective endocarditis remains a challenge. Outcomes were not affected by the surgical complexity of aortic reconstruction procedure or valve substitute. Surgical approach should be tailored to individual patient's characteristics.
Subject(s)
Aortic Valve/surgery , Endocarditis/mortality , Endocarditis/surgery , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Postoperative Complications/mortality , Adult , Aged , Aged, 80 and over , Aortic Valve/microbiology , Endocarditis/microbiology , Female , Humans , Male , Middle Aged , Mitral Valve/microbiology , Mitral Valve/surgery , Postoperative Complications/microbiology , Retrospective StudiesABSTRACT
Engineering a bioartificial heart has become a possibility in part because of the regenerative medicine approaches to repairing or replacing damaged organs that have evolved over the past two decades. With the advent of inducible pluripotent stem cell technology, it is now possible to generate personalized cells that make the concept of autologous tissue engineering imaginable. Scaffolds that provide form, function, and biological cues to cells likewise potentially enable the engineering of biocompatible vascularized solid organs. Decellularized organs or tissue matrices retain organ complexity and structure at the macro and micro scales, contain biologically active molecules that support cell phenotype and function, and are vascularized allowing full thickness tissue generation. There is also dynamic reciprocity between the extracellular matrix and cells, which does not occur with synthetic scaffolds and allows both to evolve as functional need changes, making it a unique scaffold. Yet, building a whole heart from decellularized scaffolds and cells requires delivering hundreds of billions of multiple types of cardiac cells appropriately and providing a milieu where they can survive and mature. We propose a novel type of in vivo organ engineering utilizing pre-clinical models where decellularized hearts are heterotopically transplanted with the intent to harness the capability of the body to at least in part repopulate the scaffold. By adding load and electrical input, possibly via temporary mechanical assistance, we posit that vascular and parenchymal cell maturation can occur. In this study, we implanted porcine decellularized hearts acutely and chronically in living recipients in a heterotopic position. We demonstrated that the surgical procedure is critical to prevent coagulation and to increase graft patency. We also demonstrated that short-term implantation promotes endothelial cell adhesion to the vessel lumens and that long-term implantation also promotes tissue formation with evidence of cardiomyocytes and endothelial cells present within the graft. Utilizing endogenous repair capabilities of the recipient in response to a naked ECM, we allowed the transplanted scaffold to direct host cells-both organizationally and functionally. Thus, the scaffold provided necessary cues for cell organization and remodeling within the transplanted organ. Future work would involve culturing partially recellularized engineered organs in bioreactors where mechanical and electrical stimulation can be controlled to promote organ development and then transplanting these after a minimal level of maturation has been achieved.
Subject(s)
Bioartificial Organs , Extracellular Matrix/chemistry , Extracellular Matrix/transplantation , Heart Transplantation/methods , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cattle , Cell Adhesion , Endothelial Cells/cytology , Female , Male , Myocardium/chemistry , Myocardium/cytology , Myocytes, Cardiac/cytology , SwineABSTRACT
OBJECTIVES: In recent years, video-assisted thoracoscopic surgery (VATS) has increasingly become the preferred technique for thoracic surgery. However, the inherent characteristics of the lungs as large, soft, slippery, and delicate creates difficulties for pulmonary surgery. In this article, we outline the development and assessment of a balloon-based organ retractor for VATS via collaboration between medical and engineering personnel. METHODS: A dry lab trial and accompanying questionnaire assessment were performed by a group of thoracic surgeons. Objective pressure measurements were obtained, and animal experiment on pigs was performed. RESULTS: In the dry lab trial, use of the developed organ retractor required significantly less time and resulted in fewer difficulties than using a Cherry Dissector. The measured pressure per mm2 of the developed retractor was clearly lower than that for the Cherry Dissector. The questionnaire completed by the surgeons following the dry lab and animal experiments showed that most of the surgeons (7 surgeons out of 9) were satisfied with the quality of the balloon-based retractor based on a score of 3.13 ± 0.28 (mean ± standard deviation) out of 4.0. During the animal experiment, the balloon-based retractor provided stable and clear viewing with minimal need for adjustment. CONCLUSION: This balloon-based retractor could contribute to increased safety and less-invasive VATS.
Subject(s)
Surgical Instruments , Thoracic Surgery, Video-Assisted/instrumentation , Thoracic Surgery, Video-Assisted/methods , Animals , Biomedical Engineering , Equipment Design , SwineABSTRACT
PURPOSE OF REVIEW: Heart transplantation is the only curative treatment option for end-stage heart failure. However, a shortage of donor organs is a major limitation of this approach. Regenerative medicine targets the goal of increasing the number of available hearts for transplantation. In this review, we highlight the state of the art of building a bioartificial heart. We summarize the components needed, the hurdles, and likely translational steps to make the dream of transplanting a totally functional bioartificial heart a possibility. RECENT FINDINGS: The therapies being developed in regenerative medicine aim not only to repair, but also to regenerate or replace failing tissues and organs. The engineering of bioartificial hearts utilizing patient-derived cells could theoretically solve the two main complications of heart transplantations: graft rejection and lifelong immunosuppression. Although many hurdles remain, scientists have reached a point in which some of these hurdles have been overcome. Decellularized heart scaffolds have emerged over the past decade as one of the most promising biofabrications. Two possible options for organ scaffolds exist: nontransplantable human hearts and porcine hearts. The use of these scaffolds could lead to the availability of an unlimited number of transplantable organs. The current challenge remains improving processes required for recellularization - including those for cells, bioreactors, and physiologic conditioning. Researchers should focus to solve these hurdles and pave the way toward the dream of in-vivo bioengineered heart maturation. SUMMARY: Regenerative medicine has emerged as one of the most promising fields of translational research and has the potential to both minimize the need for donor organs and increase their availability. Meeting the challenge of implanting a totally functional bioengineered heart lies in solving multiple issues simultaneously. Dwarfing the technical hurdles, cost is the largest barrier to success. The scientific hurdles mainly involve scaling up and scaling out of laboratory cell processes, building bioreactors, and delivering cells into every needed region of an organ scaffold. Maintaining sterility and quantifying readiness of the nascent organs are also critical for success.
Subject(s)
Heart Transplantation/methods , Heart/physiopathology , Regenerative Medicine/methods , Tissue Engineering/methods , Animals , Humans , SwineABSTRACT
Heart failure with preserved ejection fraction (HFpEF) is characterized by a complex, heterogeneous spectrum of pathologic features combined with average left ventricular volume and diastolic dysfunction. HFpEF is a significant public health problem associated with high morbidity and mortality rates. Currently, effective treatments for HFpEF represent the greatest unmet need in cardiovascular medicine. A lack of an efficient preclinical model has hampered the development of new devices and medications for HFpEF. Because large animal models have similar physiologic traits as humans and appropriate organ sizes, they are the best option for limiting practical constraints. HFpEF is a highly integrated, multiorgan, systemic disorder requiring a multipronged investigative approach. Here, we review the large animal models of HFpEF reported to date and describe the methods that have been used to create HFpEF, including surgery-induced pressure overloading, medicine-induced pressure overloading, and diet-induced metabolic syndrome. In addition, for the first time to our knowledge, we use two established clinical HFpEF algorithms (HFA-PEFF and H2FPEF scores) to evaluate the currently available large animal models. We also discuss new technologies, such as continuous remote pressure monitors and inflatable aortic cuffs, as well as how the models could be improved. Based on current progress and our own experience, we believe an efficient large animal model of HFpEF should simultaneously encompass multiple pathophysiologic factors, along with multiorgan dysfunction. This could be fully evaluated through available methods (imaging, blood work). Although many models have been studied, only a few studies completely meet clinical score standards. Therefore, it is critical to address the deficiencies of each model and incorporate novel techniques to establish a more reliable model, which will help facilitate the understanding of HFpEF mechanisms and the development of a treatment.
ABSTRACT
Heart rate variability (HRV) is a measurement of the fluctuation of time between each heartbeat and reflects the function of the autonomic nervous system. HRV is an important indicator for both physical and mental status and for broad-scope diseases. In this review, we discuss how wearable devices can be used to monitor HRV, and we compare the HRV monitoring function among different devices. In addition, we have reviewed the recent progress in HRV tracking with wearable devices and its value in health monitoring and disease diagnosis. Although many challenges remain, we believe HRV tracking with wearable devices is a promising tool that can be used to improve personal health.
Subject(s)
Wearable Electronic Devices , Heart Rate/physiology , Autonomic Nervous System/physiology , Monitoring, Physiologic , Heart Rate DeterminationABSTRACT
OBJECTIVES: Previous studies show that the distal transradial approach (dTRA) is safe and effective for coronary angiography and percutaneous coronary intervention. However, the effect of dTRA on radiation exposure in the catheterization laboratory has not been characterized. The authors analyzed the available literature to compare the radiation exposure associated with dTRA vs the traditional radial approach (TRA). METHODS: A systematic review and meta-analysis of the scientific literature was conducted by using relevant terms to search the PubMed, Embase, and Cochrane Library databases from their inception until October 13, 2022, to identify randomized controlled trials (RCTs) comparing dTRA with TRA. The primary outcome was radiation exposure reported as fluoroscopy time, air kerma, or kerma-dose product. The standard mean difference (SMD) and its 95% confidence interval were used to summarize continuous variables. Random effect and meta-regression also were used for analyses. RESULTS: Among 484 studies identified, 7 were RCTs, with a total of 3427 patients (1712 dTRA, 1715 TRA). No difference was found between dTRA and TRA in radiation exposure quantified as fluoroscopy time (SMD -0.10 [-0.36, 0.15], P=.43) or air kerma (SMD -0.31 [-0.74, 0.13], P=.17). The overall estimate favored lower kerma-area product in the TRA (SMD 0.19 [0.08, 0.30], P=.0006). Meta-regression showed no correlation between fluoroscopy time and year of publication. CONCLUSIONS: Compared with TRA, dTRA was associated with significantly greater radiation exposure per the kerma-area product during interventional cardiology procedures, with no differences in fluoroscopy time and air kerma.
Subject(s)
Percutaneous Coronary Intervention , Radiation Exposure , Humans , Coronary Angiography/adverse effects , Coronary Angiography/methods , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Randomized Controlled Trials as Topic , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Radiation Exposure/adverse effects , Radiation Exposure/prevention & control , Radial ArteryABSTRACT
We examined the changes in variables that could be recorded on wearable devices during the early stages of acute myocardial infarction (AMI) in an animal model. Early diagnosis of AMI is important for prognosis; however, delayed diagnosis is common because of patient hesitation and lack of timely evaluations. Wearable devices are becoming increasingly sophisticated in the ability to track indicators. In this study, we retrospectively reviewed the changes in four variables during AMI in a pig model to assess their ability to help predict AMI onset. AMI was created in 33 pigs by 90-min balloon occlusion of the left anterior descending artery. Blood pressure, EKG, and lactate and cardiac troponin I levels were recorded during the occlusion period. Blood pressure declined significantly within 15 min after balloon inflation (mean arterial pressure, from 61 ± 8 to 50 ± 8 mmHg) and remained at this low level. Within 5 min of balloon inflation, the EKG showed ST-elevation in precordial leads V1-V3. Blood lactate levels increased gradually after occlusion and peaked at 60 min (from 1.48 to 2.53 mmol/L). The continuous transdermal troponin sensor demonstrated a gradual increase in troponin levels over time. Our data suggest that significant changes in key indicators (blood pressure, EKG leads V1-V3, and lactate and troponin levels) occurred at the onset of AMI. Monitoring of these variables could be used to develop an algorithm and alert patients early at the onset of AMI with the help of a wearable device.
ABSTRACT
Although the outcome after myocardial infarction depends on the time to treatment, a delay between symptom onset and treatment is common. Apple Watch, a popular wearable device, provides the ability to perform an electrocardiogram. We review the progress made in using the Apple Watch to record multiple electrocardiogram leads for diagnosing myocardial infarction. Although the data are encouraging, many limitations remain, and more research is needed. Nevertheless, the Apple Watch could eventually serve as a self-check tool for patients who have chest pains or other symptoms of myocardial infarction, thus substantially decreasing the time to treatment and improving the outcome after myocardial infarction.
Subject(s)
Myocardial Infarction , Wearable Electronic Devices , Chest Pain , Electrocardiography , Humans , Myocardial Infarction/diagnosisABSTRACT
Congestive heart failure (HF) is a devastating disease leading to prolonged hospitalization, high morbidity and mortality rates, and increased costs. Well-established treatments for decompensated or unstable patients include medications and mechanical cardiac support devices. For acute HF decompensation, new devices are being developed to help relieve symptoms and recover heart and renal function in these patients. A recent device-based classification scheme, collectively classified as DRI2P2S, has been proposed to better describe these new device-based therapies based on their mechanism: dilators (increase venous capacitance), removers (direct removal of sodium and water), inotropes (increase left ventricular contractility), interstitials (accelerate removal of lymph), pushers (increase renal arterial pressure), pullers (decrease renal venous pressure), and selective (selective intrarenal drug infusion). In this review, we describe the new class of medical devices with the most current results reported in preclinical models and clinical trials.
ABSTRACT
OBJECTIVE: Delayed cardiac tamponade, a life-threatening complication of pericardial effusion in humans, has rarely been described in large animal models. We report here a pig with cardiac tamponade that developed 29 days after cardiac surgery. STUDY DESIGN: Case report. ANIMALS: One 45-kg domestic pig. METHODS: Open-chest surgery was performed on a pig to induce chronic heart failure. At 15 days after surgery, the pig's breathing appeared laboured; induced heart failure was considered the cause. Routine heart failure medications were administered. RESULTS: On day 28, the pig's status deteriorated. On day 29, echocardiography performed just before the pig's death showed a large pericardial effusion, mainly in the lateral and anterior walls of the right heart, with several fibre exudation bands. The right heart was severely compressed with an extremely small right ventricle. An emergency sternotomy was unsuccessful. Pathologic examination showed a severely thickened, fibrous pericardium. The pericardial sac was distended (up to 4.5 cm) and was full of dark brown, soft, friable material. Epicardial haemorrhage with a fresh, organised thrombus was noted in the pericardium. CONCLUSION: Delayed tamponade occurring at least 15 days after open-chest surgery is easy to misdiagnose or overlook in large animal models where attention is often focused on primary pathological model changes. To decrease mortality in animal models, researchers should be aware of potential complications and use the same level of follow-up monitoring of large animals as in clinical care.
Subject(s)
Cardiac Surgical Procedures , Cardiac Tamponade , Heart Failure , Pericardial Effusion , Swine Diseases , Animals , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/veterinary , Cardiac Tamponade/diagnosis , Cardiac Tamponade/etiology , Cardiac Tamponade/veterinary , Heart Failure/complications , Heart Failure/pathology , Heart Failure/veterinary , Humans , Pericardial Effusion/diagnosis , Pericardial Effusion/etiology , Pericardial Effusion/surgery , Pericardial Effusion/veterinary , Pericardium/pathology , SwineABSTRACT
Left ventricular assist devices (LVADs) have increasingly been used clinically to treat heart failure patients. However, hemolysis, pump thrombosis, infection and bleeding still persist as major limitations of LVAD technology. Assessing LVAD hemocompatibility using a blood shear stress device (BSSD) has clear advantages, as the BSSD could provide a better experimental platform to develop reliable, quantifiable blood trauma assays to perform iterative testing of LVAD designs. In this study, a BSSD was proposed with short blood exposure time and no seals or contact bearings to reduce blood trauma caused by the test platform. Enlarged air-gap drive motor in BSSD is essential to avoid high shear stress; however, it would significantly reduce the motor torque, which may result in inadequate force to drive the entire system. In order to evaluate and optimize the drive motor air-gap to ensure adequate motor torque as well as acceptable range for blood exposure time and shear stress, a numerical brushless DC (BLDC) motor model was established using finite element method (FEM) in numerical simulation software COMSOL. The model was first validated by the experimental results. Then numerical model with different air-gap was evaluated on the torque and speed constant changes. In the end, two equations were generated based on the curves derived from the torque and speed constant calculations. Determining these relationships between motor performance and motor air-gap will facilitate the development of an appropriate BLDC motor size for the BSSD, considering the design limitations in our future work.
Subject(s)
Heart Failure , Heart-Assist Devices , Animals , Hemolysis , Humans , Stress, Mechanical , TorqueABSTRACT
Left ventricular assist devices (LVADs) are used to treat patients with severe (New York Heart Association class IV) heart failure. Thrombosis and bleeding are severe LVAD-related complications; thus, an effective anticoagulation regimen is crucial for successful postoperative management. The CH-VAD™ (CH Biomedical, Inc.) is a small, implantable, full-support (>5 L/min) LVAD with a centrifugal flow pump that has a fully magnetically levitated rotor, which confers superior hemocompatibility. In this study, the CH-VAD™ was implanted in two calves to evaluate its hemocompatibility and to establish an anticoagulation regimen for future GLP (good laboratory practice) studies. Heparin infusion was used during the surgery, and during postoperative management, the proper dosage of warfarin was given orally to maintain an international normalized ratio (INR) between 2.0 and 3.0. Pump performance, animal condition, and hematology results were recorded throughout the study (approximately 60 days). The results show that under the established anticoagulation regimen, the CH-VAD™ was well tolerated in the bovine model, with no significant thrombus or thromboembolic lesion formation in distal end organs. Low plasma free hemoglobin levels suggest that the device did not cause hemolysis. These results and the experience gained pave the way for future GLP studies.
Subject(s)
Heart Failure , Heart-Assist Devices , Thrombosis , Animals , Cattle , Hemodynamics , Humans , WarfarinABSTRACT
Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12-week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.
Subject(s)
Esophagus/metabolism , Guided Tissue Regeneration/methods , Tissue Engineering/methods , Animals , Cell Differentiation/physiology , Human Umbilical Vein Endothelial Cells , Humans , Male , Mesenchymal Stem Cells/cytology , Myocytes, Smooth Muscle/cytology , Printing, Three-Dimensional , Rats , Rats, Inbred F344 , Regeneration/physiology , Tissue Scaffolds/chemistry , Vascular Endothelial Growth Factor AABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0211339.].
ABSTRACT
BACKGROUND: Impaired myocardial conduction is the underlying mechanism for re-entrant arrhythmias. Carbon nanotube fibers (CNTfs) combine the mechanical properties of suture materials with the conductive properties of metals and may form a restorative solution to impaired myocardial conduction. METHODS: Acute open chest electrophysiology studies were performed in sheep (n=3). Radiofrequency ablation was used to create epicardial conduction delay after which CNTf and then silk suture controls were applied. CNTfs were surgically sewn across the right atrioventricular junction in rodents, and acute (n=3) and chronic (4-week, n=6) electrophysiology studies were performed. Rodent toxicity studies (n=10) were performed. Electrical analysis of the CNTf-myocardial interface was performed. RESULTS: In all cases, the large animal studies demonstrated improvement in conduction velocity using CNTf. The acute rodent model demonstrated ventricular preexcitation during sinus rhythm. All chronic cases demonstrated resumption of atrioventricular conduction, but these required atrial pacing. There was no gross or histopathologic evidence of toxicity. Ex vivo studies demonstrated contact impedance significantly lower than platinum iridium. CONCLUSIONS: Here, we show that in sheep, CNTfs sewn across epicardial scar acutely improve conduction. In addition, CNTf maintain conduction for 1 month after atrioventricular nodal ablation in the absence of inflammatory or toxic responses in rats but only in the paced condition. The CNTf/myocardial interface has such low impedance that CNTf can facilitate local, downstream myocardial activation. CNTf are conductive, biocompatible materials that restore electrical conduction in diseased myocardium, offering potential long-term restorative solutions in pathologies interrupting efficient electrical transduction in electrically excitable tissues.
Subject(s)
Arrhythmias, Cardiac/surgery , Atrioventricular Node/physiopathology , Carbon Fiber , Catheter Ablation/methods , Heart Atria/physiopathology , Myocardium/pathology , Nanotubes, Carbon , Animals , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/physiopathology , Atrioventricular Node/surgery , Disease Models, Animal , Electrocardiography , Female , Male , SheepABSTRACT
The ultimate solution for patients with end-stage heart failure is organ transplant. But donor hearts are limited, immunosuppression is required, and ultimately rejection can occur. Creating a functional, autologous bio-artificial heart could solve these challenges. Biofabrication of a heart comprised of scaffold and cells is one option. A natural scaffold with tissue-specific composition as well as micro- and macro-architecture can be obtained by decellularizing hearts from humans or large animals such as pigs. Decellularization involves washing out cellular debris while preserving 3D extracellular matrix and vasculature and allowing "cellularization" at a later timepoint. Capitalizing on our novel finding that perfusion decellularization of complex organs is possible, we developed a more "physiological" method to decellularize non-transplantable human hearts by placing them inside a pressurized pouch, in an inverted orientation, under controlled pressure. The purpose of using a pressurized pouch is to create pressure gradients across the aortic valve to keep it closed and improve myocardial perfusion. Simultaneous assessment of flow dynamics and cellular debris removal during decellularization allowed us to monitor both fluid inflow and debris outflow, thereby generating a scaffold that can be used either for simple cardiac repair (e.g. as a patch or valve scaffold) or as a whole-organ scaffold.
Subject(s)
Heart, Artificial , Heart/physiology , Pressure , Tissue Engineering/methods , Tissue Scaffolds , Animals , Aortic Valve/cytology , Aortic Valve/physiology , Extracellular Matrix/physiology , Heart, Artificial/standards , Humans , Perfusion , Swine , Tissue Scaffolds/standardsABSTRACT
OBJECTIVES: Currently, most of the artificial airway organs still require scaffolds; however, such scaffolds exhibit several limitations. Alternatively, the use of an autologous artificial trachea without foreign materials and immunosuppressants may solve these issues and constitute a preferred tool. The rationale of this study was to develop a new scaffold-free approach for an artificial trachea using bio-3D printing technology. Here, we assessed the circumferential tracheal replacement using scaffold-free trachea-like grafts generated from isolated cells in an inbred animal model. METHODS: Chondrocytes and mesenchymal stem cells were isolated from F344 rats. Rat lung microvessel endothelial cells were purchased. Our bio-3D printer generates spheroids consisting of several types of cells to create 3D structures. The bio-3D-printed artificial trachea from spheroids was matured in a bioreactor and transplanted into F344 rats as a tracheal graft under general anaesthesia. The mechanical strength of the artificial trachea was measured, and histological and immunohistochemical examinations were performed. RESULTS: Tracheal transplantation was performed in 9 rats, which were followed up postoperatively for 23 days. The average tensile strength of artificial tracheas before transplantation was 526.3 ± 125.7 mN. The bio-3D-printed scaffold-free artificial trachea had sufficient strength to transplant into the trachea with silicone stents that were used to prevent collapse of the artificial trachea and to support the graft until sufficient blood supply was obtained. Chondrogenesis and vasculogenesis were observed histologically. CONCLUSIONS: The scaffold-free isogenic artificial tracheas produced by a bio-3D printer could be utilized as tracheal grafts in rats.