Alice Ferng - Academia.edu (original) (raw)

Papers by Alice Ferng

Research paper thumbnail of Human Amniotic Membrane Promotes Antimicrobial Microenvironment in a Device-Related Infection

Journal of Biomedical Science and Engineering, 2016

Hospital inquired post-operative infections are a leading cause of morbidity and mortality in pat... more Hospital inquired post-operative infections are a leading cause of morbidity and mortality in patients receiving left ventricular assist devices. We present the case of a patient who acquired Candida albicans and Staphylococci infections following left ventricular assist device implantation. Use of standard antibiotics caused the infection to worsen, thus an amniotic membrane patch was used as a last-resort treatment. Within 6 weeks of the amniotic membrane patch treatment, the infection resolved, the wound appeared exceptionally clean upon inspection, and granulation tissue was present. After the infection resolved, a successful latissimusdorsi tissue flap procedure was completed and the patient made a full recovery.

Research paper thumbnail of Engineering Articular Cartilage from Human and Canine Non-Embryonic Stem Cells

Research paper thumbnail of Pre-Clinical Ex Vivo Human Recellularization of Acellular Porcine Hearts

Journal of the American College of Surgeons

Research paper thumbnail of Dehumanizing Wartime Refugees: Global Impact of Organ Trafficking

Journal of the American College of Surgeons

INTRODUCTION: In China, the prevalence of cataract is high, with some 515 million people afflicte... more INTRODUCTION: In China, the prevalence of cataract is high, with some 515 million people afflicted with the disease and varying levels of blindness. Although various philanthropic organizations have sought to alleviate the burden of disease due to cataracts, the effectiveness of interventional studies has never been investigated. This is the first study to ascertain the benefits of a lowcost train as the intervention used to train and transfer skills to local surgeons. METHODS: We analyzed 12,715 patient charts in Zhanjiang, China from 2007 to 2016. Preoperative and 3-month postoperative best-corrected visual acuity (BCVA), types and quantity of surgical procedures, intraoperative complication rates, and total costs per cataract procedure were analyzed using Bayesian Estimation Supercedes the T test (BEST) and linear regression. Cost-effectiveness was analyzed with Quality Adjusted Life Years (QALYs). RESULTS: The Lifeline Train is a highly cost-effective intervention with an average cost/QALY gained of 9,470 Chinese Yuan Renminbi in Zhanjiang. Significant changes in BCVA (p < 0.02) and number of cataract procedures (p < 0.005) were found. Significant positive correlations were seen in number of cataract procedures (R2 ¼ 0.825, p < 0.005) and number of phacoemulsifications performed (R2 ¼ 0.808, p < 0.006). There were significant negative correlations in the number of small incisions type procedures (R2 ¼ À0.701, p < 0.019). CONCLUSIONS: The Lifeline Train is the first large-scale, philanthropic intervention that successfully treats blindness and trains surgeons throughout China. The train can serve as a unique and cost-effective model to effectively and efficiently alleviate the burden of blindness, as well as to train local health workers.

Research paper thumbnail of Lung bioscaffolds: comparative lung decellularization techniques

Research paper thumbnail of Analyzing the Metabolic Microenvironment of Co‐cultured Stem Cells and Cardiomyocytes

The FASEB Journal, 2015

While there exists precedence over the last decade of decellularization of rodent, porcine, and h... more While there exists precedence over the last decade of decellularization of rodent, porcine, and human hearts to create a bioartificial heart scaffold, there remains a lot of work to be done regardi...

Research paper thumbnail of Additional file 1: of Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection

The raw data for each experimental condition used for statistical analysis is summarized in this ... more The raw data for each experimental condition used for statistical analysis is summarized in this data set. Conditions include incubation of cardiac cells in control and preservation media at 4 degrees C or 21 degrees C for 4 hours or 8 hours. Control groups were incubated in either media or phosphate-buffered saline (PBS), and treatment groups were incubated in either Celsior, Somah, or Perfadex. (XLSX 80Â kb)

Research paper thumbnail of Cardiac Organogenesis: 3D Bioscaffolds, Bioenergetics and Regeneration

Each year the Organ Procurement and Transplantation Network (OPTN) reports an increase in patient... more Each year the Organ Procurement and Transplantation Network (OPTN) reports an increase in patients requiring an organ transplant without an increase in available donor organs, leading to a transplant gap that continues to widen. Over 70% of donor hearts are deemed unsuitable for transplantation each year, and a large number of these organs (~50%) are discarded due to poor organ function, decreased ejection fraction, disease, or cardiac arrest (Scientific Registry of Transplant Recipients (SRTR) Annual Data Report 2011).We therefore set out to improve knowledge in the field of cardiac transplantation in terms of organogenesis, bioenergetics, and regeneration. The main goal through tissue bioengineering is to regenerate and salvage discarded hearts through organogenesis, or to lengthen the total organ preservation time such that organs would not be thrown away while a recipient was waiting to be found. Our first hypothesis was that an optimized acellular extracellular matrix scaffold would allow for cell adherence, growth and proliferation, and could potentially be grown into a clinically transplantable organ. To achieve these goals, an optimized protocol was developed for the total acellularization of a whole porcine heart, leaving behind a 3D bioscaffold. We showed that acellularized matrices could be successfully seeded using endothelial cells for acellular vasculature and stem cells for other acellular tissues, both as a 2D matrix and within a constantly perfused 3D Langendorff setup bioreactor. In order to best understand cell-cell and cell-matrix interactions, cellular bioenergetics were evaluated. We hypothesized that the bioenergetic demand of the type and anatomical origin of stem cells would affect the regeneration potential dependent on intrinsic metabolic demand. We therefore showed a differential of the bioenergetic profiles of human adipose-derived stem cells isolated from various adipose depots, concluding that the physiological microenvironment that supports stem cells in specific anatomic locations can regulate how stem cells participate in tissue regeneration, maintenance and repair, and also will vary based on donor-differences. During organ transplantation, organ preservation solutions are created for use at specific conditions, such as on ice or at room temperature. We hypothesized that hypothermia would slow down cellular metabolism, and that solutions containing a higher content of antioxidants and other protective substrates against ischemic reperfusion injury would create the best organ storage conditions. We tested three organ preservation solutions against control media and normal saline at 4 and 21 degrees C, for 4 to 8 hours, investigating the bioenergetics of organ preservation solution effects on cardiac cells. By simulating clinical conditions, we were able to determine that one of our solutions was ideal and had protective effects for cells for up to 8 hours at 4 degrees C. Finally, we believed that studying existing cardiac patches and optimizing cardiac matrix design would lead to improved cardiac physiological function and would aid in healing and repair during cardiac surgery. Following a clinical case report showing new cardiac tissue growth after implantation of an acellular porcine extracellular matrix, we devised a proof-of-concept study to show that clinical matrices could be easily cultured in vitro. We successfully seeded these clinical matrices using human amniotic stem cells, a commonly used cell type for regeneration and repair after surgery. Our preliminary studies suggest that preconditioned matrices can be potentially used clinically for greater efficacy and tissue regeneration.Release 01-Jul-201

Research paper thumbnail of Inducing Cartilage Regeneration with Stem Cells for Treatment of Osteoarthritis Patients

Research paper thumbnail of Additional file 1: of Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis

CARE Checklist â 2016: Information for writing a case report. (DOCX 603 kb)

Research paper thumbnail of Intraoperative thermographic imaging to assess myocardial distribution of Del Nido cardioplegia

Journal of cardiac surgery, Jan 3, 2017

We describe the intraoperative non-invasive use of an infrared (IR) camera to monitor Del Nido ca... more We describe the intraoperative non-invasive use of an infrared (IR) camera to monitor Del Nido cardioplegia delivery in patients undergoing cardiac surgery. Thermal pictures were taken pre- and post-cardioplegia and at timed points after arrest, and compared to readings from a transseptal temperature probe. There was good concordance between the transseptal probe and the IR camera temperature readings. This non-invasive technique, which assesses cardioplegic distribution, may help to determine when additional doses of Del Nido cardioplegia are required during periods of cardioplegic arrest.

Research paper thumbnail of Acellular porcine heart matrices: whole organ decellularization with 3D-Bioscaffold & vascular preservation

Journal of Clinical and Translational Research, 2017

Regenerative medicine, particularly decellularization-recellularization methods via whole-organ t... more Regenerative medicine, particularly decellularization-recellularization methods via whole-organ tissue engineering, has been increasingly studied due to the growing donor organ shortage. Though numerous decellularization protocols exist, the ideal decellularization protocol for optimal recellularization is unclear. This study was performed to optimize existing heart decellularization protocols and compare current methods using the detergents SDS (sodium dodecyl sulfate), Triton X-100, OGP (octyl β-D-glucopyranoside), and CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate) through retrograde aortic perfusion via aortic cannulation of a whole porcine heart. The goal of decellularization is to preserve extracellular matrix integrity and architecture, which was analyzed in this study through histology, microscopy, DNA analysis, hydroxyproline content analysis, materials analysis and angiography. Effective decellularization was determined by analyzing the tissue organization, geometry, and biological properties of the resultant extracellular matrix scaffold. Using these parameters, optimal decellularization was achieved between 90 and 120 mmHg pressure with 3% SDS as a detergent. Relevance for patients: This study provides important information about whole heart decellularization, which will ultimately contribute to heart bioengineering.

Research paper thumbnail of 3D printed mitral valve models: affordable simulation for robotic mitral valve repair

Interactive CardioVascular and Thoracic Surgery, 2017

OBJECTIVES 3D printed mitral valve (MV) models that capture the suture response of real tissue ma... more OBJECTIVES 3D printed mitral valve (MV) models that capture the suture response of real tissue may be utilized as surgical training tools. Leveraging clinical imaging modalities, 3D computerized modelling and 3D printing technology to produce affordable models complements currently available virtual simulators and paves the way for patient- and pathology-specific preoperative rehearsal. METHODS We used polyvinyl alcohol, a dissolvable thermoplastic, to 3D print moulds that were casted with liquid platinum-cure silicone yielding flexible, low-cost MV models capable of simulating valvular tissue. Silicone-moulded MV models were fabricated for 2 morphologies: the normal MV and the P2 flail. The moulded valves were plication and suture tested in a laparoscopic trainer box with a da Vinci Si robotic surgical system. One cardiothoracic surgery fellow and 1 attending surgeon qualitatively evaluated the ability of the valves to recapitulate tissue feel through surveys utilizing the 5-point ...

Research paper thumbnail of Cardiac Regeneration in the Human Left Ventricle After CorMatrix Implantation

The Annals of Thoracic Surgery, 2017

CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa... more CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa and is used for pericardial closure and cardiac tissue repair. During explantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) because of infection, CorMatrix was used to repair the left ventricular apex and aorta. Three months later, a HeartWare HVAD (HeartWare International, Inc, Framingham, MA) was implanted for recurrent heart failure. Excised apical CorMatrix samples showed cardiac tissue remodeling with viable cardiomyoblasts similar to native myocardium. Excised CorMatrix from the aorta showed organization of collagen and elastin similar to native aortic tissue.

Research paper thumbnail of Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis

Lung, Jan 2, 2017

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affe... more Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E2) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF -/-) were used in this study as a model for LAM. Oxygen consumption rates (OCR) and redox potential were measured to determine metabolic state across control cells, MEF +/+ and -/- cells treated with rapamycin (Rapa), and MEF +/+ and -/- cells treated with E2. An XF96 extracellular flux analyzer from Seahorse Bioscience(®) was used to measure OCR, and a RedoxSYS™ ORP was used to measure redox potential. OCR of MEF -/- cells treated with rapamycin (MEF -/- Rapa) versus MEF -/- control were significantly lower across all conditions. The static ox...

Research paper thumbnail of Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection

Journal of Cardiothoracic Surgery, 2017

Background: Heart transplantation remains the gold standard for end-stage heart failure, with cur... more Background: Heart transplantation remains the gold standard for end-stage heart failure, with current ex vivo organ storage times limited to 4 to 6 h before critical tissue damage occurs. Many preservation solutions exist in an attempt to limit both ischemic and reperfusion damage. In order to compare the effects of various storage solutions, mitochondrial function can be used to provide a sensitive analysis of cellular metabolic function. Methods: Experimental plates were seeded with cardiac myoblasts and kept in suspended animation for either 4 or 8 h at either 4 o or 21°C, in Celsior®, Perfadex®, or Somah storage solutions. Cells were then reanimated for 1 h at 37°C to simulate a reperfusion or clinical transplant scenario. Cellular bioenergetics were measured immediately thereafter to examine biochemical differences between preservation solutions and their effectiveness on preserving metabolic function. Results: The oxygen consumption rates of Somah solution were significantly higher than Celsior® and Perfadex® at 4°C, with the exception of Perfadex® at 4 o for 4 h. This effect was sustained up to 8 h. At 21°C, oxygen consumption rates of Somah solution are significantly higher than Celsior® and Perfadex® at basal conditions after 4 h, but this effect is not sustained after 8 h. Conclusions: The purpose of this experiment was to study the efficacy of various preservation solutions on a mitochondrial level. The significantly higher oxygen consumption rates of Somah at 4°C suggests that Somah solution may have the ability to protect cellular mitochondrial integrity, improve transplanted organ function by reducing ischemic-reperfusion injury, and thereby improve transplant outcomes. Given that Somah offers benefits over Celsior® and Perfadex® at 4°C, it should be a target in future organ preservation solution research.

Research paper thumbnail of Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis

Journal of cardiothoracic surgery, Jan 26, 2017

Since constrictive pericarditis is most often idiopathic and the pathophysiology remains largely ... more Since constrictive pericarditis is most often idiopathic and the pathophysiology remains largely unknown, both the diagnosis and the treatment can be challenging. However, by definition, inflammatory processes are central to this disease process. Amniotic membrane patches have been shown to possess anti-inflammatory properties and are believed to be immune privileged. Due to these properties, amniotic membrane patches were applied intraoperatively in a complicated patient presenting with constrictive pericarditis. A patient with a history of multiple cardiac surgeries presented with marked fatigue, worsening dyspnea and sinus tachycardia. He was found to have constrictive physiology during cardiac catheterization, with cardiac MRI demonstrating hepatic vein dilatation, atrial enlargement and ventricular narrowing. After amniotic membrane patch treatment and pericardiectomy, post-operative cardiac MRI failed to demonstrate any appreciable pericardial effusion or inflammation, with no...

Research paper thumbnail of Adipose-derived human stem/stromal cells: comparative organ specific mitochondrial bioenergy profiles

SpringerPlus, 2016

Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a sourc... more Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source of stem cells in particular, due to their lack of immunogenicity. This study examines differences between mitochondrial bioenergetic profiles of ASCs isolated from adipose tissue of five peri-organ regions: pericardial, thymic, knee, shoulder, and abdomen. Flow cytometry showed that the majority of each ASC population isolated from the adipose tissue of 12 donors, with an n = 3 for each tissue type, were positive for MSC markers CD90, CD73, and CD105, and negative for hematopoietic markers CD34, CD11B, CD19, and CD45. Bioenergetic profiles were obtained for ASCs with an n = 4 for each tissue type and graphed together for comparison. Mitochondrial stress tests provided the following measurements: basal respiration rate (measured as oxygen consumption ...

Research paper thumbnail of Translation of First North American 50 and 70 cc Total Artificial Heart Virtual and Clinical Implantations: Utility of 3D Computed Tomography to Test Fit Devices

Artificial Organs, 2016

Since the creation of SynCardia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Since the creation of SynCardia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 50 cc Total Artificial Hearts (TAHs), patients with irreversible biventricular failure now have two sizing options. Herein, a case series of three patients who have undergone successful 50 and 70 cc TAH implantation with complete closure of the chest cavity utilizing preoperative &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;virtual implantation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; of different sized devices for surgical planning are presented. Computed tomography (CT) images were used for preoperative planning prior to TAH implantation. Three-dimensional (3D) reconstructions of preoperative chest CT images were generated and both 50 and 70 cc TAHs were virtually implanted into patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; thoracic cavities. During the simulation, the TAHs were projected over the native hearts in a similar position to the actual implantation, and the relationship between the devices and the atria, ventricles, chest wall, and diaphragm were assessed. The 3D reconstructed images and virtual modeling were used to simulate and determine for each patient if the 50 or 70 cc TAH would have a higher likelihood of successful implantation without complications. Subsequently, all three patients received clinical implants of the properly sized TAH based on virtual modeling, and their chest cavities were fully closed. This virtual implantation increases our confidence that the selected TAH will better fit within the thoracic cavity allowing for improved surgical outcome. Clinical implantation of the TAHs showed that our virtual modeling was an effective method for determining the correct fit and sizing of 50 and 70 cc TAHs.

Research paper thumbnail of The Role of MHealth and Wearables for Anticipation in Medicine

Anticipation and Medicine, 2016

As the market for health-tracking wearable devices continues to expand, there is an emerging nich... more As the market for health-tracking wearable devices continues to expand, there is an emerging niche for healthcare applications, and data acquisition and usage. Within this area exists a wealth of clinically relevant data already collected from wearers, including physiological and lifestyle data. This information allows us to not only optimize current medical treatments and health planning, but also to expand preventive medicine by applying anticipation to medicine. We propose that much of the data collected through these wearable devices can be used to inform both patient and clinician of long-term physiological trends, and to anticipate potential onset of illnesses with a view to stemming their progression, or even mitigating their occurrence altogether. This paper highlights important issues within the health-wearable paradigm and presents upcoming applications of wearable technologies in medicine.

Research paper thumbnail of Human Amniotic Membrane Promotes Antimicrobial Microenvironment in a Device-Related Infection

Journal of Biomedical Science and Engineering, 2016

Hospital inquired post-operative infections are a leading cause of morbidity and mortality in pat... more Hospital inquired post-operative infections are a leading cause of morbidity and mortality in patients receiving left ventricular assist devices. We present the case of a patient who acquired Candida albicans and Staphylococci infections following left ventricular assist device implantation. Use of standard antibiotics caused the infection to worsen, thus an amniotic membrane patch was used as a last-resort treatment. Within 6 weeks of the amniotic membrane patch treatment, the infection resolved, the wound appeared exceptionally clean upon inspection, and granulation tissue was present. After the infection resolved, a successful latissimusdorsi tissue flap procedure was completed and the patient made a full recovery.

Research paper thumbnail of Engineering Articular Cartilage from Human and Canine Non-Embryonic Stem Cells

Research paper thumbnail of Pre-Clinical Ex Vivo Human Recellularization of Acellular Porcine Hearts

Journal of the American College of Surgeons

Research paper thumbnail of Dehumanizing Wartime Refugees: Global Impact of Organ Trafficking

Journal of the American College of Surgeons

INTRODUCTION: In China, the prevalence of cataract is high, with some 515 million people afflicte... more INTRODUCTION: In China, the prevalence of cataract is high, with some 515 million people afflicted with the disease and varying levels of blindness. Although various philanthropic organizations have sought to alleviate the burden of disease due to cataracts, the effectiveness of interventional studies has never been investigated. This is the first study to ascertain the benefits of a lowcost train as the intervention used to train and transfer skills to local surgeons. METHODS: We analyzed 12,715 patient charts in Zhanjiang, China from 2007 to 2016. Preoperative and 3-month postoperative best-corrected visual acuity (BCVA), types and quantity of surgical procedures, intraoperative complication rates, and total costs per cataract procedure were analyzed using Bayesian Estimation Supercedes the T test (BEST) and linear regression. Cost-effectiveness was analyzed with Quality Adjusted Life Years (QALYs). RESULTS: The Lifeline Train is a highly cost-effective intervention with an average cost/QALY gained of 9,470 Chinese Yuan Renminbi in Zhanjiang. Significant changes in BCVA (p < 0.02) and number of cataract procedures (p < 0.005) were found. Significant positive correlations were seen in number of cataract procedures (R2 ¼ 0.825, p < 0.005) and number of phacoemulsifications performed (R2 ¼ 0.808, p < 0.006). There were significant negative correlations in the number of small incisions type procedures (R2 ¼ À0.701, p < 0.019). CONCLUSIONS: The Lifeline Train is the first large-scale, philanthropic intervention that successfully treats blindness and trains surgeons throughout China. The train can serve as a unique and cost-effective model to effectively and efficiently alleviate the burden of blindness, as well as to train local health workers.

Research paper thumbnail of Lung bioscaffolds: comparative lung decellularization techniques

Research paper thumbnail of Analyzing the Metabolic Microenvironment of Co‐cultured Stem Cells and Cardiomyocytes

The FASEB Journal, 2015

While there exists precedence over the last decade of decellularization of rodent, porcine, and h... more While there exists precedence over the last decade of decellularization of rodent, porcine, and human hearts to create a bioartificial heart scaffold, there remains a lot of work to be done regardi...

Research paper thumbnail of Additional file 1: of Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection

The raw data for each experimental condition used for statistical analysis is summarized in this ... more The raw data for each experimental condition used for statistical analysis is summarized in this data set. Conditions include incubation of cardiac cells in control and preservation media at 4 degrees C or 21 degrees C for 4 hours or 8 hours. Control groups were incubated in either media or phosphate-buffered saline (PBS), and treatment groups were incubated in either Celsior, Somah, or Perfadex. (XLSX 80Â kb)

Research paper thumbnail of Cardiac Organogenesis: 3D Bioscaffolds, Bioenergetics and Regeneration

Each year the Organ Procurement and Transplantation Network (OPTN) reports an increase in patient... more Each year the Organ Procurement and Transplantation Network (OPTN) reports an increase in patients requiring an organ transplant without an increase in available donor organs, leading to a transplant gap that continues to widen. Over 70% of donor hearts are deemed unsuitable for transplantation each year, and a large number of these organs (~50%) are discarded due to poor organ function, decreased ejection fraction, disease, or cardiac arrest (Scientific Registry of Transplant Recipients (SRTR) Annual Data Report 2011).We therefore set out to improve knowledge in the field of cardiac transplantation in terms of organogenesis, bioenergetics, and regeneration. The main goal through tissue bioengineering is to regenerate and salvage discarded hearts through organogenesis, or to lengthen the total organ preservation time such that organs would not be thrown away while a recipient was waiting to be found. Our first hypothesis was that an optimized acellular extracellular matrix scaffold would allow for cell adherence, growth and proliferation, and could potentially be grown into a clinically transplantable organ. To achieve these goals, an optimized protocol was developed for the total acellularization of a whole porcine heart, leaving behind a 3D bioscaffold. We showed that acellularized matrices could be successfully seeded using endothelial cells for acellular vasculature and stem cells for other acellular tissues, both as a 2D matrix and within a constantly perfused 3D Langendorff setup bioreactor. In order to best understand cell-cell and cell-matrix interactions, cellular bioenergetics were evaluated. We hypothesized that the bioenergetic demand of the type and anatomical origin of stem cells would affect the regeneration potential dependent on intrinsic metabolic demand. We therefore showed a differential of the bioenergetic profiles of human adipose-derived stem cells isolated from various adipose depots, concluding that the physiological microenvironment that supports stem cells in specific anatomic locations can regulate how stem cells participate in tissue regeneration, maintenance and repair, and also will vary based on donor-differences. During organ transplantation, organ preservation solutions are created for use at specific conditions, such as on ice or at room temperature. We hypothesized that hypothermia would slow down cellular metabolism, and that solutions containing a higher content of antioxidants and other protective substrates against ischemic reperfusion injury would create the best organ storage conditions. We tested three organ preservation solutions against control media and normal saline at 4 and 21 degrees C, for 4 to 8 hours, investigating the bioenergetics of organ preservation solution effects on cardiac cells. By simulating clinical conditions, we were able to determine that one of our solutions was ideal and had protective effects for cells for up to 8 hours at 4 degrees C. Finally, we believed that studying existing cardiac patches and optimizing cardiac matrix design would lead to improved cardiac physiological function and would aid in healing and repair during cardiac surgery. Following a clinical case report showing new cardiac tissue growth after implantation of an acellular porcine extracellular matrix, we devised a proof-of-concept study to show that clinical matrices could be easily cultured in vitro. We successfully seeded these clinical matrices using human amniotic stem cells, a commonly used cell type for regeneration and repair after surgery. Our preliminary studies suggest that preconditioned matrices can be potentially used clinically for greater efficacy and tissue regeneration.Release 01-Jul-201

Research paper thumbnail of Inducing Cartilage Regeneration with Stem Cells for Treatment of Osteoarthritis Patients

Research paper thumbnail of Additional file 1: of Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis

CARE Checklist â 2016: Information for writing a case report. (DOCX 603 kb)

Research paper thumbnail of Intraoperative thermographic imaging to assess myocardial distribution of Del Nido cardioplegia

Journal of cardiac surgery, Jan 3, 2017

We describe the intraoperative non-invasive use of an infrared (IR) camera to monitor Del Nido ca... more We describe the intraoperative non-invasive use of an infrared (IR) camera to monitor Del Nido cardioplegia delivery in patients undergoing cardiac surgery. Thermal pictures were taken pre- and post-cardioplegia and at timed points after arrest, and compared to readings from a transseptal temperature probe. There was good concordance between the transseptal probe and the IR camera temperature readings. This non-invasive technique, which assesses cardioplegic distribution, may help to determine when additional doses of Del Nido cardioplegia are required during periods of cardioplegic arrest.

Research paper thumbnail of Acellular porcine heart matrices: whole organ decellularization with 3D-Bioscaffold & vascular preservation

Journal of Clinical and Translational Research, 2017

Regenerative medicine, particularly decellularization-recellularization methods via whole-organ t... more Regenerative medicine, particularly decellularization-recellularization methods via whole-organ tissue engineering, has been increasingly studied due to the growing donor organ shortage. Though numerous decellularization protocols exist, the ideal decellularization protocol for optimal recellularization is unclear. This study was performed to optimize existing heart decellularization protocols and compare current methods using the detergents SDS (sodium dodecyl sulfate), Triton X-100, OGP (octyl β-D-glucopyranoside), and CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate) through retrograde aortic perfusion via aortic cannulation of a whole porcine heart. The goal of decellularization is to preserve extracellular matrix integrity and architecture, which was analyzed in this study through histology, microscopy, DNA analysis, hydroxyproline content analysis, materials analysis and angiography. Effective decellularization was determined by analyzing the tissue organization, geometry, and biological properties of the resultant extracellular matrix scaffold. Using these parameters, optimal decellularization was achieved between 90 and 120 mmHg pressure with 3% SDS as a detergent. Relevance for patients: This study provides important information about whole heart decellularization, which will ultimately contribute to heart bioengineering.

Research paper thumbnail of 3D printed mitral valve models: affordable simulation for robotic mitral valve repair

Interactive CardioVascular and Thoracic Surgery, 2017

OBJECTIVES 3D printed mitral valve (MV) models that capture the suture response of real tissue ma... more OBJECTIVES 3D printed mitral valve (MV) models that capture the suture response of real tissue may be utilized as surgical training tools. Leveraging clinical imaging modalities, 3D computerized modelling and 3D printing technology to produce affordable models complements currently available virtual simulators and paves the way for patient- and pathology-specific preoperative rehearsal. METHODS We used polyvinyl alcohol, a dissolvable thermoplastic, to 3D print moulds that were casted with liquid platinum-cure silicone yielding flexible, low-cost MV models capable of simulating valvular tissue. Silicone-moulded MV models were fabricated for 2 morphologies: the normal MV and the P2 flail. The moulded valves were plication and suture tested in a laparoscopic trainer box with a da Vinci Si robotic surgical system. One cardiothoracic surgery fellow and 1 attending surgeon qualitatively evaluated the ability of the valves to recapitulate tissue feel through surveys utilizing the 5-point ...

Research paper thumbnail of Cardiac Regeneration in the Human Left Ventricle After CorMatrix Implantation

The Annals of Thoracic Surgery, 2017

CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa... more CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa and is used for pericardial closure and cardiac tissue repair. During explantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) because of infection, CorMatrix was used to repair the left ventricular apex and aorta. Three months later, a HeartWare HVAD (HeartWare International, Inc, Framingham, MA) was implanted for recurrent heart failure. Excised apical CorMatrix samples showed cardiac tissue remodeling with viable cardiomyoblasts similar to native myocardium. Excised CorMatrix from the aorta showed organization of collagen and elastin similar to native aortic tissue.

Research paper thumbnail of Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis

Lung, Jan 2, 2017

Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affe... more Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E2) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF -/-) were used in this study as a model for LAM. Oxygen consumption rates (OCR) and redox potential were measured to determine metabolic state across control cells, MEF +/+ and -/- cells treated with rapamycin (Rapa), and MEF +/+ and -/- cells treated with E2. An XF96 extracellular flux analyzer from Seahorse Bioscience(®) was used to measure OCR, and a RedoxSYS™ ORP was used to measure redox potential. OCR of MEF -/- cells treated with rapamycin (MEF -/- Rapa) versus MEF -/- control were significantly lower across all conditions. The static ox...

Research paper thumbnail of Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection

Journal of Cardiothoracic Surgery, 2017

Background: Heart transplantation remains the gold standard for end-stage heart failure, with cur... more Background: Heart transplantation remains the gold standard for end-stage heart failure, with current ex vivo organ storage times limited to 4 to 6 h before critical tissue damage occurs. Many preservation solutions exist in an attempt to limit both ischemic and reperfusion damage. In order to compare the effects of various storage solutions, mitochondrial function can be used to provide a sensitive analysis of cellular metabolic function. Methods: Experimental plates were seeded with cardiac myoblasts and kept in suspended animation for either 4 or 8 h at either 4 o or 21°C, in Celsior®, Perfadex®, or Somah storage solutions. Cells were then reanimated for 1 h at 37°C to simulate a reperfusion or clinical transplant scenario. Cellular bioenergetics were measured immediately thereafter to examine biochemical differences between preservation solutions and their effectiveness on preserving metabolic function. Results: The oxygen consumption rates of Somah solution were significantly higher than Celsior® and Perfadex® at 4°C, with the exception of Perfadex® at 4 o for 4 h. This effect was sustained up to 8 h. At 21°C, oxygen consumption rates of Somah solution are significantly higher than Celsior® and Perfadex® at basal conditions after 4 h, but this effect is not sustained after 8 h. Conclusions: The purpose of this experiment was to study the efficacy of various preservation solutions on a mitochondrial level. The significantly higher oxygen consumption rates of Somah at 4°C suggests that Somah solution may have the ability to protect cellular mitochondrial integrity, improve transplanted organ function by reducing ischemic-reperfusion injury, and thereby improve transplant outcomes. Given that Somah offers benefits over Celsior® and Perfadex® at 4°C, it should be a target in future organ preservation solution research.

Research paper thumbnail of Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis

Journal of cardiothoracic surgery, Jan 26, 2017

Since constrictive pericarditis is most often idiopathic and the pathophysiology remains largely ... more Since constrictive pericarditis is most often idiopathic and the pathophysiology remains largely unknown, both the diagnosis and the treatment can be challenging. However, by definition, inflammatory processes are central to this disease process. Amniotic membrane patches have been shown to possess anti-inflammatory properties and are believed to be immune privileged. Due to these properties, amniotic membrane patches were applied intraoperatively in a complicated patient presenting with constrictive pericarditis. A patient with a history of multiple cardiac surgeries presented with marked fatigue, worsening dyspnea and sinus tachycardia. He was found to have constrictive physiology during cardiac catheterization, with cardiac MRI demonstrating hepatic vein dilatation, atrial enlargement and ventricular narrowing. After amniotic membrane patch treatment and pericardiectomy, post-operative cardiac MRI failed to demonstrate any appreciable pericardial effusion or inflammation, with no...

Research paper thumbnail of Adipose-derived human stem/stromal cells: comparative organ specific mitochondrial bioenergy profiles

SpringerPlus, 2016

Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a sourc... more Adipose-derived stem/stromal cells (ASCs) isolated from the stromal vascular fraction are a source of mesenchymal stem cells that have been shown to be beneficial in many regenerative medicine applications. ASCs are an attractive source of stem cells in particular, due to their lack of immunogenicity. This study examines differences between mitochondrial bioenergetic profiles of ASCs isolated from adipose tissue of five peri-organ regions: pericardial, thymic, knee, shoulder, and abdomen. Flow cytometry showed that the majority of each ASC population isolated from the adipose tissue of 12 donors, with an n = 3 for each tissue type, were positive for MSC markers CD90, CD73, and CD105, and negative for hematopoietic markers CD34, CD11B, CD19, and CD45. Bioenergetic profiles were obtained for ASCs with an n = 4 for each tissue type and graphed together for comparison. Mitochondrial stress tests provided the following measurements: basal respiration rate (measured as oxygen consumption ...

Research paper thumbnail of Translation of First North American 50 and 70 cc Total Artificial Heart Virtual and Clinical Implantations: Utility of 3D Computed Tomography to Test Fit Devices

Artificial Organs, 2016

Since the creation of SynCardia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more Since the creation of SynCardia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 50 cc Total Artificial Hearts (TAHs), patients with irreversible biventricular failure now have two sizing options. Herein, a case series of three patients who have undergone successful 50 and 70 cc TAH implantation with complete closure of the chest cavity utilizing preoperative &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;virtual implantation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; of different sized devices for surgical planning are presented. Computed tomography (CT) images were used for preoperative planning prior to TAH implantation. Three-dimensional (3D) reconstructions of preoperative chest CT images were generated and both 50 and 70 cc TAHs were virtually implanted into patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; thoracic cavities. During the simulation, the TAHs were projected over the native hearts in a similar position to the actual implantation, and the relationship between the devices and the atria, ventricles, chest wall, and diaphragm were assessed. The 3D reconstructed images and virtual modeling were used to simulate and determine for each patient if the 50 or 70 cc TAH would have a higher likelihood of successful implantation without complications. Subsequently, all three patients received clinical implants of the properly sized TAH based on virtual modeling, and their chest cavities were fully closed. This virtual implantation increases our confidence that the selected TAH will better fit within the thoracic cavity allowing for improved surgical outcome. Clinical implantation of the TAHs showed that our virtual modeling was an effective method for determining the correct fit and sizing of 50 and 70 cc TAHs.

Research paper thumbnail of The Role of MHealth and Wearables for Anticipation in Medicine

Anticipation and Medicine, 2016

As the market for health-tracking wearable devices continues to expand, there is an emerging nich... more As the market for health-tracking wearable devices continues to expand, there is an emerging niche for healthcare applications, and data acquisition and usage. Within this area exists a wealth of clinically relevant data already collected from wearers, including physiological and lifestyle data. This information allows us to not only optimize current medical treatments and health planning, but also to expand preventive medicine by applying anticipation to medicine. We propose that much of the data collected through these wearable devices can be used to inform both patient and clinician of long-term physiological trends, and to anticipate potential onset of illnesses with a view to stemming their progression, or even mitigating their occurrence altogether. This paper highlights important issues within the health-wearable paradigm and presents upcoming applications of wearable technologies in medicine.