Justin Farry | Stanford University (original) (raw)
Papers by Justin Farry
Circulation
Objective: The incidence of post-operative adhesions is estimated to be 93%, resulting in severe ... more Objective: The incidence of post-operative adhesions is estimated to be 93%, resulting in severe pain, bowel obstruction, infertility, and often requires re-operation. Mainstay adhesion prevention technologies are generally derived from polymer films that serve as physical barriers between scarring tissue and surrounding organs. Yet, these films have not been widely accepted due to their inability to adequately limit adhesions and difficulty handling during surgery. We hypothesized shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would instead provide a novel, viscoelastic barrier between tissues and organs, allowing tissues to move past each other similar to the body’s natural state, effectively preventing adhesion formation (Fig. 1A). Methods: PNP shear-thinning and self-healing behavior was characterized via rheometry. Adult male Sprague Dawley rats (n=23) underwent sham surgery or permanent ligation of the LAD followed by pericardial application of 250μL PNP gel...
Supplemental Material from "Biomimetic Six-Axis Robots Replicate Human Cardiac Papillary Mus... more Supplemental Material from "Biomimetic Six-Axis Robots Replicate Human Cardiac Papillary Muscle Motion: Pioneering the Next Generation of Biomechanical Heart Simulator Technology"
Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitr... more Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In <i>ex vivo</i> heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularit...
Movie of the dual IPM robots simulating native papillary muscle motion during an ex vivo cardiac ... more Movie of the dual IPM robots simulating native papillary muscle motion during an ex vivo cardiac simulation experiment. The movement was dictated by high-resolution CT scans of a healthy human heart. This motion is compared to previous ex vivo experimentation with the papillary muscles held stationary.
Circulation
Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and c... more Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A). Methods: Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm 2 ), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm 2 ), or no treatment. Degree of adhesion formation, standardized disse...
Circulation
Introduction: Very few technologies exist that can provide quantitative data on forces within the... more Introduction: Very few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker based strain measurements can be performed, but chordae heterogeneity limits utility. Foil-based strain sensors have also been described, but tend to be bulky, limiting the number of chordae that can be measured. Hypothesis: We hypothesize that the use of Fiber Bragg Grating (FBG) sensors—optical strain gauges made of 125 μ m diameter silica fibers— can overcome the critical limitations of previous methods of measuring chordae tendineae forces. Methods: Using FBG sensors, we created a force-sensing neochord that would mimic the natural shape and movement of native chordae tendineae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings - when a force is applied, the gratings move relative to one another, changing the reflected light (Fig 1A). This wavelength shift is directly proportional to the force applied. The F...
Journal of the Mechanical Behavior of Biomedical Materials
Circulation
Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, s... more Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, single-suture technique for correcting posterior leaflet prolapse. While this technique has demonstrated clinical efficacy, a possible limitation is the stability of the suture anchored into myocardium as opposed to the fibrous portion of a papillary muscle. Hypothesis: We hypothesize that the PVAN suture serves only to position the leaflet for coaptation, after which systolic forces will be distributed throughout the valve, resulting in low peak forces on the suture. Methods: A left heart simulator was constructed using 3D printing, tuned to generate physiological pressure and flow waveforms, then validated. Porcine mitral valves (n=9) were dissected and mounted within the simulator. Chordal forces were measured using Fiber Bragg Grating (FBG) sensors, sewn in place using PTFE suture. FBG sensors are strain gauges made of 125 μ m optical fibers that use reflected peak wavelength changes ...
Circulation, 2018
Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) resu... more Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Methods: Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=2...
2016 IEEE International Ultrasonics Symposium (IUS), 2016
Long circulation lifetime, large therapeutic payload, and inherent biocompatibility make engineer... more Long circulation lifetime, large therapeutic payload, and inherent biocompatibility make engineered red blood cells (RBC) an attractive therapeutic delivery agent. However, drug release from conventional RBC carriers is diffusion limited and cannot be spatiotemporally controlled, thereby precluding targeted delivery to specific tissues. We have developed modified RBC carriers intended to function as image-guided therapeutic delivery agents. These new RBC carriers contain acoustically activatable perfluorocarbon droplets to enable ultrasound-mediated drug release, are loaded with iron oxide nanoparticles to permit magnetic targeting, and contain indocyanine green (ICG) dye to allow photoacoustic (PA) tracking of RBC accumulation. In this work, we evaluate the feasibility of detecting ICG-loaded RBCs against a whole blood background via spectroscopic PA imaging. We also characterize the increase in PA signal resultant from magnetic targeting of ICG-loaded RBCs.
Circulation, 2017
Objective: Cell-sheet derived vessels have been successfully tested as bypass grafts with proven ... more Objective: Cell-sheet derived vessels have been successfully tested as bypass grafts with proven patency and vasoreactivity in both animal models and patients. However, their construction is time c...
Objective: Shear-thinning hydrogels are promising vehicles for minimally invasive drug delivery. ... more Objective: Shear-thinning hydrogels are promising vehicles for minimally invasive drug delivery. Continued development of advanced hydrogels is necessary to maximize their therapeutic potential. In this study, we encapsulated an engineered angiogenic cytokine, stromal cell-derived factor 1-α (ESA) in a novel, injectable hydrogel which undergoes a dual crosslinking mechanism. The first crosslinking step occurs ex situ via dynamic covalent bonds. The second step occurs in situ via thermal phase transition at body temperature to enforce the network, extending ESA release. We hypothesized that delivery of ESA via this novel, bioengineered hydrogel would facilitate targeted, sustained intramyocardial release, thereby prolonging endothelial progenitor cell (EPC) homing and improving left ventricular (LV) function in a rat model of myocardial ischemia. Methods: Cytoprotective and migratory effects of ESA on human EPCs were assessed via WST1 viability and QCM chemotaxis assays. Hydrogel rel...
Circulation
Introduction: Synechococcus elongatus is a cyanobacterium that grows photoautotrophically. We hyp... more Introduction: Synechococcus elongatus is a cyanobacterium that grows photoautotrophically. We hypothesized that a biologic gel containing S. elongatus could provide O 2 via photosynthesis to ischemic tissue due to peripheral arterial disease to accelerate wound healing. Methods: Sodium hyaluronate powder was mixed with cyanobacterial growth media BG11 at 2wt% to create the gel. S. elongatus was added at 100 million cells/mL to create the biologic gel. Wistar rats (control, n=12; gel, n=10; biologic gel in light, n=13; biologic gel in dark, n=10), after femoral artery ligation, received an ipsilateral wound of 1cm in diameter on the tarsal surface using electrocautery. Wound dressings were changed daily. Lesions were harvested on day 7 for histology evaluation, and blood samples were collected. Results: Rat tarsal tissue O 2 level had the largest fold change after applying biologic gel in light (7.0±1.5) compared to the control (1.7±0.3, p =.004), gel (2.6±0.4, p =.0007), and biologi...
Circulation
Background: Many graft configurations are clinically used for valve-sparing aortic root replaceme... more Background: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. Methods: Using a custom 3-dimenstional–printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey’s correction. Results: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between g...
Journal of The Royal Society Interface
Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitr... more Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a...
Journal of Cardiovascular Translational Research
Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mi... more Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract
The Journal of Thoracic and Cardiovascular Surgery
OBJECTIVE The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid ... more OBJECTIVE The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation. METHODS Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair. RESULTS The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively. CONCLUSIONS An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.
Tissue Engineering Part A
Cell sheet technology using UpCell™ plates is a modern tool that enables the rapid creation of a ... more Cell sheet technology using UpCell™ plates is a modern tool that enables the rapid creation of a single-layered cells without using extracellular matrix enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant extracellular matrix component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 hours on UpCell™ plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50µg/mL and 100µg/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6±1.0, 14.4±6.6, and 19.8±3.8 kPa during the loading condition, and 10.3±4.7, 11.7±2.2, and 18.1±3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.
Circulation
Objective: The incidence of post-operative adhesions is estimated to be 93%, resulting in severe ... more Objective: The incidence of post-operative adhesions is estimated to be 93%, resulting in severe pain, bowel obstruction, infertility, and often requires re-operation. Mainstay adhesion prevention technologies are generally derived from polymer films that serve as physical barriers between scarring tissue and surrounding organs. Yet, these films have not been widely accepted due to their inability to adequately limit adhesions and difficulty handling during surgery. We hypothesized shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would instead provide a novel, viscoelastic barrier between tissues and organs, allowing tissues to move past each other similar to the body’s natural state, effectively preventing adhesion formation (Fig. 1A). Methods: PNP shear-thinning and self-healing behavior was characterized via rheometry. Adult male Sprague Dawley rats (n=23) underwent sham surgery or permanent ligation of the LAD followed by pericardial application of 250μL PNP gel...
Supplemental Material from "Biomimetic Six-Axis Robots Replicate Human Cardiac Papillary Mus... more Supplemental Material from "Biomimetic Six-Axis Robots Replicate Human Cardiac Papillary Muscle Motion: Pioneering the Next Generation of Biomechanical Heart Simulator Technology"
Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitr... more Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In <i>ex vivo</i> heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularit...
Movie of the dual IPM robots simulating native papillary muscle motion during an ex vivo cardiac ... more Movie of the dual IPM robots simulating native papillary muscle motion during an ex vivo cardiac simulation experiment. The movement was dictated by high-resolution CT scans of a healthy human heart. This motion is compared to previous ex vivo experimentation with the papillary muscles held stationary.
Circulation
Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and c... more Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A). Methods: Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm 2 ), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm 2 ), or no treatment. Degree of adhesion formation, standardized disse...
Circulation
Introduction: Very few technologies exist that can provide quantitative data on forces within the... more Introduction: Very few technologies exist that can provide quantitative data on forces within the mitral valve apparatus. Marker based strain measurements can be performed, but chordae heterogeneity limits utility. Foil-based strain sensors have also been described, but tend to be bulky, limiting the number of chordae that can be measured. Hypothesis: We hypothesize that the use of Fiber Bragg Grating (FBG) sensors—optical strain gauges made of 125 μ m diameter silica fibers— can overcome the critical limitations of previous methods of measuring chordae tendineae forces. Methods: Using FBG sensors, we created a force-sensing neochord that would mimic the natural shape and movement of native chordae tendineae. FBG sensors reflect a specific wavelength of light depending on the spatial period of gratings - when a force is applied, the gratings move relative to one another, changing the reflected light (Fig 1A). This wavelength shift is directly proportional to the force applied. The F...
Journal of the Mechanical Behavior of Biomedical Materials
Circulation
Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, s... more Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, single-suture technique for correcting posterior leaflet prolapse. While this technique has demonstrated clinical efficacy, a possible limitation is the stability of the suture anchored into myocardium as opposed to the fibrous portion of a papillary muscle. Hypothesis: We hypothesize that the PVAN suture serves only to position the leaflet for coaptation, after which systolic forces will be distributed throughout the valve, resulting in low peak forces on the suture. Methods: A left heart simulator was constructed using 3D printing, tuned to generate physiological pressure and flow waveforms, then validated. Porcine mitral valves (n=9) were dissected and mounted within the simulator. Chordal forces were measured using Fiber Bragg Grating (FBG) sensors, sewn in place using PTFE suture. FBG sensors are strain gauges made of 125 μ m optical fibers that use reflected peak wavelength changes ...
Circulation, 2018
Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) resu... more Introduction: Adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) results in abnormal tissue biomechanics and impaired cardiac function, ultimately leading to heart failure. We hypothesized that intramyocardial delivery of engineered stromal cell-derived factor 1α analog (ESA), our previously-developed supra-efficient pro-angiogenic chemokine, preserves biaxial LV mechanical properties after MI. Methods: Male Wistar rats (n=46) underwent sham surgery (n=15) or permanent left anterior descending coronary artery ligation (n=31). Rats sustaining MI were randomized for intramyocardial injections of either saline (100 μL, n=15) or ESA (6 μg/kg, n=16), delivered at standardized peri-infarct sites. After 4 weeks, echocardiography was performed, and the hearts were explanted. Biaxial tensile testing of the anterior LV wall was performed using a strain-controlled biaxial load frame (Fig. 1A), producing up to physiologic circumferential and longitudinal strains (ε=2...
2016 IEEE International Ultrasonics Symposium (IUS), 2016
Long circulation lifetime, large therapeutic payload, and inherent biocompatibility make engineer... more Long circulation lifetime, large therapeutic payload, and inherent biocompatibility make engineered red blood cells (RBC) an attractive therapeutic delivery agent. However, drug release from conventional RBC carriers is diffusion limited and cannot be spatiotemporally controlled, thereby precluding targeted delivery to specific tissues. We have developed modified RBC carriers intended to function as image-guided therapeutic delivery agents. These new RBC carriers contain acoustically activatable perfluorocarbon droplets to enable ultrasound-mediated drug release, are loaded with iron oxide nanoparticles to permit magnetic targeting, and contain indocyanine green (ICG) dye to allow photoacoustic (PA) tracking of RBC accumulation. In this work, we evaluate the feasibility of detecting ICG-loaded RBCs against a whole blood background via spectroscopic PA imaging. We also characterize the increase in PA signal resultant from magnetic targeting of ICG-loaded RBCs.
Circulation, 2017
Objective: Cell-sheet derived vessels have been successfully tested as bypass grafts with proven ... more Objective: Cell-sheet derived vessels have been successfully tested as bypass grafts with proven patency and vasoreactivity in both animal models and patients. However, their construction is time c...
Objective: Shear-thinning hydrogels are promising vehicles for minimally invasive drug delivery. ... more Objective: Shear-thinning hydrogels are promising vehicles for minimally invasive drug delivery. Continued development of advanced hydrogels is necessary to maximize their therapeutic potential. In this study, we encapsulated an engineered angiogenic cytokine, stromal cell-derived factor 1-α (ESA) in a novel, injectable hydrogel which undergoes a dual crosslinking mechanism. The first crosslinking step occurs ex situ via dynamic covalent bonds. The second step occurs in situ via thermal phase transition at body temperature to enforce the network, extending ESA release. We hypothesized that delivery of ESA via this novel, bioengineered hydrogel would facilitate targeted, sustained intramyocardial release, thereby prolonging endothelial progenitor cell (EPC) homing and improving left ventricular (LV) function in a rat model of myocardial ischemia. Methods: Cytoprotective and migratory effects of ESA on human EPCs were assessed via WST1 viability and QCM chemotaxis assays. Hydrogel rel...
Circulation
Introduction: Synechococcus elongatus is a cyanobacterium that grows photoautotrophically. We hyp... more Introduction: Synechococcus elongatus is a cyanobacterium that grows photoautotrophically. We hypothesized that a biologic gel containing S. elongatus could provide O 2 via photosynthesis to ischemic tissue due to peripheral arterial disease to accelerate wound healing. Methods: Sodium hyaluronate powder was mixed with cyanobacterial growth media BG11 at 2wt% to create the gel. S. elongatus was added at 100 million cells/mL to create the biologic gel. Wistar rats (control, n=12; gel, n=10; biologic gel in light, n=13; biologic gel in dark, n=10), after femoral artery ligation, received an ipsilateral wound of 1cm in diameter on the tarsal surface using electrocautery. Wound dressings were changed daily. Lesions were harvested on day 7 for histology evaluation, and blood samples were collected. Results: Rat tarsal tissue O 2 level had the largest fold change after applying biologic gel in light (7.0±1.5) compared to the control (1.7±0.3, p =.004), gel (2.6±0.4, p =.0007), and biologi...
Circulation
Background: Many graft configurations are clinically used for valve-sparing aortic root replaceme... more Background: Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown. Methods: Using a custom 3-dimenstional–printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey’s correction. Results: Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between g...
Journal of The Royal Society Interface
Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitr... more Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a...
Journal of Cardiovascular Translational Research
Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mi... more Although ex vivo simulation is a valuable tool for surgical optimization, a disease model that mimics human aortic regurgitation (AR) from cusp prolapse is needed to accurately examine valve biomechanics. To simulate AR, four porcine aortic valves were explanted, and the commissure between the two largest leaflets was detached and re-implanted 5 mm lower to induce cusp prolapse. Four additional valves were tested in their native state as controls. All valves were tested in a heart simulator while hemodynamics, high-speed videography, and echocardiography data were collected. Our AR model successfully reproduced cusp prolapse with significant increase in regurgitant volume compared with that of the controls (23.2 ± 8.9 versus 2.8 ± 1.6 ml, p = 0.017). Hemodynamics data confirmed the simulation of physiologic disease conditions. Echocardiography and color flow mapping demonstrated the presence of mild to moderate eccentric regurgitation in our AR model. This novel AR model has enormous potential in the evaluation of valve biomechanics and surgical repair techniques. Graphical Abstract
The Journal of Thoracic and Cardiovascular Surgery
OBJECTIVE The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid ... more OBJECTIVE The objective was to design and evaluate a clinically relevant, novel ex vivo bicuspid aortic valve model that mimics the most common human phenotype with associated aortic regurgitation. METHODS Three bovine aortic valves were mounted asymmetrically in a previously validated 3-dimensional-printed left heart simulator. The non-right commissure and the non-left commissure were both shifted slightly toward the left-right commissure, and the left and right coronary cusps were sewn together. The left-right commissure was then detached and reimplanted 10 mm lower than its native height. Free margin shortening was used for valve repair. Hemodynamic status, high-speed videography, and echocardiography data were collected before and after the repair. RESULTS The bicuspid aortic valve model was successfully produced and repaired. High-speed videography confirmed prolapse of the fused cusp of the baseline bicuspid aortic valve models in diastole. Hemodynamic and pressure data confirmed accurate simulation of diseased conditions with aortic regurgitation and the subsequent repair. Regurgitant fraction postrepair was significantly reduced compared with that at baseline (14.5 ± 4.4% vs 28.6% ± 3.4%; P = .037). There was no change in peak velocity, peak gradient, or mean gradient across the valve pre- versus postrepair: 293.3 ± 18.3 cm/sec versus 325.3 ± 58.2 cm/sec (P = .29), 34.3 ± 4.2 mm Hg versus 43.3 ± 15.4 mm Hg (P = .30), and 11 ± 1 mm Hg versus 9.3 ± 2.5 mm Hg (P = .34), respectively. CONCLUSIONS An ex vivo bicuspid aortic valve model was designed that recapitulated the most common human phenotype with aortic regurgitation. These valves were successfully repaired, validating its potential for evaluating valve hemodynamics and optimizing surgical repair for bicuspid aortic valves.
Tissue Engineering Part A
Cell sheet technology using UpCell™ plates is a modern tool that enables the rapid creation of a ... more Cell sheet technology using UpCell™ plates is a modern tool that enables the rapid creation of a single-layered cells without using extracellular matrix enzymatic digestion. Although this technique has the advantage of maintaining a sheet of cells without needing artificial scaffolds, these cell sheets remain extremely fragile. Collagen, the most abundant extracellular matrix component, is an attractive candidate for modulating tissue mechanical properties given its tunable property. In this study, we demonstrated rapid mechanical property augmentation of human dermal fibroblast cell sheets after incubation with bovine type I collagen for 24 hours on UpCell™ plates. We showed that treatment with collagen resulted in increased collagen I incorporation within the cell sheet without affecting cell morphology, cell type, or cell sheet quality. Atomic force microscopy measurements for controls, and cell sheets that received 50µg/mL and 100µg/mL collagen I treatments revealed an average Young's modulus of their respective intercellular regions: 6.6±1.0, 14.4±6.6, and 19.8±3.8 kPa during the loading condition, and 10.3±4.7, 11.7±2.2, and 18.1±3.4 kPa during the unloading condition. This methodology of rapid mechanical property augmentation of a cell sheet has a potential impact on cell sheet technology by improving the ease of construct manipulation, enabling new translational tissue engineering applications.