Thiel embalmed cadaveric tissue : a model for surgical simulation and research

Le Collège royal des médecins et chirurgiens du Canada met actuellement en place des curriculums basés sur les compétences, plutôt que sur le temps, dans toutes les spécialités médicales et chirurgicales. La transition devrait être complétée en 2022. Les programmes de formation en chirurgie plastique au Canada devront repenser leurs curriculums pour se plier aux directives nationales. La simulation est la pierre angulaire du modèle de formation des résidents basé sur les compétences puisqu'elle permet aux résidents d'apprendre et d'améliorer leurs compétences dans un contexte éthique, sécuritaire, et mesurable objectivement. Un consensus récent des directeurs de programme canadiens en chirurgie plastique a nommé 154 procédures essentielles de bases que les résidents doivent maîtriser avant la fin de leur formation. Nous proposons l'utilisation du modèle cadavérique Thiel pour la simulation haute fidélité des procédures en plastie. Les spécimens Thiel ont déjà été introduits dans une multitude de spécialités, incluant la plastie pour la dissection de lambeaux et la réparation de tendons. Nous nous sommes concentrés sur l'évaluation des spécimens Thiel pour la maîtrise des anastomoses vasculaires, la réparation des nerfs périphériques, et la réparation des tendons fléchisseurs. Par ailleurs, nous avons développé des instruments d'évaluation pour chacun de ces domaines de simulation. Des trois instruments, nous avons validé les échelles d'évaluation des anastomoses vasculaires et nerveuses. Ces deux échelles ont démontré d'excellents degrés de fiabilité et de reproductibilité et sont bien corrélés avec le niveau de formation et d'expérience des sujets. Le modèle de réparation des tendons fléchisseurs a démontré un degré plus élevé de variaiblité inter-évaluateur, et, quoique prometteur, il n'a pas pu être complètement validé basé sur les données actuelles. De plus, nous avons utilisé les vaisseaux Thiel comme un modèle de recherche pour l'investigation de nouvelles techniques microvasculaires. Notre expérience montre que les spécimens cadavériques Thiel sont un excellent modèle de simulation pour la chirurgie microvasculaire et la réparation des nerfs périphériques et des tendons fléchisseurs. Nous proposons des instruments d'évaluation pour assister à l'implémentation de ces modèles de simulation dans les curriculums basés sur les compétences en chirurgie plastique.The Royal College of Physicians and Surgeons is currently implementing a major shift from a time based to a competence based curriculum in all medical and surgical specialties. By 2022 the transition is to be complete. The plastic surgery training programs in Canada will have to rethink their curriculum in order to comply with the national directives. Simulation is a cornerstone of the competence based model of resident training as it not only allows residents to safely learn and hone their skill in a setting that is ethical and promotes patient safety, but it allows for objective evaluation of their performance. A recent consensus statement from the Canadian plastic surgery program directors identified 154 essential core procedures for residents to master by the end of their training. We propose the use of the Thiel cadaveric model for high fidelity simulation of plastic surgery procedures. While Thiel cadaveric specimens have been proposed for use in a multitude of specialties, including in plastic surgery for flap dissection and tendon repair, we focused on evaluating the use of the Thiel embalmed specimens on three core procedures: microvascular anastomoses, peripheral nerve repair, and flexor tendon repair. In addition, we designed evaluation instruments for each of these three simulation areas to help grade performance and aid in the feedback/debriefing process. Of the three evaluation instruments, we successfully validated the microvascular evaluation and micro-neurorrhaphy evaluation scales. Both of these scales showed excellent degrees of reliability and reproducibility and correlated well with the level of training and self-declared experience of the subjects. The flexor tendon evaluation scale showed a higher degree of inter-rater variability and, while it shows promise with a larger cohort of participants and additional calibration, it could not be validated fully based on the available data. Additionally, we used the Thiel embalmed cadaveric vessels as a research model for the investigation of new microvascular techniques. Our experience shows the Thiel cadaveric specimens to provide an excellent model for simulating microvascular, peripheral nerve and flexor tendon repairs. We propose evaluation instruments to assist in the implementation of these simulation models in a comprehensive, competence based curriculum in plastic surgery

Developing and Modeling Scaffold Free Vascular Constructs

Despite a strong clinical demand for tissue replacement therapies, few tissue-engineered constructs (TECs) have attained FDA approval. Fewer still demonstrate long term viability of implanted cells, with root causes of failure of these devices identified as poor cell retention, poor vascularization, and inflammation following implantation. Focusing on the first two of these issues, we attempt to create a rapidly vascularizable TEC by optimizing a novel vascular implant model developed in our laboratory: the scaffold-free, prevascular endothelial-fibroblast construct (SPEC). The optimization process calls on a hybrid in vivo, in vitro, and in silico approach. We first developed an in vivo temporal model of TEC vascularization by comparing endothelial invasion, cord development, anastomosis, and vessel maturation dynamics of SPECs to avascular grafts such as fibroblast-only spheroids and silicone implants. While the existing microvessel architecture of the SPECs confers an advantage in anastomosis and endothelial infiltration of an implant in the first 12 hours post-implantation, poor lumen patency limits the rate of vessel development in the TECs. Perfusion is apparent at later time points (24-72 h) in both SPECs and fibroblast-only spheroids. Analysis of in vivo vascularization dynamics is augmented by a control flow simulation model which reveals that delayed vascular development coincides with poor accumulation of pro-angiogenic factors such as VEGF. Our in vivo observations drove corrections of our SPEC model, with efforts undertaken to improve lumen formation during the in vitro development period. These approaches include pre-dosing implants with pro-angiogenic factors such as VEGF, inducing endothelial cell realignments in a perfusion chamber, and incorporation of perivascular cells to improve patency of forming tubes. Recombinant human VEGF165 (rhVEGF165) dosing was most consistently associated with increased formation of endothelial-lined lumens, with a dose (ranging from 0-50 ng/mL) and time dependent increase in diameters of these lumens during SPEC formation. Finally, we generated computational models of SPEC formation in a rhVEGF165 field in order to combine our observations of endothelial clustering behavior, SPEC reorganization, and dose/time dependent cord hollowing behavior observed in vitro with existing stochastic models of tissue assembly and cell-cell interface optimization. Through careful control of model parameters, we generated a list of in silico simulations to enable optimization of vascularization response, ultimately resulting in a list of candidate treatments built on the backbone of VEGF pre-dosing. This candidate list can serve as a starting point for future experiments, with a goal of rapid and stable lumen formation and blood perfusion

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

Intraoperative Fourier domain optical coherence tomography for microsurgery guidance and assessment

In this dissertation, advanced high-speed Fourier domain optical coherence tomography (FD-OCT)systems were investigated and developed. Several real-time, high resolution functional Spectral-domain OCT (SD-OCT) systems capable of imaging and sensing blood flow and motion were designed and developed. The system were designed particularly for microsurgery guidance and assessment. The systems were tested for their ability to assessing microvascular anastomosis and vulnerable plaque development. An all fiber-optic common-path optical coherence tomography (CP-OCT) system capable of measuring high-resolution optical distances, was built and integrated into di fferent imaging modalities. First, a novel non-contact accurate in-vitro intra-ocular lens power measurement method was proposed and validated based on CP-OCT. Second, CP-OCT was integrated with a ber bundle based confocal microscope to achieve motion-compensated imaging. Distance between the probe and imaged target was monitored by the CP-OCT system in real-time.The distance signal from the CP-OCT system was routed to a high speed, high resolution linear motor to compensate for the axial motion of the sample in a closed-loop control. Finally a motion-compensated hand-held common-path Fourier domain optical coherence tomography probe was developed for image-guided intervention. Both phantom and ex vivo models were used to test and evaluate the probe. As the data acquisition speed of current OCT systems continue to increase, the means to process the data in real-time are in critically needed. Previous graphics processing unit accelerated OCT signal processing methods have shown their potential to achieve real-time imaging. In this dissertation, algorithms to perform real-time reference A-line subtraction and saturation artifact removal were proposed, realized and integrated into previously developed FD-OCT system CPU-GPU heterogeneous structure. Fourier domain phase resolved Doppler OCT (PRDOCT) system capable of real-time simultaneous structure and flow imaging based on dual GPUs was also developed and implemented. Finally, systematic experiments were conducted to validate the system for surgical applications. FD-OCT system was used to detect atherosclerotic plaque and drug effi ciency test in mouse model. Application of PRDOCT for both suture and cu ff based microvascular anastomosis guidance and assessment was extensively stuided in rodent model

Thermal Fusion for Sutureless Closure: Devices, Composition, Methods

As minimally invasive surgical techniques progress, the demand for reliable ligation is pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. While the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used between devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue bond. Further, energy-based techniques (e.g., tissue “fusion” or tissue “welding”) exhibit promise for the closure, repair and functional recovery of soft and connective tissues in the orthopaedic, colorectal and dermal domains. To optimize and progress the use of energy-based tissue fusion, a constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required. While rapid tissue bonding may arise from dehydration and water transport, dipole interactions, covalent crosslinks or the coagulation of cellular proteins, long-term tissue repair requires that the reaction to thermal damage be tailored to accelerate and mimic the onset of biological healing and remodeling. The aim of this work is to supplement the findings of published thermal fusion research by exploring the contributions of primary and secondary tissue constituents to the formation of energy-based fusion bonds. Results of this work and their associated implications to the theory of energy-based surgical adhesion will encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond

DEVELOPMENT OF NANOPARTICLE RATE-MODULATING AND SYNCHROTRON PHASE CONTRAST-BASED ASSESSMENT TECHNIQUES FOR CARDIAC TISSUE ENGINEERING

Myocardial infarction (MI) is the most common cause of heart failure. Despite advancements in cardiovascular treatments and interventions, current therapies can only slow down the progression of heart failure, but not tackle the progressive loss of cardiomyocytes after MI. One aim of cardiac tissue engineering is to develop implantable constructs (e.g. cardiac patches) that provide physical and biochemical cues for myocardium regeneration. To this end, vascularization in these constructs is of great importance and one key issue involved is the spatiotemporal control of growth-factor (GF)-release profiles. The other key issue is to non-invasively quantitatively monitor the success of these constructs in-situ, which will be essential for longitudinal assessments as studies are advanced from ex-vivo to animal models and human patients. To address these issues, the present research aims to develop nanoparticles to modulate the temporal control of GF release in cardiac patches, and to develop synchrotron X-ray phase contrast tomography for visualization and quantitative assessment of 3D-printed cardiac patch implanted in a rat MI model, with four specific objectives presented below. The first research objective is to optimize nanoparticle-fabrication process in terms of particle size, polydispersity, loading capacity, zeta potential and morphology. To achieve this objective, a comprehensive experimental study was performed to examine various process parameters used in the fabrication of poly(lactide-co-glycolide) (PLGA) nanoparticles, along with the development of a novel computational approach for the nanoparticle-fabrication optimization. Results show that among various process parameters examined, the polymer and the external aqueous phase concentrations are the most significant ones to affect the nanoparticle physical and release characteristics. Also, the limitations of PLGA nanoparticles such as initial burst effect and the lack of time-delayed release patterns are identified. The second research objective is to develop bi-layer nanoparticles to achieve the controllable release of GFs, meanwhile overcoming the above identified limitations of PLGA nanoparticles. The bi-layer nanoparticle is composed of protein-encapsulating PLGA core and poly(L-lactide) (PLLA)-rate regulating shell, thus allowing for low burst effect, protein structural integrity and time-delayed release patterns. The bi-layer nanoparticles, along with PLGA ones, were successfully fabricated and then used to regulate simultaneous and/or sequential release of multiple angiogenic factors with the results demonstrating that they are effective to promote angiogenesis in fibrin matrix. The third objective is to develop novel mathematical models to represent the controlled-release of bioactive agents from nanoparticles. For this, two models, namely the mechanistic model and geno-mechanistic model, were developed based on the local and global volume averaging approaches, respectively, and then validated with experiments on both single- and bi-layer nanoparticles, by which the ovalbumin was used as a protein model for the release examination. The results illustrates the developed models are able to provide insight on the release mechanism and to predict nanoparticle transport and degradation properties of nanoparticles, thus providing a means to regulate and control the release of bioactive agents from the nanoparticles for tissue engineering applications. The fourth objective of this research is to develop a synchrotron-based phase contrast non-invasive imaging technique for visualization and quantitative assessment of cardiac patch implanted in a rat MI model. To this end, the patches were created from alginate strands using the three-dimensional (3D) printing technique and then surgically implanted on rat hearts for the assessment based on phase contrast tomography. The imaging of samples was performed at various sample-to-detector distances, CT-scan time, and areas of the region of interest (ROI) to examine their effects on imaging quality. Phase-retrieved images depict visible and quantifiable structural details of the patch at low radiation dose, which, however, are not seen from the images by means of dual absorption-phase and a 3T clinical magnetic resonance imaging. Taken together, this research represents a significant advance in cardiac tissue engineering by developing novel nano-guided approaches for vascularization in myocardium regeneration as well as non-invasive and quantitative monitoring techniques for longitudinal studies on the cardiac patch implanted in animal model and eventually in human patients