To date, the reconstructive approach addressing chronic non-healing wounds, deep tissue damage, and severe wound defects relies upon avascular dermal grafts and autologous flap techniques. Such flaps are limited by donor site availability and morbidity, while current dermal grafts rely upon host cellular invasion for neovascularization and incorporation. These products fail to include an inherent vascular network and the supporting cells necessary to ensure adequate incorporation and graft survival beyond the most optimal wound beds. Herein, we fabricate a pre-vascularized full-thickness cellularized skin equivalent containing a three-dimensional vascularized network of interconnected macro and microchannels lined with vascular cells, within a collagen neodermis populated with fibroblasts, and an epidermis comprised of human keratinocytes capable of providing whole tissue perfusion. Previously, our lab has employed a sacrificial microfiber technique to develop tissue-engineered scaffolds with an inherent hierarchical network of microvessels, which recapitulates the organization of an arteriole, venule, and capillary bed. Utilizing a type-I collagen hydrogel matrix, vascular cells were seeded within pre-fabricated channels and allowed to proliferate to generate an endothelialized microvasculature. These collagen scaffolds were subsequently anastomosed into rat models to demonstrate the clinical feasibility of such approach. The present study aims to more closely recapitulate the in vivo structure of human skin via the incorporation of vital epidermal and dermal components of native skin into a biocompatible construct containing a complex hierarchical vasculature, which may be anastomosed using standard microsurgical techniques and immediately perfused. Pluronic F127 was used as the sacrificial material: 1.5 mm diameter “U” shaped macrofibers and 100-500 µm-interwoven microfibers were heat extruded and then embedded within type-I collagen into which Cyan Fluorescent Protein (CFP)-tagged human placental pericytes and human foreskin fibroblasts (HFF1) had been encapsulated. Following pluronic sacrifice, resultant channels were intraluminally seeded with Red Fluorescent Protein (RFP)-tagged human aortic smooth muscle cells, Green Fluorescent Protein (GFP)-tagged human umbilical vein endothelial cells, and topically seeded with human epidermal keratinocytes (HEK). Construct microstructure was analyzed using multiphoton microscopy (MPM) after 7, 14 and 28 days of culture. Additionally, after 14 and 28 days of culture, endothelial cells were extracted from the construct using collagenase digestion and Real Time (RT)-qPCR performed to analyze expression of markers of angiogenesis and maturation of the vascular network. MPM demonstrated a hierarchical vascular network containing macro and microvessels lined by endothelial and smooth muscle cells, supported by perivascular pericytes, all in appropriate microanatomic arrangement. Neodermal HFF1 proliferated throughout the observation period and the HEK neoepidermis developed into a stratified epidermis along the superior aspect of the construct. Angiogenic sprouting from the nascent vascular network into neovessel like structures was noted. RT- qPCR revealed relative expression of Jagged1, Dll4, Ve-Cadherin, and CD31. We have successfully fabricated a novel tissue-engineered pre-vascularized full thickness skin flap, which recapitulates the inherent hierarchical vasculature found within human skin and is suitable for in vivo perfusion. We provide the platform for an on- demand, geometrically tunable tissue engineered skin equivalent with an anastomosable vascular network. This tissue-engineered skin flap holds the potential to transform reconstructive surgical practice by eliminating the consequences of donor site morbidity, and enabling rationally designed, patient-specific flaps for each unique wound environment and anatomic location. / 2017-06-16T00:00:00Z

Reconstructive flaps are a mainstay form of treatment for anatomical defects in plastic surgery, and despite extensive progress in the areas of flap anatomy and design, the mechanism of flap healing and the factors that regulate this process are poorly understood. This thesis investigates the regulation of flap healing, and tests the hypothesis that the introduction of genes for angiogenic growth factors can be used to augment the vascularisation and wound healing of ischaemic flaps. Using a modified McFarlane ischaemic skin flap model in Sprague Dawley rats, endogenous angiogenic regulatory factors that included the VEGF and angiopoietin families and their receptors were investigated. Twelve specific quantitative real-time PCR assays documented a general up-regulation of angiogenic genes and their receptors with time following flap elevation. There was not a readily identifiable “master regulator”. Angiogenic protein levels were more variable with a decrease VEGF-A and TNF-α levels along the flap. Debridement studies of the necrotic distal flaps demonstrated for the first time that VEGF-A164 and TNF-α protein levels stabilised, while angiogenic genes of VEGF-A164, VEGF-A120, angiopoietins and their receptors were down-regulated and VEGF-B186 and HIF-1α mRNA increased, compared to non-debrided flaps. Leucocyte proteolysis in devitalised tissue is discussed as a possible mechanism for reduced angiogenic proteins levels in ischaemic flaps. The impact of angiogenic gene therapy using adenoviral vectors in the flap model revealed for the first time that recombinant adenoviruses containing the VEGF-B186 transgene could significantly augment neovascularisation and improve flap survival. This neovascularisation correlated with up-regulation of the expression of multiple endogenous angiogenic genes that included VEGF-A164, the angiopoietins and their receptors. Erythematous plaques were documented as a side effect of Ad VEGF-A165 and Ad VEGF-B186 treatment of rat skin, although in the latter treatment they were very mild. Weals induced by the presence of VEGF-A165 transgene were associated with a marked acute inflammatory cell infiltrate and oedema consistent with the increased vascular permeability effects of VEGF-A165. Ad VEGF-A165 plus Ad ANG-1* induced weals were less prominent with reduced oedema highlighting the stabilising effect of Ad ANG-1* on vascular permeability.

The purpose of this study was to create a proof-of-concept piezoelectric actuator system capable of meeting the performance requirements necessary for actuation of a trailing edge flap for a helicopter main rotor blade. Due to extremely small displacements produced by piezoelectric actuators, their output is amplified several times in order to produce the required displacement for this device. The amplification is accomplished in two stages. The first stage, mechanical amplification, uses differential length lever arms to increase the piezoelectric actuator output. The second stage, hydraulic amplification, is coupled to the first stage and uses differential area pistons to further amplify the output of the mechanical amplifier. The actuation systems force and displacement output is characterized based on frequency.

No description available.

Reconstructive flaps are a mainstay form of treatment for anatomical defects in plastic surgery, and despite extensive progress in the areas of flap anatomy and design, the mechanism of flap healing and the factors that regulate this process are poorly understood. This thesis investigates the regulation of flap healing, and tests the hypothesis that the introduction of genes for angiogenic growth factors can be used to augment the vascularisation and wound healing of ischaemic flaps. Using a modified McFarlane ischaemic skin flap model in Sprague Dawley rats, endogenous angiogenic regulatory factors that included the VEGF and angiopoietin families and their receptors were investigated. Twelve specific quantitative real-time PCR assays documented a general up-regulation of angiogenic genes and their receptors with time following flap elevation. There was not a readily identifiable “master regulator”. Angiogenic protein levels were more variable with a decrease VEGF-A and TNF-α levels along the flap. Debridement studies of the necrotic distal flaps demonstrated for the first time that VEGF-A164 and TNF-α protein levels stabilised, while angiogenic genes of VEGF-A164, VEGF-A120, angiopoietins and their receptors were down-regulated and VEGF-B186 and HIF-1α mRNA increased, compared to non-debrided flaps. Leucocyte proteolysis in devitalised tissue is discussed as a possible mechanism for reduced angiogenic proteins levels in ischaemic flaps. The impact of angiogenic gene therapy using adenoviral vectors in the flap model revealed for the first time that recombinant adenoviruses containing the VEGF-B186 transgene could significantly augment neovascularisation and improve flap survival. This neovascularisation correlated with up-regulation of the expression of multiple endogenous angiogenic genes that included VEGF-A164, the angiopoietins and their receptors. Erythematous plaques were documented as a side effect of Ad VEGF-A165 and Ad VEGF-B186 treatment of rat skin, although in the latter treatment they were very mild. Weals induced by the presence of VEGF-A165 transgene were associated with a marked acute inflammatory cell infiltrate and oedema consistent with the increased vascular permeability effects of VEGF-A165. Ad VEGF-A165 plus Ad ANG-1* induced weals were less prominent with reduced oedema highlighting the stabilising effect of Ad ANG-1* on vascular permeability.

Made available in DSpace on 2014-06-11T19:23:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-19Bitstream added on 2014-06-13T18:14:47Z : No. of bitstreams: 1 sereno_mg_me_botfmvz.pdf: 1605062 bytes, checksum: 6cebcd988615b0290bc4972f77b75aa2 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O comprometimento anatômico e funcional das pálpebras, por afecções congênitas ou adquiridas, pode repercutir na integridade do bulbo ocular. Entre as técnicas de cirurgia reconstrutivas disponíveis, os retalhos de padrão axial têm a vantagem de possuir o suprimento sanguíneo intrínseco, assegurando irrigação adequada. Quando há a possibilidade de complicações isquêmicas, a aplicação da terapia por ondas de choque extracorpóreas (TOCE) é descrita como técnica de salvamento de retalhos. Na literatura veterinária consultada não há relatos da utilização do retalho de padrão axial oris angularis para a reconstrução palpebral, assim como da aplicação da TOCE como técnica de salvamento do mesmo na região facial periorbitária. O presente trabalho tem como objetivos avaliar a utilização do retalho axial oris angularis, na reconstrução de defeitos experimentais da pálpebra inferior de cães e verificar a atuação da terapia por ondas de choque extracorpóreas (TOCE) nos retalhos, bem como comparar os resultados clínicos e oftalmológicos do retalho com e sem a aplicação da terapia por ondas de choque. Foram utilizados oito cães, os quais foram submetidos ao desenvolvimento experimental do retalho oris angularis para a correção do defeito palpebral; estes foram avaliados por meio de exame clínico e oftalmológico até o período final de 60 dias. A avaliação histológica e morfométrica de amostras de pele submetidas ou não à TOCE, obtidas da região distal do retalho axial, aos 10 dias do pós-operatório, também foi realizada. O retalho de padrão axial oris angularis apresentou resultados funcionais e cosméticos favoráveis em cães. A TOCE, nos parâmetros utilizados e na região periocular, não apresentou diferença de atuação significativa como técnica de salvamento quando comparada à confecção isolada do retalho oris angularis... / The functional and anatomical compromise of the eyelids by congenital or acquired affections, can affect the integrity of the eye bulb, making necessary reconstructive surgeries techniques. Among the available techniques, axial flaps patterns where describe to cover facial defects, being its vascularization intrinsic, considered an advantage to other techniques, ensuring the appropriate vascularization, and also preserving the facial esthetics. Considering isquemic complications extracorporeal shockwave therapy (ESWT) was described such rescue technique on compromised skin flaps. There are not any veterinary references to use of an oris angularis skin flap to eyelid reconstruction as well ESWT in facial areas. The present study was developed to evaluate the oris angularis axial flap clinical performance on dogs’ eyelids experimental defects reconstruction, and ESWT applicability over the distal end of the axial flap. The ophthalmologic exam was performed to determine possible prejudicial interactions between the treatments used and the eye. Eight dogs were ophthalmologic and clinically evaluated for sixty days. The skin samples treated or not with the shock wave therapy, obtained from flap’s distal border, where analyzed histological and with morfometry. The oris angularis axial skin flap presented good results, functional and esthetical, on the experimental repair of the dog’s eyelids. The ESWT with the protocol used in this study, did not demonstrate significant clinical outcomes as a rescue technique when applied over the oris angularis flap, however results showed no signals of collateral deleterious effects. The flap with or without ESWT did not show any histological sign of inflammatory or atrophic alterations. Both group treated showed similar morphometrical characteristics. The axial oris angularis skin flap was also used to repair large defects on the eyelids and nasal... (Complete abstract click electronic access below)

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22328号 / 医博第4569号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 椛島 健治, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22349号 / 医博第4590号 / 新制||医||1042(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 椛島 健治, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This project examined the effect of Gurney flaps on a 2D, 2-ft chord NACA 0036 airfoil in the Cal Poly 3’x4’ low speed wind tunnel at 25 m/s. It also covered the numerical simulation of the experiment in computational fluid dynamics (CFD). During the study, problems with the wind tunnel data were seen. After a careful diagnosis, the problem was traced to dirty flow conditioners which were subsequently replaced. Five Gurney flaps at 1, 2, 3, 4, and 5% of the chord were tested. The Gurney flaps had the effect of eliminating the lift reversal effect and lowering the profile drag at low angles of attack, ranging from 4-27%. The optimal Gurney flap appeared to be 2% of the chord. CFD modeling of the problem had limited success, with the best results coming from Mentor’s k-w SST turbulence model. This model reproduced the non-linear lift curve, and captured the trend in rising drag fairly well, but failed to predict the correct point of separation. Attempts to model the Gurney flap in CFD were unsuccessful.

Magister Chirurgiae Dentium (MChD) / Introduction: Defects in the mandible and maxilla have various etiological factors. These include trauma, inflammatory diseases or pathology such as benign and malignant tumours. Patients that are exposed to these factors are often left with compromised function and aesthetics which could have a deleterious effects on the patients’ quality of life if not adequately restored with reconstructive surgery (Goh et al. 2008). Reconstruction should aim to allow rehabilitation of normal stomatognathic function, facial contour and aesthetics, obliteration of dead space left after ablation, and the need to examine the area for recurrence (Kim and Ghali 2011). The fibula free flap has become the gold standard for maxillofacial reconstruction. This flap offers various advantages that makes it suitable, especially for reconstructing defects of the mandible (Anne-Gaelle et al. 2011). The success of rehabilitation of these patients should however also take into consideration the patient’s ability to use a dental prosthesis (conventional or implant retained) post-operatively. This remains challenging (Kramer and Dempf 2005). The effective placement of a dental prosthesis relies on the basic principles of retention, stability and support. With the altered anatomy caused by the graft, placement of dental implants is used to enhance retention and stability. Quality of life (QoL) is a measure of a patient’s satisfaction with their current situation in regards to function and other factors compared to a perceived or expected ideal. The subjective component linked to quality of life means that it could vary from one locality to another, and therefore gathering data that will establish a baseline for these patients that have undergone tumour ablative surgeries. This could be invaluable to healthcare practitioners that operate in this specific field.