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Honaker, Jeremy Seth. "Predictors of wound healing in lower extremity wounds". Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1491492683015683.
Pełny tekst źródłaErrington, Rachel J. "In vitro wound healing". Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357419.
Pełny tekst źródłaUnderdown, Mary Jane. "Antioxidants and Wound Healing". Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/honors/65.
Pełny tekst źródłaWeber, Sonja A. "Electrical Characterisation of Wounds and Stimulation of Wound Healing". Thesis, University of Ulster, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516428.
Pełny tekst źródłaHead, Cynthia C. "Hormonal regulation of cutaneous wound healing effect of androstenediol on stress-impaired wound healing /". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1186957947.
Pełny tekst źródłaDoshi, Anuja. "Topical Phenytoin Effects on Palatal Wound Healing". The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563487879484746.
Pełny tekst źródłaSherratt, Jonathan Adam. "Mathematical models of wound healing". Thesis, University of Oxford, 1991. https://ora.ox.ac.uk/objects/uuid:4e3ea7dd-33c6-4696-a2ec-aa3499c8b3f6.
Pełny tekst źródłaLoots, Miriam Alfonsa Maria. "Wound healing in diabetic ulcers". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/66897.
Pełny tekst źródłaMcCluskey, Jane T. "Mechanisms of embryonic wound healing". Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318851.
Pełny tekst źródłaBailey, Matthew John. "Protein changes in wound healing". Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427693.
Pełny tekst źródłaRippon, Mark Geoffrey. "The physiology of wound healing". Thesis, Manchester Metropolitan University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240980.
Pełny tekst źródłaMcHugh, Jolene. "Sensors for monitoring wound healing". Thesis, Ulster University, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686440.
Pełny tekst źródłaRamier, James Charles. "Biomechanics of corneal wound healing /". Online version of thesis, 1992. http://hdl.handle.net/1850/10786.
Pełny tekst źródłaWalters, Kyle D. "Wound healing in Caribbean sponges /". Electronic version (PDF), 2003. http://dl.uncw.edu/etd/2003/waltersk/kylewalters.html.
Pełny tekst źródłaKanapathy, M. "Translational studies in wound healing". Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1569432/.
Pełny tekst źródłaOu, Jingxing. "Chronic wound state associated with cytoskeletal defects and exacerbated by oxidative stress in Pax6+/- aniridia-related keratopathy". Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=25200.
Pełny tekst źródłaCook, Julian. "Mathematical models for dermal wound healing : wound contraction and scar formation /". Thesis, Connect to this title online; UW restricted, 1995. http://hdl.handle.net/1773/6756.
Pełny tekst źródłaIsotupa, Christine. "PTSD as a social wound, do social wounds require social healing?" Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ51201.pdf.
Pełny tekst źródłaGan, Lisha. "Corneal cellular proliferation and wound healing /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4505-5/.
Pełny tekst źródłaGiannelis, Georgios. "Matrix metalloproteinases in scarless wound healing". Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/36241.
Pełny tekst źródłaLeBlanc, Sarah. "CEACAM1 deficiency delays cutaneous wound healing". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66794.
Pełny tekst źródłaCEACAM1 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1) est exprimé à la surface de nouveaux vaisseaux sanguins de tissus en prolifération ou de tumeurs humaines, et est associé aux stades précoces de l'angiogenèse. De plus, CEACAM1 semble être un puissant facteur angiogénique en potentialisant l'activité du VEGF in vivo. Malgré de nombreuses observations, le rôle de CEACAM1 dans l'angiogenèse normale reste à définir. Dans ce contexte, nous avons réalisé des essais de cicatrisation cutanée dans des souris Ceacam1-/-. Des plaies de 6 mm ont été effectuées sur le dos des souris. La vitesse de cicatrisation a été suivie sur 10 jours, et les plaies ont été examinées en histologie 3, 7 et 10 jours après l'essai. D'un point de vue macroscopique, la délétion de CEACAM1 n'a pas d'effet sur la cicatrisation des plaies. En revanche, des analyses plus précises en histologie montrent que la cicatrisation des souris Ceacam1 -/- est différée. En effet, le mécanisme de re-épithélisation des plaies des souris Ceacam1 -/- est retardé aux points 3 et 7 jours après blessure. De plus, l'inflammation des plaies des souris Ceacam1 -/- est également affectée : l'infiltration des macrophages F4/80+ au sein des plaies 7 et 10 jours après blessure, ainsi que celle des mastocytes au point 7 jours après blessure sont significativement diminuées. Enfin, la densité vasculaire des plaies Ceacam1-/- est également réduite de façon significative. En revanche, l'expression de VEGF au sein des plaies ne semble pas altérée. Les résultats de cette étude confirment le rôle de CEACAM1 dans l'angiogenèse, mais présentent de façon plus importante CEACAM1 comme un facteur clé dans le mécanisme de cicatrisation des plaies cutanées.
Liao, Laura. "Signalling in single cell wound healing". Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44784.
Pełny tekst źródłaWaugh, Helen Victoria. "Mathematical models of diabetic wound healing". Thesis, Heriot-Watt University, 2007. http://hdl.handle.net/10399/99.
Pełny tekst źródłaBannon, Pauline. "Activation of macrophages during wound healing". Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/activation-of-macrophages-during-wound-healing(28ce7af3-3516-43ed-b0e0-93995691e1ac).html.
Pełny tekst źródłaWestgate, Samantha Jane. "Biofilms and chronic equine wound healing". Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569171.
Pełny tekst źródłaFlegg, Jennifer Anne. "Mathematical modelling of chronic wound healing". Thesis, Queensland University of Technology, 2009. https://eprints.qut.edu.au/40164/1/Jennifer_Flegg_Thesis.pdf.
Pełny tekst źródłaCoutin, Julia Viviana. "Cefazolin Concentration in Surgically Created Wounds Treated with Negative Pressure Wound Therapy Compared to Surgically Created Wounds Treated with Nonadherent Wound Dressings". Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/49112.
Pełny tekst źródłaMaster of Science
Shen, Yue. "Plasminogen : a novel inflammatory regulator that promotes wound healing". Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-68755.
Pełny tekst źródłaPawar, Harshavardhan Vilasrao. "Development and characterisation of medicated wound dressings for chronic wound healing". Thesis, University of Greenwich, 2013. http://gala.gre.ac.uk/11952/.
Pełny tekst źródłaDale, Paul David. "Time heals all wounds? : mathematical models of epithelial and dermal wound healing". Thesis, University of Oxford, 1995. http://ora.ox.ac.uk/objects/uuid:aaa4717f-a115-4a34-bb03-d64ce81841d9.
Pełny tekst źródłaJacobsson, Lena. "Evaluation of Novel Materials for Wound Healing". Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-16592.
Pełny tekst źródłaRapid wound healing is important to regain the skins protective function after injury. Studies have shown that enamel matrix proteins (EMP) have many desirable effects which may accelerate wound healing [Bosshardt et al. 2008].
Polymers (Polymer A, B and C) were formed into a mat form, with or without incorporated enamel matrix derivative (EMD) (Collaboration partner). The materials may be suitable for wound care and drug delivery systems.
Protein release tests were performed on samples incubated in physiological-like solution using pyrogallol red staining, ultraviolet (UV) spectrophotometer and high-performance liquid chromatography (HPLC). Protein was detected in Polymer A material samples, compared to a reference material sample, using pyrogallol red staining. An in vitro experiment showed that normal human dermal fibroblasts (NHDF) cultivated with Polymer A material (with EMD) had significantly higher viability than NHDF cultivated with reference material (Polymer A without EMD) and comparable viability to fibroblasts grown with either 0.1 mg EMD in solution or with 10% fetal calf serum. Images taken of Polymer A material, with incorporated Fluorescein isothiocyanate- (FITC) labeled EMD, indicate a homogenous distribution of EMD peptides and/or EMD aggregates throughout the material. A dressing which contains an active substance may have clinical promise for wound care applications.
Koskela, M. (Marjo). "Wound healing and skin in severe sepsis". Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526214269.
Pełny tekst źródłaTiivistelmä Sepsiksen ajatellaan heikentävän haavanparanemista, mutta tieteellistä näyttöä on niukasti. Iholla on keskeinen osa elimistön puolustuksessa ja tasapainon ylläpidossa, joten sen toiminnan häiriintyminen systeemisessä tulehduksessa ansaitsee suuremman huomion. Imurakkulahaavat tehtiin 44 septiselle potilaalle ja 15 kontrollille. Haavoista mitattiin veden haihtumista ja veren virtausta sekä otettiin imurakkulaneste näytteeksi sytokiinimäärityksiä varten. Tutkimuksen ensimmäisenä ja kahdeksantena päivänä otettiin 4mm biopsiat terveeltä iholta ja 15 potilaalta poistettiin näytteeksi paraneva imurakkulahaava. Seeruminäytteet otettiin tutkimuksen ensimmäisenä päivänä. Veden haihtuminen haavalta oli voimakkaampaa eli ihon barrierin palautuminen oli hidastunut septisillä potilailla verrattuna kontrolleihin. Haavassa havaittu tulehdus oli sepsiksessä voimakkaampi. Tyvikalvon komponenttien Laminiini-332:n ja tyypin IV kollageenin ilmentyminen oli vähäisempää sepsiksen aikana ja lisääntyi 3kk kohdalla, mutta ei kuitenkaan saavuttanut kontrollien tasoa. Tiivisliitosproteiinien ilmentyminen oli lähes muuttumatonta sepsiksessä kontrolleihin verrattuna. Okludiinin ilmentyminen sen sijaan paranevassa haavassa vaeltavien keratinosyyttien etureunassa oli rajoittuneempaa ja myöhäisempää sepsiksessä kuin kontrolleilla. Sytokiineistä tuumorinekroositekijä (TNF), interleukiini-10 (IL-10) ja IL-6 olivat koholla imurakkulanesteessä verrattuna kontrolleihin. Epidermaalinen kasvutekijä, verisuonten endoteelikasvutekijä, TNF ja perusfibroplastinen kasvutekijä (bFGF) pitoisuudet rakkulanesteessä erosivat seerumin pitoisuuksista eli ihon sytokiiniprofiili erosi systeemisestä sytokiiniprofiilista. Potilailla, joilla oli monielinvaurio, todettiin korkeampia sytokiinipitoisuuksia. Potilailla, jotka menehtyivät 30 vrk kuluessa, oli korkeammat pitoisuudet IL-10 ja bFGF rakkulanesteessä. Tämä tutkimus tarjoaa uutta tietoa ihosta ja haavanparanemisesta sepiksessä. Tulosten perusteella voidaan todeta, että ihon toimintahäiriö on sepsiksessä todellinen, vaikka kaikkein perustavimmat rakenteet säilyvät muuttumattomina. Toimintahäiriön mekanismien ymmärtäminen voisi auttaa septisen potilaan hoidossa, kuten kirurgisten toimenpiteiden ajoittamisessa paranemisen kannalta mahdollisimman otolliseen aikaan
Szpalski, Caroline. "Co-morbidities induced vasculogenic impaired wound healing". Doctoral thesis, Universite Libre de Bruxelles, 2013. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209533.
Pełny tekst źródłaSkin wound healing (WH) is a dynamic and extremely determinate process of cellular, humoral and molecular mechanisms which begins directly after wounding and can last for years. WH is described as is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. The process of skin WH occurs through the actions of an interplay of cells, growth factors and cytokines leading to wound closure.
WH occurs in three precisely and highly programmed phases: the inflammatory phase (day 0 to day 7) followed by the proliferative phase or vasculogenic phase (day 7 to day 21) and finally the remodeling phase (2 days - up to 2 years). For a successful healing, all three phases must occur in the proper sequence and time frame.
Many factors can interfere with one or more phases of the WH process, thus causing improper or impaired healing. The proliferation phase, in particular, requires the participation of various cells types such as fibroblasts, endothelial cells (ECs) and endothelial progenitor cells (EPCs), to produce a healthy well-vascularized granulation tissue for epithelization and wound closure.
A.1 Wound Healing And Obesity
In 2008, over 1.4 billion adults, 20 and older, were overweight. Of these, obesity has been shown to affect over 500 million people (OMS website). Moreover, the prevalence of obesity continues to rise, and by 2018, it is estimated that obesity will cost $ 347 billion annually.
Each year, in the US, approximately 33 million overweight and obese patients undergo surgery. Obesity causes a number of known health problems and increased post-surgical complications such as wound infection, dehiscence, hematoma and seroma. Surgeons anecdotally report WH complications among obese patients; however, little research has been conducted to investigate the mechanisms mediating impaired obesity-related WH.
Some previous work on diabetic patients and diabetic mice showed an imbalance between pro-oxydant and anti-oxydant genes as well as impaired EPCs proliferation and tube formation during the WH process. More then a hundred cytologic factors have been found to impair WH in the type 2 diabetic patient. It is a very complex and multifactorial problem involving decreased growth factors secretion, impaired keratinocyte and fibroblast functions, impaired EPs function, alteration of the macrophage function and granulation tissue synthesis, etc.
Based on these findings and because obesity is associated with the development of type 2 diabetes, we hypothetize that, impaired balance between pro-apoptotic/anti-apoptotic and pro- oxydant /anti-oxydant genes is involved in impaired WH. Furthermore, we hypothetize that impaired EPCs function leads to the perturbation of the proliferation phase of obesity impaired WH.
A.2. Wound Healing and Age
The world population is aging; by 2030, nearly 20% of Americans, (± 72 million people), will be 65 years old and older. In 2010, 17% of the European population was over the age of 65. By 2060, it is projected that the share of those aged 65 and over will rise to 30%, accounting for more then 150 million people. (ec.europa.eu) These aging subjects undergo an increasing number of surgical procedures: in the past two decades, the percentage of surgeries in patients over 65 has doubled to nearly 40%.
As a corollary, it is well established knowledge that elderly WH is impaired. However, little is known about the underlying mechanisms of age-related impaired WH.
As previously mentioned, adult BM-derived EPCs contribute to peripheral tissue repair and regeneration. In light of the abundant literature suggesting that neovascularization is impaired in the elderly, we characterize a novel model of senile cutaneous WH and investigate the role that vasculogenesis plays in the pathogenesis of age related impaired WH.
Aged mice colonies have traditionally been the model for aged small mammalian research, however, the ability to use a readily-available transgenic mouse model with features of accelerated aging would aid in the exploration of targeted therapies and a great number of age-related investigations.
We hypothesize that the Hutchinson-Gilford Progeria Syndrome (HGPS) Zmpste24 deficient (Zmpste24-/-) mouse mimics physiological ageing and can be used as a novel model for the study of senescent WH. We further hypothetized that impaired balance between pro-apoptotic/anti-apoptotic and pro-oxydant /anti-oxydant genes as well as impaired EPCs function are responsible for the impairment of the proliferative phase, leading to overall impaired WH.
A.3 Aims
Recently, a great deal of research has been directed at understanding the critical factors inducing poorly healing wounds. However, a lot remains unclear.
It is now well accepted that new blood vessel formation occurs not only by angiogenesis (blood vessels formation from a preexisting network of capillaries), but also by vasculogenesis (blood vessels formation from BM SCs recruitment) and that EPCs contribute to as much as 25% of new blood vessels formed in healing tissues4. They are mobilized from the BM in response to injury and production of local cytokines, are incorporate into wounds and play an integral role in systemic tissue repair.
Based on this finding, we hypothesized that co-morbidities related impaired WH may be due, in part, to decreased EPCs number, migration/homing, and/or function resulting in impaired vasculogenesis. Because age and/or obesity have been shown to be one of the most common predictors of altered WH, we decided to focus on these two parameters.
Following a bedside to bench approach the purpose of this work was to 1) develop coherent and translatable models of co-morbidity digging in the physiologic/pathologic mechanisms underlying altered healing in obese and senile mice; 2) develop targeted therapeutics to improve impaired WH.
B. Material and Methods
B.1 Human Model
Since obesity impairs WH and BM EPCs are important for tissue repair, we hypothesize that obesity- impaired WH is due, in part, to impaired EPCs mobilization, trafficking, and function. Peripheral blood was obtained from non diabetic, obese (BMI > 30, n = 25), and non obese (BMI < 30, n = 17) subjects. Peripheral blood human EPCs were isolated, quantified, and functionally assessed.
As for aged impaired WH, EPCs of aged subjects have already been found to have decreased adhesion, migration and proliferative properties as well as being decreased in number in elderly patients undergoing surgery compared to younger patients.
B.2. Mice Models
Two models of WH were developed and characterized.
In order to isolate the effect of obesity on EPCs and WH, OB non-diabetic female TallyHo/JngJ mouse were selected (Female mice don’t express hyperglycemia and hyperinsulinemia). Female SWR/J non-OB mice were used as control mice. In order to limit variables, TallyHO/JngJ obese mice were selected over other OB mice that exhibit a polygenic type of obesity (Jackson Laboratory Website). By selecting this mouse model, we have excluded in our selection of the ideal model common confounding factors such as hyperglycemia, hyperinsulinemia, immune disorders.
Zmpste24 is a metalloproteinase involved in the maturation of lamin A (LmnA), an essential component of the nuclear envelope. When Zmpste24 or LmnA are knocked-out, mice exhibit profound nuclear architectural abnormalities and histopathological defects that phenocopy an accelerated aging process. Of crucial importance, the lamin-A dependent nuclear alterations seen in Zmpste24-deficient mice have also been found in human physiological aging. We defined the utilization of the Hutchinson-Gilford Progeria Syndrome (HGPS) Zmpste24 deficient (Zmpste24- /-) mouse as a novel model for the study of senescent WH (controls used were C57BL/6J mice).
B.3. Wounding Model and Data Collection
All mice group underwent wounding using a stented wound model developed in our laboratory and previously published. Briefly, paired 6-mm circular, full-thickness wounds extending through the panniculus carnosus were made on the dorsal skin of the mouse. An O-ring, 12-mm splint made of silicone sheeting was then sutured to the skin around the wound. To minimize wound contraction and reliably recapitulated the granulation and re-epithelialization seen in human WH by secondary intention. Time to wound closure was measured using standardized digital photographs taken on days 0, 7, 14, and 21. Wound closure was calculated as a percentage of the original wound.
For each model, EPCs were harvested, quantified by flow-cytometry and their function tested. Wounds were harvested at various time points and RNA, DNA and protein analysis were conducted. Finally immunohistochemistry to assess epidermal thickness, vascularity and WH were also realized.
In a second step, after characterization of the models, local (using targeted siRNA gel) and systemic therapies (using AMD3100, a PC mobilizer) were applied on the wounds and compared to controls. WH was monitored. We conducted the previously mentioned analysis (RT-PCR, ELISA and DNA analysis) on the harvested samples.
All values are expressed as a mean ± standard error of mean (SEM). The number of mice per treatment group was determined using G*Power (G*Power©, Melbourne, Australia) to provide a power greater than 0.80. Student T test was realized to compare two groups among each other.
C. Results
C.1. Human EPCs Have Impaired Function
There was no difference in the number of baseline circulating human EPCs in non-diabetic OB and non-OB
subjects, but EPCs from OB subjects had impaired adhesion (p<0.05), migration (p<0.01), and proliferation (p<0.001).
C.2. Obesity and Wound Healing
TallyHo/JgnJ OB mice demonstrated significantly impaired healing when compared to SWR/J control mice. They healed at an average of 28 ± 2 days (p<0.05). Post-wounding circulating EPCs were quantified and wounds were analyzed. Circulating EPCs recruitment is impaired in wounded TallyHo/JngJ mice and their wounds shown significantly decreased new blood vessel formation through decreased HIF-1α/SDF-1α signaling (p<0.05). Their wounds are characterized by increased apoptosis, increased DNA damage and impaired pro-/anti-oxydant balance. Immunonistochemistry and histology showed decreased vascular vessels in TallyHo/JngJ wounds and thinner epidermal thickness.
In the local treatment phase, local p53 silencing consistently improved WH to a nearly normal healing time (wounds healed in 18 ± 2 days, p<0.05). sip53 treatment showed a significant decrease in pro-apoptotic markers (p53, Bax, PUMA p<0.05) and a significant increase in angiogenic markers (VEGF, SDF-1α, HIF-1α) with increased blood vessel formation and decreased DNA damage.
C.3. Age and Wound Healing
In these experiments, we show that not only is Zmpste24-/- WH impaired when compared to C57BL/6J mice (Zmpste24-/- mice healed at average 40 days ± 2 days p<0.05) at all time points but that they also showed decreased vascularity and proliferation in the wound bed (p<0.05).
Histological analysis was performed utilizing hematoxylin and eosin staining to assess epidermal thickness, CD31 immunofluorescence to assess vascular density, p53 and caspase 3 to assess apoptosis, 8’OHdG staining to assess DNA damage and PCNA to assess proliferation. Epidermal thickness was significantly decreased in Zmpste24-/- animals compared to WT as well as vascular density, and proliferation in Zmpste24-/- wound tissue (p<0.05).
Circulating vasculogenic EPCs recruitment was impaired in Zmpste24-/- mice and their wounds showed significantly decreased new blood vessel formation through decreased HIF-1α/SDF-1α signaling (p<0.05). Zmpste24-/- wounds are characterized by increased apoptosis and an abnormal rise in ROS.
In the treatment phase, local p53 silencing consistently improved healing by more then a two fold (18 ± 2 days). VEGF production was significantly increased and pro-apoptotic factors were significantly downregulated in siRNA-treated Zmpste24-/- mice (p<0.05). DNA damage due to ROS production was also shown to be significantly decreased following treatment. Our results suggest a vasculogenic dysfunction in wound closure and showed that the specific knock down of p53 significantly improves WH.
Because EPCs showed impaired function, lower peripheric blood counts and impaired SDF-1α/HIF-1α signaling, we hypothesized that improving their mobilization by using a progenitor cell mobilizer, AMD3100, known to mobilize SCs from the BM, in a systemic treatment phase will improve WH. Peripheral blood counts were significantly increased and time to wound closure significantly decreased (20 days ± 2, p<0.05). Vasculogenic markers and anti- apoptotic molecules were upregulated compare to non-treated animals.
D. Conclusions
Obesity impaired wound closure is a complex problem with many contributory factors. Our results suggest that obesity impairs the BM-derived EPCs response to peripheral injury and this, in turn, impairs wound closure. This impairment is associated with decreased new blood vessel formation and increased DNA damage leading to an increase in the p53 pathway. We also demonstrate that targeted siRNA therapy can partially rescue impaired WH due to obesity. Based on these results we support the encouraging argument that, WH and closure has the potential be improved through specific local and systemic therapies in vivo in our rodent model and that further studies are needed to support this in a clinical environment.
Impaired WH due to ageing is a complex phenomenon that is partially understood. We demonstrate that the Zmpste24-/- transgenic knockout mouse provides a model for age-related WH investigation. Zmpste24-/- animals heals their wounds with significant delays, showed impaired EPCs mobilization following wounding through an impaired HIF-1α/SDF-1α pathway and increased apoptosis. Furthermore, WH can be improved through specific local siRNA therapy and systemic stem cell mobilization therapies.
Our results suggest strong similar patterns between obesity and ageing in the way they mediate WH impairments trough (premature) ageing. Our encouraging endeavor to bring WH back to baseline in these diseased models underlines the possibility to reverse the microenvironment alterations and improves EPCs contribution to the WH process. Because EPCs are involved in virtually every tissue repair process happening in the human body, we hope that this work will lead the way for new research in various fields in medicine to improve wound care and quality of life of patients.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
Atherton, Paul. "The role of ultrasound in wound healing". Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-ultrasound-in-wound-healing(94a0808e-f676-4431-a415-582525f24674).html.
Pełny tekst źródłaPugazhenthi, Kamali, i n/a. "Melatonin : a new factor in wound healing". University of Otago. Department of Pharmacology & Toxicology, 2008. http://adt.otago.ac.nz./public/adt-NZDU20081208.151313.
Pełny tekst źródłaTomás, Barberán Santiago. "Inflammation and wound healing following photorefractive keratectomy /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3449-5/.
Pełny tekst źródłaLai, Amy M. "Role of aminopeptidase N in wound healing". Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/39957.
Pełny tekst źródłaZhang, Gaofeng. "Electric signals regulated immunomodulation and wound healing". Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/42430/.
Pełny tekst źródłaSharma, G. U. "Modulation of wound healing after glaucoma surgery". Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1527404/.
Pełny tekst źródłaGreenhowe, Jennifer. "Stem and progenitor cells in wound healing". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:87a9a7a1-b595-458a-913f-64497174f988.
Pełny tekst źródłaCorbett, Laura. "Morphogen and epigenetic regulation of wound healing". Thesis, University of Newcastle upon Tyne, 2015. http://hdl.handle.net/10443/2935.
Pełny tekst źródłaWhitmont, Kaley J. "Activated protein C in cutaneous wound healing". Thesis, The University of Sydney, 2010. https://hdl.handle.net/2123/28899.
Pełny tekst źródłaBolitho, Christine. "Studies of serum albumin in wound healing and endothelial apoptosis". Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/4712.
Pełny tekst źródłaHsu, Chiao-Wen Ivy. "Serpina3n accelerates wound closure in a murine model of diabetic wound healing". Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50361.
Pełny tekst źródłaMedicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate
Boroumand, Soulmaz. "Investigating the epidermal Notch activation during wound healing and the consequences of prolonged Notch activity during skin wound healing". Thesis, Durham University, 2014. http://etheses.dur.ac.uk/10785/.
Pełny tekst źródłaHong, Sung-Ha. "Development of a wound dressing for detection of bacteria with wound healing properties". Thesis, University of Bath, 2013. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619143.
Pełny tekst źródłaKhathide, Bongai. "Assessing modified chitosan wound dressings to enhance wound healing in the porcine model". Thesis, University of Pretoria, 2020. http://hdl.handle.net/2263/75685.
Pełny tekst źródłaThesis (PhD)--University of Pretoria, 2020.
National Research Foundation of South Africa
Pharmacology
PhD (Pharmacology)
Unrestricted
Bohling, Mark W. "Cutaneous wound healing in the cat a macroscopic and histologic description and comparison with cutaneous wound healing in the dog /". Auburn, Ala., 2007. http://repo.lib.auburn.edu/2007%20Spring%20Dissertations/BOHLING_MARK_55.pdf.
Pełny tekst źródłaAdams, Titus Sam Turner. "Topical negative pressure therapy in wound healing : a research tool to study neutrophil-mediated wound pathophysiology in acute dermal wounds". Thesis, University of Bristol, 2003. http://hdl.handle.net/1983/02226e50-d53c-40e4-a38a-cede0dc8161f.
Pełny tekst źródłaKarlsson, Lena, i Susanne Asteberg. "Undertrycksbehandling hos diabetiker med fotsår". Thesis, Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-37785.
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