No / The hair follicle has an established role in wound re-epithelialisation, a phenomenon that has been appreciated since at least the first half of the last century. The bulge niche, one location of hair follicle epithelial stem cells has been of particular interest to researchers over recent years, with numerous studies showing its ability to directly contribute to epidermal repair. However, recent work has highlighted other progenitor regions of the hair follicle that appear to act as stem cells during epidermal repair. In addition, several studies within the last 12 months have questioned the importance of the bulge during re-epithelialisation, producing conflicting literature. Here we provide a new model to demonstrate how several important differences in experimental design between studies could account for these seemingly opposing findings, which may have implications for how future studies are conducted.

Yes / Purpose.: The aim of this work was to develop an in vitro cornea model to study the effect of proinflammatory cytokines on wound healing. Methods.: Initial studies investigated how to maintain the ex vivo models for up to 4 weeks without loss of epithelium. To study the effect of cytokines, corneas were cultured with the interleukins IL-17A, IL-22, or a combination of IL-17A and IL-22, or lipopolysaccharide (LPS). The effect of IL-17A on wound healing was then examined. Results.: With static culture conditions, organ cultures deteriorated within 2 weeks. With gentle rocking of media over the corneas and carbon dioxide perfusion, the ex vivo models survived for up to 4 weeks without loss of epithelium. The cytokine that caused the most damage to the cornea was IL-17A. Under static conditions, wound healing of the central corneal epithelium occurred within 9 days, but only a single-layered epithelium formed whether the cornea was exposed to IL-17A or not. With rocking of media gently over the corneas, a multilayered epithelium was achieved 9 days after wounding. In the presence of IL-17A, however, there was no wound healing evident. Characterization of the cells showed that wherever epithelium was present, both differentiated cells and highly proliferative cells were present. Conclusions.: We propose that introducing rocking to extend the effective working life of this model and the introduction of IL-17A to this model to induce aspects of inflammation extend its usefulness to study the effects of agents that influence corneal regeneration under normal and inflamed conditions.

The skin is a large organ consisting of different types of tissues. It serves many important functions such as protection against microorganisms, viruses, and harmful UV rays from the sun. Additionally, the skin plays a crucial role in regulating body temperature. It is composed of three layers: the epidermis, dermis, and subcutis. When injured, blood vessels in the dermis are penetrated, resulting in bleeding. Wound healing occurs through a process divided into four phases aimed at tissue repair. Honey has long been used for its health-promoting properties, especially in wound healing, although the molecular mechanisms underlying these properties remain unclear. To contribute to a better understanding of this, this literature review examines the effects of manuka honey on various types of wounds and aims to answer whether manuka honey works better compared to standard treatments for certain wound types. This work compiled results from randomized controlled trials retrieved from the PubMed database in 2024 using the search terms "manuka honey, wound healing." The five selected studies examined the effect of manuka honey on different types of wounds (diabetic foot ulcers, leg ulcers, wounds after tooth or nail extraction, and venous ulcers) compared to standard treatments such as dressings or placebos. The studies included participants from various countries and age groups. Exclusion criteria included age under 16 years, serious illnesses, honey allergies, and ongoing steroid or anti-inflammatory treatments. The results indicated that manuka honey improved healing time for certain wound types, such as neuropathic diabetic foot ulcers and post-tooth extraction wounds and contributed to changes in bacterial flora for venous leg ulcers. Despite these promising results, the studies showed no advantage of manuka honey dressings over paraffin dressings for postoperative and venous ulcers after longer treatment durations.

Wei, Fangyuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 182-211). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

HA (Hyaluronan, hyaluronic acid) is a predominant component of the extracellular matrix and plays diverse roles in the process of wound healing. The major significance of the biological functions of HA in wound healing arise from early studies showing that rich and prolonged existence of HA is associated with the fetal scarless wound healing. It has been hypothesized that adult wound healing can be modulated by the application of exogenous HA to make the process of wound repair more like regeneration. / In this thesis, the effects of molecular weight and concentration of HA on the biological behavior of human fibroblasts and keratinocytes have been investigated in both monolayer and 3D culture models. In addition, the mechanism for the HA-induced biological effects has also been investigated. Previous laboratory studies have primarily focused on individual cell type, but in wound healing in vivo there is considerable interaction between the keratinocytes and fibroblasts. The role of HA in keratinocyte-fibroblast interactions is not clear, so an organotypical culture model was used to investigate the keratinocyte differentiation and stratification and basement membrane formation with and without fibroblasts to explore the effect of HA on keratinocyte-fibroblast interactions. / The experimental data suggest that exogenous application of HA modulates the process of wound healing so that it becomes more like regeneration by regulating the biological functions of human keratinocytes and fibroblasts, including their interaction. By further understanding the HA-induced cell biological phenomena and involved mechanisms new approaches for wound care may be revealed. / The skin is the largest organ in the body. It consists of an outer layer, the epidermis supported by a connective tissue matrix, the dermis. The keratinocyte and fibroblast are the major cell types in the epidermis and dermis respectively. When the skin is damaged, the body will active a cascade of mechanisms to restore the tissue integrity. If the damaged tissue is limited to the epidermis, it will be restored by the process of regeneration. Regeneration involves the replacement of injured tissue by new tissue which has both form and function identical to the original tissue. If the defect involves the dermis, healing is achieved by repair which results in permanent scar formation. Wound healing is an extremely complex biological process which involves several overlapping steps; inflammation, granulation tissue formation and remodeling which are coordinated by various cell types, growth factors, cytokines and extracellular matrix components including hyaluronan. / Whilst there have been many studies looking at the effect of HA on different cell types using varying molecular parameters, concentrations and sources of HA, the result are often contradictory. Even the endogenous or exogenous application of HA have been reported to have opposite effects on cell behavior. / Gu, Hua. / Adviser: Andrew Bard. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0216. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 116-135). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Introduction: Endoscopic sinus surgery (ESS) is at present the gold standard therapeutic modality for chronic rhinosinusitis (CRS) resistant to medical therapy. Whilst results from ESS for CRS are generally good, postoperative bleeding and impaired wound healing with adhesion formation remains a concern. Due to patient discomfort and the detrimental effects on wound healing caused by most packing materials, many surgeons no longer routinely use nasal packing. Surgeons have in the past sought agents which would provide post-operative haemostasis without detrimentally affecting wound healing. Antifibrinolytics have been available for many years, however, their topical application has only been explored in the last few years. Recently different forms of chitosan have separately shown significant promise as powerful haemostatic and anti-adhesion agents. The aim of this thesis was to explore the progressive understanding of the interaction between haemostasis and wound healing with possible development of a novel agent. Methods: The first step to scientifically assess bleeding after sinus surgery was to develop a standardised method of video endoscopy and grading the surgical field during ESS. This was done as a multinational collaborative trial. Once this assessment tool was validated a randomised controlled trial evaluating the effect of two antifibrinolytics (epsilon aminocaproic acid and tranexamic acid) was conducted. Further evaluation was then conducted on other possible hemostatic and antiadhesion substances. This included various combinations of a novel chitosan gel. These gels were trialled in vitro to determine their effect on human nasal fibroblasts derived from CRS patients. Fibroblast adhesion and proliferation as well as closure of standardised wounds were studied. The most promising of these gels was then used in an in vivo sheep model. Once effectiveness of the chitosan-dextran gel was shown in the laboratory, this was evaluated against a number of currently available hemostatic and anti-adhesion substances in a standardised model of wound healing in sheep with CRS. This model had been previously extensively validated in our department. Full thickness mucosal injuries were created on the lateral nasal wall and ethmoids of twenty sheep and recombinant tissue factor (rTF), SprayGel or Chitosan-Dextran derivative gel applied topically in a randomized fashion. Adhesion formation and severity as well as microscopic wound healing and ciliary function were analysed at day 28, 56, 84 and 112 post initial surgery. A further sheep study was conducted applying chitosan dextran gel to standardised mucosal injuries and comparing its effect on the control of bleeding to control. Bleeding time and grade were recorded and wound healing monitored via serial videoendoscopy over two weeks and objectively measured. Results: a) Assessment of the bleeding scales showed that inter and intra observer reliability for both scales tested were significantly improved by employing a standardized video-endoscopy technique. The Wormald scale proved to be more reliable and sensitive to changes in the most common surgical fields encountered in ESS. b) Tranexamic acid showed a modest but clinically significant improvement in the surgical field at 2, 4 and 6 minutes after application. Epsilon aminocaproic acid did not effectively improve the surgical field. c) Nasal fibroblast adhesion and proliferation were significantly impaired with dextran and chitosan. The most effective ratio that delayed but did not prevent wound closure were 5 % chitosan: 5 % dextran gel. d) In a standardised sheep model of mucosal wound healing the chitosan gel significantly decreased lateral nasal wall and ethmoidal adhesions at all time points. The chitosan group had a significantly greater percentage of re-epithelialisation and reciliation than control and rTF. In addition the mean cilial grade in the chitosan group was significantly better than control. e) The chitosan dextran gel was significantly more haemostatic at 2,4, and 6 minutes after injury with no significant difference noted in wound healing. Conclusions: Standardised methods of videoendoscopy and grading the surgical field in ESS are valuable tools for further research. Tranexamic acid significantly improved the surgical field to a moderate degree in ESS compared to control. Chitosan gel is a promising new powerful haemostatic bio-polymer which has a mild inhibitory effect on fibroblast attachment and proliferation. This may partially explain the significant improvement in microscopic wound healing and reduction in adhesion formation seen in a sheep model of chronic sinusitis. Future work evaluating this gel in the setting of a human trial is currently underway. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1375402 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Embryonic stem cells (ESCs) can differentiate into all somatic cells, and as such, are a promising cell source for therapeutic applications. In vitro, ESCs spontaneously differentiate via the aggregation of cells into embryoid bodies (EBs), which recapitulate aspects of early embryogenesis and harbor a unique reservoir of cues critical for tissue formation and morphogenesis. Embryonic healing responses employ similar intrinsic machinery used for tissue development, and these morphogenic cues may be captured within the EB microenvironment. Recent studies have shown that when injected into injury or defect models in vivo, ESCs synthesize and secrete extracellular factors that ultimately contribute to repair, suggesting that these molecules may be as important for regenerative therapies as functional differentiation of the cells. The overall objective of this project was to develop novel acellular matrices derived from differentiating ESCs undergoing morphogenesis. The central hypothesis was that embryonic matrices contain complex mixtures of extracellular factors that, when isolated, retain bioactivity and enhance wound healing in an adult environment. The overall objective was accomplished by: (1) investigating the production of extracellular matrix (ECM) by differentiating ESCs as a function of differentiation time; (2) assessing the ability of solvents to efficiently decellularize EBs; and (3) evaluating the healing response elicited by acellular matrices derived from EBs in a murine dermal wound healing model. Endogenous ECM synthesis by EBs varied with time and was associated with specific differentiation events. Novel techniques were developed to effectively remove cell components from EBs in order to extract complex, bioactive acellular matrices. EB-derived acellular matrices significantly enhanced the healing of excisional dermal wounds in mice, indicating the potency of extracellular factors synthesized by ESCs. All together, these studies demonstrate that acellular matrices derived from ESCs retain morphogenic factors capable of influencing tissue repair. In addition, this work lays the foundation for future studies to further examine the functional role of endogenous matrix molecules on ESC differentiation and to evaluate the utility of a stem cell-derived matrix for a variety of regenerative medicine applications.

Introduction: Endoscopic sinus surgery (ESS) is at present the gold standard therapeutic modality for chronic rhinosinusitis (CRS) resistant to medical therapy. Whilst results from ESS for CRS are generally good, postoperative bleeding and impaired wound healing with adhesion formation remains a concern. Due to patient discomfort and the detrimental effects on wound healing caused by most packing materials, many surgeons no longer routinely use nasal packing. Surgeons have in the past sought agents which would provide post-operative haemostasis without detrimentally affecting wound healing. Antifibrinolytics have been available for many years, however, their topical application has only been explored in the last few years. Recently different forms of chitosan have separately shown significant promise as powerful haemostatic and anti-adhesion agents. The aim of this thesis was to explore the progressive understanding of the interaction between haemostasis and wound healing with possible development of a novel agent. Methods: The first step to scientifically assess bleeding after sinus surgery was to develop a standardised method of video endoscopy and grading the surgical field during ESS. This was done as a multinational collaborative trial. Once this assessment tool was validated a randomised controlled trial evaluating the effect of two antifibrinolytics (epsilon aminocaproic acid and tranexamic acid) was conducted. Further evaluation was then conducted on other possible hemostatic and antiadhesion substances. This included various combinations of a novel chitosan gel. These gels were trialled in vitro to determine their effect on human nasal fibroblasts derived from CRS patients. Fibroblast adhesion and proliferation as well as closure of standardised wounds were studied. The most promising of these gels was then used in an in vivo sheep model. Once effectiveness of the chitosan-dextran gel was shown in the laboratory, this was evaluated against a number of currently available hemostatic and anti-adhesion substances in a standardised model of wound healing in sheep with CRS. This model had been previously extensively validated in our department. Full thickness mucosal injuries were created on the lateral nasal wall and ethmoids of twenty sheep and recombinant tissue factor (rTF), SprayGel or Chitosan-Dextran derivative gel applied topically in a randomized fashion. Adhesion formation and severity as well as microscopic wound healing and ciliary function were analysed at day 28, 56, 84 and 112 post initial surgery. A further sheep study was conducted applying chitosan dextran gel to standardised mucosal injuries and comparing its effect on the control of bleeding to control. Bleeding time and grade were recorded and wound healing monitored via serial videoendoscopy over two weeks and objectively measured. Results: a) Assessment of the bleeding scales showed that inter and intra observer reliability for both scales tested were significantly improved by employing a standardized video-endoscopy technique. The Wormald scale proved to be more reliable and sensitive to changes in the most common surgical fields encountered in ESS. b) Tranexamic acid showed a modest but clinically significant improvement in the surgical field at 2, 4 and 6 minutes after application. Epsilon aminocaproic acid did not effectively improve the surgical field. c) Nasal fibroblast adhesion and proliferation were significantly impaired with dextran and chitosan. The most effective ratio that delayed but did not prevent wound closure were 5 % chitosan: 5 % dextran gel. d) In a standardised sheep model of mucosal wound healing the chitosan gel significantly decreased lateral nasal wall and ethmoidal adhesions at all time points. The chitosan group had a significantly greater percentage of re-epithelialisation and reciliation than control and rTF. In addition the mean cilial grade in the chitosan group was significantly better than control. e) The chitosan dextran gel was significantly more haemostatic at 2,4, and 6 minutes after injury with no significant difference noted in wound healing. Conclusions: Standardised methods of videoendoscopy and grading the surgical field in ESS are valuable tools for further research. Tranexamic acid significantly improved the surgical field to a moderate degree in ESS compared to control. Chitosan gel is a promising new powerful haemostatic bio-polymer which has a mild inhibitory effect on fibroblast attachment and proliferation. This may partially explain the significant improvement in microscopic wound healing and reduction in adhesion formation seen in a sheep model of chronic sinusitis. Future work evaluating this gel in the setting of a human trial is currently underway. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1375402 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 223-247).

Os retalhos cutâneos são amplamente utilizados na cirurgia plástica, principalmente na reparadora. Após o procedimento operatório, uma das principais complicações é a isquemia, podendo ocasionar a necrose do retalho. Vários recursos têm sido estudados com o intuito de aumentar a viabilidade desses retalhos. Dentre esses recursos, o laser de baixa intensidade é uma alternativa de tratamento, uma vez que pode promover um aumento da microcirculação e da neoformação vascular. Entretanto, existem discrepâncias na literatura em relação aos parâmetros empregados no uso do laser de baixa intensidade, principalmente das fluências utilizadas nos tratamentos. Este estudo teve como objetivo verificar o efeito de diferentes fluências do laser de 670nm, na viabilidade do retalho cutâneo randômico em ratos. Foram utilizados 100 ratos, da linhagem Wistar, distribuídos em 5 grupos de 20 animais cada. O retalho cutâneo randômico de base cranial foi realizado com dimensões de 10 X 4 cm e uma barreira plástica foi interposta entre o mesmo e o leito doador. O grupo 1 (controle) foi submetido à simulação de tratamento com o aparelho desligado. O grupo 2 foi submetido à radiação laser com fluência de 3 J/\'CM POT.2\'. Os grupos 3, 4 e 5 foram irradiados com fluências de 6 J/\'CM POT.2\', 12 J/\'CM POT.2\' e 24 J/\'CM POT.2\', respectivamente. Todos os grupos experimentais receberam a radiação laser imediatamente após o procedimento operatório e nos 4 dias subseqüentes, utilizando-se a técnica pontual em contato em 24 pontos distribuídos sobre e ao redor do retalho. No sétimo dia pós-operatório, as porcentagens da área de necrose dos retalhos foram avaliadas pelo método do gabarito de papel e também foi coletada uma amostra do retalho de 10 animais de cada grupo, escolhidos aleatoriamente, para a realização da contagem dos vasos sangüíneos. O grupo 1 apresentou média de área de necrose de 49,92%; o grupo 2 - 41,84%; o grupo 3 - 36,51%; o grupo 4 - 29,45% e o grupo 5 - 20,37%. Na contagem dos vasos, o grupo 1 obteve média de 65,2; o grupo 2 - 92,6; o grupo 3 - 105,5; o grupo 4 - 128,7 e o grupo 5 - 171,0. Na análise estatística, realizou-se a ANOVA, seguida do teste de comparações múltiplas de Tukey. Os resultados mostraram que todos os grupos experimentais apresentaram valores estatisticamente significativos comparados ao grupo controle, sendo que o grupo 5 apresentou a menor área de necrose e o maior número de vasos quando comparado aos demais grupos deste estudo (p < 0,01). O teste de correlação linear de Pearson indicou alta correlação negativa entre a porcentagem de necrose e o número de vasos dos retalhos (-0,972 / p = 0,0001). O laser de baixa intensidade (670nm) aplicado com fluência de 24 J/\'CM POT.2\' foi mais eficaz no aumento da viabilidade do retalho cutâneo randômico em ratos, comparado às outras fluências utilizadas neste estudo. / Skin flaps are widely used in plastic surgery, mainly in repair surgeries. After this reconstructive procedure, one of the main consequences is the decrease of blood flow in the area, which can be responsible by tissue necrosis. In this context, a lot of studies have investigated treatments able to increase the viability of the flap and the low level laser therapy (LLLT) has been chosen as an efficient treatment to reduce post-injury inflammatory processes and to stimulate the formation of new blood vessels. However, the use of a wide range of fluences by different authors and the lack of standardized experimental conditions make it difficult to compare published results. The aim of this study was to investigate the dose-response effects of 670nm laser on the viability of random skin flap in rats. One hundred Wistar male rats were used in this study. The animals were divided into 5 groups: group 1 (control group); group 2 (treated with 3 J/\'CM POT.2\'); group 3 (treated with 6 J/\'CM POT.2\'); group 4 (treated with 12 J/\'CM POT.2\') and group 5 (treated with 24 J/\'CM POT.2\'). The skin flap was made on the back of all animals studied (dimensions: 10 x 4 cm) and before the sutures were done, a plastic sheet was interposed between the flap and the donor site. Laser irradiation was performed immediately after the surgery and on days 1, 2, 3 and 4 post-surgery. The irradiation was made punctually, on 24 points on the skin surface and around it. The percentage of the necrosis area of the flap was calculated by the paper template method at the day 7 postoperative. Moreover, a sample of the skin flaps was collected from 10 rats of each group, which were chosen aleatory, to performe the count of the blood vessels. The animals of all treated groups showed statistically significant differences when compared to the control group (necrosis area: 49, 92%). The necrosis area of the treated groups were 41,82% (group 2), 36,51% (group 3), 29,45% (group 4) and 20,37% (group 5). In the count of blood vessels, group 1 showed the mean of 65,2; group 2 - 92,6; group 3 - 105,5; group 4 - 128,7 and group 5 - 171,0. The ANOVA test, followed by the Tukey test, for multiple comparasions were used. The results showed that all experimental groups showed statistically lower values for the necrosis area compared to the control and a higher number of blood vessels in the skin flap. It can be observed that the best results were found in the animals of group 5 (p < 0,01). In addition, the Pearson coefficient showed a significant negative correlation between necrosis area and the number of vessels (-0,972 / p = 0,0001). This present study has demonstrated that the 670nm laser was efficient to increase the viability of the skin flap, at all fluences used, with a tendency of reaching better results at higher dosages (24 J/\'CM POT.2\').