Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 156
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nat Immunol ; 23(4): 518-531, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35354953

RESUMO

Internal organs heal injuries with new connective tissue, but the cellular and molecular events of this process remain obscure. By tagging extracellular matrix around the mesothelium lining in mouse peritoneum, liver and cecum, here we show that preexisting matrix was transferred across organs into wounds in various injury models. Using proteomics, genetic lineage-tracing and selective injury in juxtaposed organs, we found that the tissue of origin for the transferred matrix likely dictated the scarring or regeneration of the healing tissue. Single-cell RNA sequencing and genetic and chemical screens indicated that the preexisting matrix was transferred by neutrophils dependent on the HSF-integrin AM/B2-kindlin3 cascade. Pharmacologic inhibition of this axis prevented matrix transfer and the formation of peritoneal adhesions. Matrix transfer was thus an early event of wound repair and provides a therapeutic window to dampen scaring across a range of conditions.


Assuntos
Neutrófilos , Peritônio , Animais , Epitélio , Matriz Extracelular , Camundongos , Peritônio/lesões , Cicatrização
2.
Nature ; 623(7988): 792-802, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37968392

RESUMO

Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation1. Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics and genetic lineage tracing, ablation and gene deletion models, we demonstrate that CD201+ progenitors control the pace of wound healing by generating multiple specialized cell types, from proinflammatory fibroblasts to myofibroblasts, in a spatiotemporally tuned sequence. We identified retinoic acid and hypoxia signalling as the entry checkpoints into proinflammatory and myofibroblast states. Modulating CD201+ progenitor differentiation impaired the spatiotemporal appearances of fibroblasts and chronically delayed wound healing. The discovery of proinflammatory and myofibroblast progenitors and their differentiation pathways provide a new roadmap to understand and clinically treat impaired wound healing.


Assuntos
Receptor de Proteína C Endotelial , Fáscia , Cicatrização , Animais , Camundongos , Diferenciação Celular , Hipóxia Celular , Linhagem da Célula , Modelos Animais de Doenças , Receptor de Proteína C Endotelial/metabolismo , Fáscia/citologia , Fáscia/lesões , Fáscia/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Inflamação/metabolismo , Inflamação/patologia , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Transdução de Sinais , Análise da Expressão Gênica de Célula Única , Pele/citologia , Pele/lesões , Pele/metabolismo , Tretinoína/metabolismo
4.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256251

RESUMO

The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such as mechanical stress, osmotic pressure, and temperature. TRPV4 enables the entry of cation ions, particularly calcium ions, into the cell. Activation of TRPV4 channels initiates calcium oscillations, which trigger intracellular signaling pathways involved in a plethora of cellular processes, including tissue repair. Widely expressed throughout the body, TRPV4 can be activated by a wide array of physicochemical stimuli, thus contributing to sensory and physiological functions in multiple organs. This review focuses on how TRPV4 senses environmental cues and thereby initiates and maintains calcium oscillations, critical for responses to organ injury, tissue repair, and fibrosis. We provide a summary of TRPV4-induced calcium oscillations in distinct organ systems, along with the upstream and downstream signaling pathways involved. In addition, we delineate current animal and disease models supporting TRPV4 research and shed light on potential therapeutic targets for modulating TRPV4-induced calcium oscillation to promote tissue repair while reducing tissue fibrosis.


Assuntos
Antineoplásicos , Sinalização do Cálcio , Animais , Canais de Cátion TRPV , Cicatrização , Fibrose , Íons
5.
Int J Mol Sci ; 25(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38791352

RESUMO

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.


Assuntos
Regeneração Óssea , Fêmur , Fibrina , Animais , Regeneração Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fibrina/metabolismo , Embrião de Galinha , Densidade Óssea/efeitos dos fármacos , Hidrogéis , Microtomografia por Raio-X , Engenharia Tecidual/métodos , Soro/metabolismo , Soro/química
6.
J Reconstr Microsurg ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38272059

RESUMO

BACKGROUND: Knowledge of tissue and implant density is crucial in obtaining both volume and weight symmetry in unilateral breast reconstruction. Therefore, the aim of this study was to determine and compare the density of abdominal and breast tissue specimens as well as of 5th generation breast implants. METHODS: Thirty-one breast tissue and 30 abdominal tissue specimens from 61 patients undergoing either mammaplasty or abdominoplasty as well as five different 5th generation breast implants were examined. Density (g/mL) was calculated by applying the water displacement method. RESULTS: The mean specimen density was 0.94 ± 0.02 g/mL for breast tissue and 0.94 ± 0.02 g/mL for abdominal tissue, showing no significant difference (p = 0.230). Breast tissue density significantly (p = 0.04) decreased with age, while abdominal tissue did not. A regression equation to calculate the density of breast tissue corrected for age (breast density [g/mL] = 0.975-0.0007 * age) is provided. Breast tissue density was not related to body mass index, past pregnancy, or a history of breastfeeding. The breast implants had a density ranging from 0.76 to 1.03 g/mL which differed significantly from breast tissue density (-0.19 g/mL [-19.8%] to +0.09 g/mL [+9.58%]; p ≤ 0.001). CONCLUSION: Our results support the suitability of abdominal-based perforator flaps in achieving both volume and weight symmetry in unilateral autologous breast reconstruction. Abdominal flap volume can be derived one-to-one from mastectomy weight. Further, given significant brand-dependent density differences, the potential to impose weight disbalances when performing unilateral implant-based reconstructions of large breasts should be considered.

7.
J Craniofac Surg ; 34(3): 888-892, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36397205

RESUMO

BACKGROUND: Our previous retrospective study indicates that esthetic surgery in general results in a significant improvement in Quality of life (QoL). This is the first indication-specific prospective evaluation of QoL after blepharoplasty using standardized and validated questionnaires. OBJECTIVES: To report changes in QoL after blepharoplasty prospectively with a 6-month follow-up. METHODS: The same surgical team performed an esthetic blepharoplasty on 50 patients. Participants answered 1 set of questionnaires preoperatively and 6 months postoperatively. The instrument consisted of a self-developed indication-specific part specially designed for blepharoplasty and 4 validated and standardized testing instruments (FLZ, FPI-R, RSES, and PHQ-4) with norm data for German-speaking countries available. RESULTS: This study reveals a high rate of satisfaction after blepharoplasty. 96% felt better about themselves and 94% would undergo the procedure again. Statistically significant increased values were found postoperatively in the items "income" ( P =0.016), "family life" ( P =0.028), "partner relationship" ( P =0.039), "ability to relax" ( P <0.001), "energy" ( P <0.001), "hobbies" ( P <0.001), and with their outer appearance in general ( P =0.018). Blepharoplasty showed a statistically significant improvement in emotional stability ( P =0.017) and a reduction in depressive symptoms ( P <0.001). Our patients had statistically significantly higher self-esteem before ( P <0.001) and after ( P <0.001) the intervention. CONCLUSION: Our prospective study shows that blepharoplasty increases most aspects of QoL significantly, has a positive effect on emotional and physical well-being, and reduces the incidence of depressive symptoms and anxiety.


Assuntos
Blefaroplastia , Humanos , Blefaroplastia/métodos , Estudos Prospectivos , Qualidade de Vida/psicologia , Satisfação do Paciente , Estética Dentária , Inquéritos e Questionários
8.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36768283

RESUMO

Strategies for therapeutic lymphangiogenesis are gradually directed toward the use of growth factor preparations. In particular, blood-derived growth factor products, including Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP), are both clinically employed for accelerating tissue repair and have received considerable attention in the field of regenerative medicine research. In this study, a comparative analysis of HPS and PRP was conducted to explore their lymphangiogenic potential. We found higher pro-lymphangiogenic growth factor concentrations of VEGF-C, PDGF-BB, and bFGF in HPS in comparison to normal serum (NS) and PRP. The proliferation and migration of lymphatic endothelial cells (LECs) were promoted considerably with both HPS and PRP, but the strongest effect was achieved with HPS-40% dilution. Tube formation of LECs showed the highest number of tubes, branching points, greater tube length, and cell-covered area with HPS-10%. Finally, the effects were double-validated using an ex vivo lymphatic ring assay, in which the highest number of sprouts and the greatest sprout length were achieved with HPS-10%. Our findings demonstrate the superior lymphangiogenic potential of a new generation blood-derived secretome obtained by hypoxic preconditioning of peripheral blood cells-a method that offers a novel alternative to PRP.


Assuntos
Células Endoteliais , Peptídeos e Proteínas de Sinalização Intercelular , Linfangiogênese , Plasma Rico em Plaquetas , Soro , Cicatrização , Células Endoteliais/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfangiogênese/fisiologia , Plasma Rico em Plaquetas/química , Plasma Rico em Plaquetas/metabolismo , Precondicionamento Isquêmico , Soro/química , Soro/metabolismo , Cicatrização/fisiologia
9.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982558

RESUMO

Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are regenerative blood-derived growth factor compositions that have been extensively examined for their angiogenic and lymphangiogenic activity towards wound healing and tissue repair. Optimization of these secretomes' growth factor profile, through adjustments of the conditioning parameters, is a key step towards clinical application. In this study, the autologous liquid components (plasma/serum) of HPP and HPS were replaced with various conditioning media (NaCl, PBS, Glucose 5%, AIM V medium) and were analyzed in terms of key pro- (VEGF-A, EGF) and anti-angiogenic (TSP-1, PF-4) protein factors, as well as their ability to promote microvessel formation in vitro. We found that media substitution resulted in changes in the concentration of the aforementioned growth factors, and also influenced their ability to induce angiogenesis. While NaCl and PBS led to a lower concentration of all growth factors examined, and consequently an inferior tube formation response, replacement with Glucose 5% resulted in increased growth factor concentrations in anticoagulated blood-derived secretomes, likely due to stimulation of platelet factor release. Medium substitution with Glucose 5% and specialized peripheral blood cell-culture AIM V medium generated comparable tube formation to HPP and HPS controls. Altogether, our data suggest that medium replacement of plasma and serum may significantly influence the growth factor profile of hypoxia-preconditioned blood-derived secretomes and, therefore, their potential application as tools for promoting therapeutic angiogenesis.


Assuntos
Secretoma , Cloreto de Sódio , Humanos , Meios de Cultivo Condicionados/farmacologia , Hipóxia Celular , Neovascularização Fisiológica , Hipóxia , Peptídeos e Proteínas de Sinalização Intercelular
10.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445617

RESUMO

Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage defects remains challenging in terms of maintaining chondrogenic phenotype during in vitro chondrocyte expansion. Growth factor supplementation has been found supportive in improving ACI outcomes by promoting chondrocyte redifferentiation. Here, we analysed the chondrogenic growth factor concentrations in the human blood-derived secretome of Hypoxia Preconditioned Serum (HPS) and assessed the effect of HPS-10% and HPS-40% on human articular chondrocytes from osteoarthritic cartilage at different time points compared to normal fresh serum (NS-10% and NS-40%) and FCS-10% culture conditions. In HPS, the concentrations of TGF-beta1, IGF-1, bFGF, PDGF-BB and G-CSF were found to be higher than in NS. Chondrocyte proliferation was promoted with higher doses of HPS (HPS-40% vs. HPS-10%) and longer stimulation (4 vs. 2 days) compared to FCS-10%. On day 4, immunostaining of the HPS-10%-treated chondrocytes showed increased levels of collagen type II compared to the other conditions. The promotion of the chondrogenic phenotype was validated with quantitative real-time PCR for the expression of collagen type II (COL2A1), collagen type I (COL1A1), SOX9 and matrix metalloproteinase 13 (MMP13). We demonstrated the highest differentiation index (COL2A1/COL1A1) in HPS-10%-treated chondrocytes on day 4. In parallel, the expression of differentiation marker SOX9 was elevated on day 4, with HPS-10% higher than NS-10/40% and FCS-10%. The expression of the cartilage remodelling marker MMP13 was comparable across all culture conditions. These findings implicate the potential of HPS-10% to improve conventional FCS-based ACI culture protocols by promoting the proliferation and chondrogenic phenotype of chondrocytes during in vitro expansion.


Assuntos
Cartilagem Articular , Condrócitos , Humanos , Cartilagem Articular/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Matriz Extracelular/metabolismo , Hipóxia/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Fenótipo
11.
J Reconstr Microsurg ; 39(5): 367-373, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36075381

RESUMO

BACKGROUND: Defects at the forefoot frequently require microsurgical reconstruction; however, reconstructive failure can lead to results inferior to primary amputation. The purpose of this study was to identify independent factors affecting surgical outcomes and hospitalization time in these patients. METHODS: All patients that underwent free flap reconstruction of the forefoot between 2008 and 2019 were reviewed retrospectively. Statistical evaluation included binary logistic regression and correlation analysis. RESULTS: A total of 93 free flap procedures were performed in 87 patients. The most common defect etiologies were acute trauma (30 cases; 32.3%), diabetic foot syndrome (20 cases; 21.5%), and infection (17 cases; 18.3%). Muscle flaps were used in 50 cases (53.8%) and fasciocutaneous flaps were used in 43 cases (46.2%). Major complications occurred in 24 cases (25.8%) including 11 total flap losses and 2 partial flap losses. Minor complications occurred in 38 cases (40.9%). Patients aged 60 years or above were at significant higher risk of major complications (p = 0.029). Use of fasciocutaneous flaps (odds ratio [OR]: 14.341; p = 0.005), arterial hypertension (OR: 18.801; p = 0.014), and operative time (min) (OR: 1.010; p = 0.029) were identified as individual risk factors for major complications. Two venous anastomoses significantly reduced the risk of major complications (OR: 0.078; p = 0.022). Multiresistant bacterial wound colonization (OR: 65.152; p < 0.001) and defect size (OR: 1.007; p = 0.045) were identified as independent risk factors for minor complications. The median hospital stay was 28 days (7-85 days). Age significantly correlated with the length of hospital stay (r = 0.405, p < 0.01). CONCLUSION: Our study identified independent risk factors that might help to make individual decisions whether to target microsurgical forefoot reconstruction or primary amputation. Two venous anastomoses should be performed whenever feasible, and muscle free flaps should be preferred in patients at higher risk of major surgical complications.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias
12.
J Cell Mol Med ; 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145735

RESUMO

As one of the most common pathological processes in the clinic, wound healing has always been an important topic in medical research. Improving the wound healing environment, shortening the healing time and promoting fast and effective wound healing are hot and challenging issues in clinical practice. The nuclear factor-erythroid-related factor 2 (NFE2L2 or NRF2) signalling pathway reduces oxidative damage and participates in the regulation of anti-oxidative gene expression in the process of oxidative stress and thus improves the cell protection. Activation of the NRF2 signalling pathway increases the resistance of the cell to chemical carcinogens and inflammation. The signal transduction pathway regulates anti-inflammatory and antioxidant effects by regulating calcium ions, mitochondrial oxidative stress, autophagy, ferroptosis, pyroptosis and apoptosis. In this article, the role of the NRF2 signalling pathway in wound healing and its research progress in recent years are reviewed. In short, the NRF2 signalling pathway has crucial clinical significance in wound healing and is worthy of further study.

13.
Ann Plast Surg ; 87(1): 91-97, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661220

RESUMO

BACKGROUND: Partly as a result of the increasing attention directed toward transgender individuals and despite much research work on the topic of quality of life (QOL) of transgender, there is still a lack of studies using standardized questionnaires in their evaluation. AIMS: We designed a survey to evaluate the influence of surgery after phalloplasty (osteofasciocutaneous fibula free flap or osteofasciocutaneous radial free forearm flap) on QOL, emotional stability, self-esteem, and psyche of postoperated transgender men. METHODS: The present study included 32 transgender men who had undergone gender-affirming surgery (GAS) exclusively in our department between 2000 and 2012. Apart from our self-developed, indication-specific questionnaire with questions on socioeconomic and demographic data as well as postoperative satisfaction, the testing instrument included 4 frequently used, standardized testing instruments, which we compared with normative data. These included (a) a self-assessment test Fragebogen zur Lebenszufriedenheit with questions on QOL consisting of 3 modules (general satisfaction, satisfaction with health, and satisfaction with body image/outer appearance), (b) the Freiburg Personality Inventory, (c) the Rosenberg Self-Esteem Questionnaire, and (d) the Patient Health Questionnaire 4. FINDINGS: Our self-developed, indication-specific questionnaire showed that 88% of our patients were very satisfied with the aesthetic result, 75% have had sex after surgery, and 72% were very satisfied with sexual function after GAS. Eighty-one percent had a strong improvement of QOL, and 91% would undergo the same treatment again. Eighty-four percent would recommend GAS to others. All patients lived as men fulltime. DISCUSSION: Our study reveals that GAS plays an important part in the interdisciplinary treatment of transgender individuals as it improves the QOL in transgender men in most aspects of everyday life and has a positive influence on the patients' psyche and self-esteem in a retrospective study.


Assuntos
Pessoas Transgênero , Transexualidade , Humanos , Masculino , Satisfação do Paciente , Satisfação Pessoal , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários , Transexualidade/cirurgia
14.
J Wound Care ; 30(8): 604-611, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34382852

RESUMO

OBJECTIVE: To clarify the role of microbiological swabs in surgical decision-making, we investigated the effect of negative-pressure wound therapy (NPWT) and serial surgical debridement on bacterial bioburden in hard-to-heal wounds and ultimately correlated them with the success of surgical closure. METHOD: All patients were treated with surgical debridement, jet lavage and NPWT before their wounds were finally closed. The treatment effect was assessed by correlating microbiological swabs obtained immediately after intervention with those obtained after removal of the dressings during the following surgical procedures. The result of the last microbiological swab taken before definitive surgical closure was correlated with the requirement for revision surgery. RESULTS: We included the results of 704 microbiological swabs from 97 patients in 110 wound localisations in this monocentric, retrospective study. NPWT did not improve bacterial bioburden in 77% of cases and the duration of NPWT did not affect the result. Furthermore, no significant effect of NPWT could be found for either anaerobic (p=0.96) or aerobic bacteria (p=0.43). In contrast, surgical debridement decreased bacterial load in approximately 60% of cases. If sterile wound swabs could be obtained at all, it was during the first four surgical debridements in 60% of patients; after that only 10% became sterile. CONCLUSIONS: Sterile microbiological wound swabs before surgical closure were associated with lower rates of revision surgery, while low or medium bacterial loads did not increase revision rates.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Bandagens , Desbridamento , Humanos , Estudos Retrospectivos , Cicatrização
15.
Facial Plast Surg ; 37(5): 639-645, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33706388

RESUMO

As our previous studies have shown, cosmetic surgery has a positive correlation with postoperative well-being. The aim of this study was to prospectively examine the postoperative changes in quality of life (QoL) after a rhinoplasty. Thirty-four patients who underwent septorhinoplasty performed by a single surgeon from July 2015 to October 2018 reported in indication-specific self-developed and different validated questionnaires (FLZM or Fragen zur Lebenszufriedenheit Module, Freiburg Personality Inventor, Rosenberg self-esteem scale, Functional Rhinoplasty Outcome Inventory 17 [FROI-17], and Glasgow Benefit Inventory [GBI]) on the status of their QoL preoperatively (T0) and 6 months' follow-up (T1). Our goal was to assess the difference in psyche and self-esteem and to get objective insights into the effect of the operation. Significant improvements in QoL in terms of general module, health, and appearance were noted. The general part of the FLZM showed increasing T1 values in the sum scores (p = 0.005). With regard to the item "health," T1 was better than the norm data (p = 0.003). The statistically significant improvement for the item nose appearance (p < 0.0001) after operation and T1 versus reference data (p < 0.010) should be highlighted. The subjective patient ratings showed statistically significant T1 improvements for all items of the FROI-17: overall nose (p < 0.0001), nasal function (p = 0.001), general/further symptoms (p = 0.006), and confidence increased by aesthetic changes (p < 0.0001). Furthermore, the GBI score shows an improved QoL after rhinoplasty (p < 0.0001). Based on the assessment of a variety of disease- and nondisease-specific validated questionnaires, numerous improvements in the QoL of the patients were observed. Therefore, we support septorhinoplasty as a meaningful procedure regarding QoL improvement. The level of evidence is Level II prospective cohort study.


Assuntos
Qualidade de Vida , Rinoplastia , Humanos , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
16.
J Tissue Viability ; 30(3): 446-453, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33707159

RESUMO

INTRODUCTION: Metabolic diseases like diabetes mellitus often show prolonged healing and chronic wounds. Occlusive wound dressings are known to support wound closure by creating a moist environment which supports collagen synthesis, epithelialization and angiogenesis. We aimed to assess the effect of occlusion on diabetic wound fluid on the cellular level regarding fibroblast activity and angiogenetic response. MATERIAL AND METHODS: 22 split skin donor sites from 22 patients (11 patients with diabetes mellitus) were treated with occlusive dressings intraoperatively. On day 3, fluid and blood serum samples were harvested while changing the dressings. The influence of wound fluid on fibroblasts was assessed by measuring metabolic activity (Alamar Blue assay, Casey Counter), cell stress/death (LDH assay) and migration (in vitro wound healing assay) of fibroblasts. Angiogenesis of endothelial cells (HUVEC) was analyzed with the tube formation assay. Furthermore, a Magnetic Luminex Assay for multi-cytokines detection was performed focusing on inflammatory and pro-angiogenetic cytokines. RESULTS: The influence of wound fluid under occlusive dressings from diabetic patients showed a significantly increased angiogenic response and fibroblast migration compared to the non-diabetic patient group. Additionally, cell stress was increased in the diabetic group. Cytokine analysis showed an increase in VEGF-A in the diabetic group. CONCLUSION: Occlusive dressings may stimulate regenerative effects in diabetic wounds. Our in-vitro study shows the influence of wound fluid under occlusive dressings from diabetic patients on angiogenesis, migration and proliferation of fibroblasts, which are essential modulators of wound healing and scar modulation.


Assuntos
Indutores da Angiogênese , Complicações do Diabetes/prevenção & controle , Fibroblastos/fisiologia , Ferimentos e Lesões/terapia , Contagem de Células/métodos , Contagem de Células/estatística & dados numéricos , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/fisiopatologia , Fibroblastos/metabolismo , Humanos , Curativos Oclusivos/efeitos adversos , Curativos Oclusivos/estatística & dados numéricos , Ferimentos e Lesões/fisiopatologia
17.
Appl Microbiol Biotechnol ; 104(2): 725-739, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31822980

RESUMO

The recent use of photosynthetic organisms such as Chlamydomonas reinhardtii in biomedical applications has demonstrated their potential for the treatment of acute and chronic tissue hypoxia. Moreover, transgenic microalgae have been suggested as an alternative in situ drug delivery system. In this study, we set out to identify the best available combination of strains and expression vectors to establish a robust platform for the expression of human pro-angiogenic growth factors, i.e., hVEGF-165, hPDGF-B, and hSDF-1, in biomedical settings. As a case study, combinations of two expression vectors (pOpt and pBC1) and two C. reinhardtii strains (UVM4 and UVM11) were compared with respect to hVEGF-165 transgene expression by determination of steady-state levels of transgenic transcripts and immunological detection of recombinant proteins produced and secreted by the generated strains. The results revealed the combination of the UVM11 strain with the pBC1 vector to be the most efficient one for high-level hVEGF-165 production. To assess the robustness of this finding, the selected combination was used to create hPDGF-B and hSDF-1 transgenic strains for optimized recombinant protein expression. Furthermore, biological activity and functionality of algal-produced recombinant pro-angiogenic growth factors were assessed by receptor phosphorylation and in vitro angiogenesis assays. The results obtained revealed a potentiating effect in the combinatorial application of transgenic strains expressing either of the three growth factors on endothelial cell tube formation ability, and thus support the idea of using transgenic algae expressing pro-angiogenic growth factors in wound healing approaches.


Assuntos
Quimiocina CXCL12/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Proteínas Recombinantes/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Indutores da Angiogênese , Quimiocina CXCL12/genética , Células Endoteliais/efeitos dos fármacos , Expressão Gênica , Perfilação da Expressão Gênica , Vetores Genéticos , Proteoma/análise , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Recombinantes/genética , Transcrição Gênica , Fator A de Crescimento do Endotélio Vascular/genética
18.
Ann Plast Surg ; 85(5): 539-545, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32079811

RESUMO

INTRODUCTION: Periprosthetic joint infection (PJI) is a severe complication after a total knee replacement that is primarily associated with soft tissue defects. Finding an appropriate therapy for PJI is a major challenge because of the lack of guidelines and research comparing treatment options. METHODS: In this study, we retrospectively compared 78 patients who had a knee prosthetic infection within a mean follow-up period of 24 months. Group A received a soft tissue coverage in addition to orthopedic surgical therapy with or without a component replacement (CR) of the prosthesis. Group B received the same orthopedic treatment without plastic surgery for soft tissue coverage. RESULTS: Only 21% of the patients in group A received a CR compared with 70% in group B (P = 0.0001). In group A, 83% did not have a recurrent infection, and in group B, 57% of the patients had no further infection and regained joint function (P = 0.0376). In group A, only 15% of the patients who received a CR had a significant complication within the follow-up period of 2 years, whereas in group B, 75% of patients exhibiting a major complication (P = 0.0048*). CONCLUSIONS: Soft tissue coverage improves the outcome after PJI of the knee with soft tissue defects. Patients who simultaneously needed plastic surgery for defect coverage and orthopedic surgery for CR had the lowest number of complications overall. Based on the results of this study, a therapy algorithm could be identified considering the soft tissue defect grade leading to the lowest major complication rates and maximizing the outcome of knee prosthesis infection therapies.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Procedimentos de Cirurgia Plástica , Infecções Relacionadas à Prótese , Artroplastia do Joelho/efeitos adversos , Humanos , Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos
19.
Aesthet Surg J ; 40(5): 577-583, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-31361806

RESUMO

BACKGROUND: Platforms such as Instagram, Facebook, Twitter, and Google+ have created a worldwide audience of almost 3 billion people. Society is dramatically changing, demanding evolution of marketing strategies by plastic surgeons and aesthetic doctors alike. This unknown territory provides excellent opportunities, but creates many pitfalls as well; uncertainty remains as to the most effective manner to promote one's practice/services. OBJECTIVES: The aim of this study was to design a social experiment based on Instagram to give guidance for efficient self-promotion. METHODS: An Instagram account called "doctor.aesthetics" was created. Content was produced, and categorized into 4 groups: Aesthetics, Private Life, Disease, and Science. No bots or other Instagram-based promotion were utilized. Every post was evaluated regarding likes, comments, clicks, new followers, impressions, and savings. RESULTS: After 5 months and 37 posts, 10,500 people followed the account. "Scientific" posts were excluded from the analysis due to a low response rate. A significantly enhanced number of likes for "Private" postings was found. Additionally, "Private" posts led to most clicks and new followers, whereas "Aesthetics" posts were saved by most people. CONCLUSIONS: To benefit the most from social media advertising, it is necessary to offer insights into private life. Although "Aesthetics" and "Disease" postings showed similar response rates, "Scientific" posts failed to attract people.


Assuntos
Mídias Sociais , Cirurgiões , Humanos , Marketing , Estudos Prospectivos
20.
J Cell Physiol ; 234(12): 23097-23110, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31124125

RESUMO

Human adipose-derived stem cells (ASCs) have a potential for the treatment of peripheral nerve injury. Recent studies demonstrated that stem cells can mediate therapeutic effect by secreting exosomes. We aimed to investigate the effect of human ASCs derived exosomes (ASC-Exos) on peripheral nerve regeneration in vitro and in vivo. Our results showed after being internalized by Schwann cells (SCs), ASC-Exos significantly promoted SC proliferation, migration, myelination, and secretion of neurotrophic factors by upregulating corresponding genes in vitro. We next evaluated the efficacy of ASC-Exo therapy in a rat sciatic nerve transection model with a 10-mm gap. Axon regeneration, myelination, and restoration of denervation muscle atrophy in ASC-Exos treated group was significantly improved compared to vehicle control. This study demonstrates that ASC-Exos effectively promote peripheral nerve regeneration via optimizing SC function and thereby represent a novel therapeutic strategy for regenerative medicine and nerve tissue engineering.


Assuntos
Exossomos/genética , Transplante de Células-Tronco Mesenquimais , Atrofia Muscular/terapia , Regeneração Nervosa/genética , Traumatismos dos Nervos Periféricos/terapia , Animais , Axônios/metabolismo , Axônios/patologia , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Exossomos/transplante , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/patologia , Fibras Nervosas Mielinizadas/metabolismo , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/genética , Células de Schwann/transplante , Nervo Isquiático/crescimento & desenvolvimento , Nervo Isquiático/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA