Modulation of gene expression in skin wound healing by photobiomodulation therapy: A systematic review in vivo studies.

BACKGROUND: Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood. AIM: To systematically review publications that investigated gene expression after PBMT during in vivo skin repair. METHODS: An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used. RESULTS: Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF. CONCLUSION: This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood.

Immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by Staphylococcus aureus.

This work evaluated the immunomodulatory and anti-infective effects of Cratylia mollis lectin (Cramoll) in a model of wound infection induced by S. aureus. Swiss mice were divided into 3 groups (n = 12/group): non-inoculated (Control group); inoculated with S. aureus (Sa group); inoculated with S. aureus and treated with Cramoll (Sa + Cramoll group). In each animal, one lesion (64 mm2) was induced on the back and contaminated with S. aureus (~4.0 × 106 CFU/wound). The treatment with Cramoll (5 µg/animal/day) started 1-day post-infection (dpi) and extended for 10 days. Clinical parameters (wound size, inflammatory aspects, etc.) were daily recorded; while cytokines levels, bacterial load and histological aspects were determined in the cutaneous tissue at 4th dpi or 11th dpi. The mice infected with S. aureus exhibited a delay in wound contraction and the highest inflammatory scores. These effects were impaired by the treatment with Cramoll which reduced the release of key inflammatory mediators (TNF-α, NO, VEGF) and the bacterial load at wound tissue. Histological evaluations showed a restauration of skin structures in the animals treated with Cramoll. Taken together, these results provide more insights about the healing and immunomodulatory properties of Cramoll and suggest this lectin as a lead compound for treatment of wound infection.

Healing of dermal wounds property of Caryocar brasiliense oil loaded polymeric lipid-core nanocapsules: formulation and in vivo evaluation.

Cutaneous lesions lead to complications in patients, since they may be recurrent and also represent risk of progression to infection and/or amputation. Therefore, effective, protective, and topical treatments of easy application and removal need to be developed to provide effective alternatives to patients. The Caryocar brasiliense Cambess (CBC) presents important pharmacological activities and proved in the healing process. This paper reports the improvement of the CBC nanostructured (LNCCBC and LNCCBC+) activity in dermal wounds in vivo. The oil was physico-chemically characterized and used in the development of lipid-core nanocapsules (LNCs), coated (LNCCBC+) or without chitosan (LNCCBC), in concentration of 1.0 mg mL-1. Hydrogel (HG) was tested in vivo on lesions in the back of male Wistar rats for 14 days. The oil presented appropriate physico-chemical characteristics for its use, such as moisture 0.76 %, acidity 0.85 % and oleic acid 25.90 %. The LNCs showed nanometric size (around 200 nm), monomodal distribution, slight acid pH and zeta potential of + 22.1 mV in accordance with the composition. The nanostructured oil induced dermal healing in vivo showing significantly better improvement than free oil. LNCCBC+ showed best results showing the higher increase of the production of type 1 collagen, an important protein to the healing repair. These results suggest that development of formulations LNCCBC and LNCCBC+ are promising and important alternative for the treatment of dermal wounds, avoiding complications related to cutaneous lesions.

Engineered 3D-scaffolds of photocrosslinked chitosan-gelatin hydrogel hybrids for chronic wound dressings and regeneration.

Wound repair is one of the most complex biological processes in human life. To date, no ideal biomaterial solution has been identified, which that encompasses all functions and properties of real skin tissue. Thus, this study focused on the synthesis of new biocompatible hybrid hydrogel scaffolds based on methacrylate-functionalized high molecular mass chitosan with gelatin-A photocrosslinked with UV radiation to tailor matrix network properties. These hybrid hydrogels were produced via freeze-drying and were extensively characterized by swelling and degradation measurements, Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV-Vis), scanning electron microscopy (SEM-EDS), and micro-computed tomography (micro-CT). The results demonstrated that hydrogels were produced with broadly designed swelling degrees typically ranging from 500% to 2000%, which were significantly dependent on the relative concentration of polymers and irradiation time for crosslinking. Analogously, degradation was reduced with increased photocrosslinking of the network. Moreover, insights into the mechanism of photochemical crosslinking were suggested based on FTIR and UV-Vis analyses of the characteristic functional groups involved in the reactions. SEM analysis associated with micro-CT imaging of the hybrid scaffolds showed uniformly interconnected 3D porous structures, with architectural features affected by the crosslinking of the network. These hydrogels were biocompatible, with live cell viability responses of human embryonic kidney (HEK293T) cells being above 95%. Hence, novel hybrid hydrogels were designed and produced with tunable properties through photocrosslinking and with a biocompatible response suitable for use in wound dressing and skin tissue repair applications.

Connexin 43 deficiency accelerates skin wound healing and extracellular matrix remodeling in mice.

BACKGROUND: Cellular channels composed of connexin 43 are known to act as key players in the life cycle of the skin and consequently to underlie skin repair. OBJECTIVE: This study was specifically set up to investigate the suite of molecular mechanisms driven by connexin 43-based channels on wound healing. METHODS: To this end, a battery of parameters, including re-epithelialization, neovascularization, collagen deposition and extracellular matrix remodeling, was monitored over time during experimentally induced skin repair in heterozygous connexin 43 knockout mice. RESULTS: It was found that connexin 43 deficiency accelerates re-epithelialization and wound closure, increases proliferation and activation of dermal fibroblasts, and enhances the expression of extracellular matrix remodeling mediators. CONCLUSION: These data substantiate the notion that connexin 43 may represent an interesting therapeutic target in dermal wound healing.

Eletroestimulação na cicatrização de feridas cutâneas experimentais em coelhos / Electrical stimulation in experimental wound healing in rabbits

Feridas cutâneas crônicas e complicadas são frequentemente encontradas na rotina da medicina veterinária e, muitas vezes, transformam os tratamentos em verdadeiro desafio. A eletroterapia tem sido indicada como alternativa aos tratamentos convencionais, devido à sua capacidade de promover cicatrização. O objetivo deste trabalho é relatar um ensaio experimental utilizando a eletroestimulação (ES) na cicatrização de feridas cutâneas em coelhos. Para tanto, foram utilizados 10 coelhos Nova Zelândia, machos, hígidos, submetidos à anestesia geral para a indução experimental de duas feridas cutâneas de 1cm² localizadas no dorso, caudal à borda das escápulas. As lesões foram higienizadas com solução salina 0,9%, sendo a do lado direito tratada por ES e a do lado esquerdo, como controle. Para ES utilizou-se a frequência de 60Hz, por 10 minutos a cada dois dias, sendo aplicadas quatro agulhas de acupuntura em pontos equidistantes ao redor da lesão, a 0,5cm da borda. Os animais foram divididos em dois grupos, de oito e de 15 dias, conforme o período de tratamento e avaliação macroscópica e histopatológica. Não houve diferença significativa no tempo de cicatrização das lesões tratadas com ES. Porém, apresentaram qualidade tecidual, tanto na avaliação macro quanto microscópica, superior às do grupo controle. Com isso, é possível indicar a ES como tratamento de feridas cutâneas, por ser uma técnica eficiente, de fácil aplicação e de relativo baixo custo.(AU)

Chronic skin wounds are frequently found in veterinary medicine routine and it becomes a challenge for clinicians. Sometimes the treatment routinely used end up failing. The electrotherapy has been indicated as an alternative to conventional treatments because of its ability to promote healing. The aim of this paper is to report an experimental study using electrical stimulation (ES) in wound healing in rabbits. It was evaluated 10 healthy New Zealand rabbits that were submitted to general anesthesia for resection of two wounds with 1cm² located in both sides of the back behind the scapula edge. It was determinate that the right wound would be treated by ES and the left would be used as a control, both cleaned with solution of NaCl 0,9%. The frequency used to ES was 60Hz for 10 minutes every two days, being applied by acupuncture needles in four equidistant points around the lesion, to 0.5cm from the edge. The animals were divided in one group of 15 days and another one of 8 days for treatment and macroscopic and histopathological evaluation. The results showed that the lesions treated by ES do not have significant difference in healing time. However, those treated had higher scarring macroscopic and microscopic quality than the control group. Therefore, it is possible to indicate the use of ES as a skin wounds treatment, whereas it was demonstrated to be an effective technique, easy to use and has relatively low cost.(AU)

Eletroestimulação na cicatrização de feridas cutâneas experimentais em coelhos / Electrical stimulation in experimental wound healing in rabbits

Feridas cutâneas crônicas e complicadas são frequentemente encontradas na rotina da medicina veterinária e, muitas vezes, transformam os tratamentos em verdadeiro desafio. A eletroterapia tem sido indicada como alternativa aos tratamentos convencionais, devido à sua capacidade de promover cicatrização. O objetivo deste trabalho é relatar um ensaio experimental utilizando a eletroestimulação (ES) na cicatrização de feridas cutâneas em coelhos. Para tanto, foram utilizados 10 coelhos Nova Zelândia, machos, hígidos, submetidos à anestesia geral para a indução experimental de duas feridas cutâneas de 1cm² localizadas no dorso, caudal à borda das escápulas. As lesões foram higienizadas com solução salina 0,9%, sendo a do lado direito tratada por ES e a do lado esquerdo, como controle. Para ES utilizou-se a frequência de 60Hz, por 10 minutos a cada dois dias, sendo aplicadas quatro agulhas de acupuntura em pontos equidistantes ao redor da lesão, a 0,5cm da borda. Os animais foram divididos em dois grupos, de oito e de 15 dias, conforme o período de tratamento e avaliação macroscópica e histopatológica. Não houve diferença significativa no tempo de cicatrização das lesões tratadas com ES. Porém, apresentaram qualidade tecidual, tanto na avaliação macro quanto microscópica, superior às do grupo controle. Com isso, é possível indicar a ES como tratamento de feridas cutâneas, por ser uma técnica eficiente, de fácil aplicação e de relativo baixo custo.

Chronic skin wounds are frequently found in veterinary medicine routine and it becomes a challenge for clinicians. Sometimes the treatment routinely used end up failing. The electrotherapy has been indicated as an alternative to conventional treatments because of its ability to promote healing. The aim of this paper is to report an experimental study using electrical stimulation (ES) in wound healing in rabbits. It was evaluated 10 healthy New Zealand rabbits that were submitted to general anesthesia for resection of two wounds with 1cm² located in both sides of the back behind the scapula edge. It was determinate that the right wound would be treated by ES and the left would be used as a control, both cleaned with solution of NaCl 0,9%. The frequency used to ES was 60Hz for 10 minutes every two days, being applied by acupuncture needles in four equidistant points around the lesion, to 0.5cm from the edge. The animals were divided in one group of 15 days and another one of 8 days for treatment and macroscopic and histopathological evaluation. The results showed that the lesions treated by ES do not have significant difference in healing time. However, those treated had higher scarring macroscopic and microscopic quality than the control group. Therefore, it is possible to indicate the use of ES as a skin wounds treatment, whereas it was demonstrated to be an effective technique, easy to use and has relatively low cost.

The energy density of laser light differentially modulates the skin morphological reorganization in a murine model of healing by secondary intention.

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2).