Ana Cristina Gonzalez

Wound healing - A literature review

Regeneration and tissue repair processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. The exsudative, proliferative, and extracellular matrix remodeling phases are sequential events that occur through the integration of dynamic processes involving soluble mediators, blood cells, and parenchymal cells. Exsudative phenomena that take place after injury contribute to the development of tissue edema. The proliferative stage seeks to reduce the area of tissue injury by contracting myofibroblasts and fibroplasia. At this stage, angiogenesis and reepithelialization processes can still be observed. Endothelial cells are able to differentiate into mesenchymal components, and this difference appears to be finely orchestrated by a set of signaling proteins that have been studied in the literature. This pathway is known as Hedgehog. The purpose of this review is to describe the various cellular and molecular aspects involved in the skin healing process.

Influence of the HPA axis on the inflammatory response in cutaneous wounds with the use of 670-nm laser photobiomodulation.

This study evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis in cutaneous wounds subjected to laser biomodulation. A total of 48 rats were divided into two groups: Group I (GI) with 24 adrenalectomized animals and Group II (GII) with 24 non-adrenalectomized animals. Each group was divided into two subgroups: the irradiated subgroup which laser was applied to four points at the edges of the wound (670 nm laser, 9 mW) and control subgroup. Rats in each subgroup were sacrificed at 24 or 72 h. Adrenal glands were only removed from GI rats. Three days after adrenalectomy, a cutaneous wound was made. An immunohistochemical analysis was performed using anti-CD45 and anti-CD8 antibodies. Flow cytometry was used to count T lymphocytes and their subpopulations in blood. Decreases in the number of CD45-positive inflammatory cells and in the total numbers of CD8- and CD45-positive cells were observed in histological sections of adrenalectomized animals subjected to laser biomodulation at 24h. Similar results were observed for distribution of total lymphocytes in blood (p<0.05). The action of 670 nm laser does not depend exclusively on HPA axis. It is believed that corticosteroid-promoting enzymes liberated in non-adrenal tissues may influence immune response under the influence of this type of phototherapy.

BIOMODULATORY POTENTIAL OF LOW-LEVEL LASER ON NEOANGIOGENESIS AND REMODELING TISSUE. A LITERATURE REVIEW

| Introduction: In recent years, cellular biostimulation induced by low-level laser therapy has been widely studied. Among some of the processes stimulated by low-level laser are cell cycle, phenotypic modulation as well as vascular changes, such as vasodilation and neoangiogenesis. The increased number of new blood vessels accelerates inflammation, and also increases wound healing. Neoangiogenesis is still an important process of tissue repair, since it always precedes collagen synthesis and matrix extracellular remodeling. Increasing scientific evidence has shown that photobiomodulation stimulates neoangiogenesis, fibroblast proliferation and collagen biosynthesis. Objective: Review the literature about the effects of low level laser therapy on neoangiogenesis and fibroplasia and describe how these processes occur in the tissue subjected to an injury. Methods and Matereials: The search tool used was the Medline / Pubmed and the following keywords were used: remodeling, wound healing, neoangiogenesis, fibroplasia, laser therapy, low-level laser. Manuscripts published from 1990 to 2017 were selected. Results: Increasing scientific evidence has shown that photobiomodulation stimulates neoangiogenesis, fibroblast proliferation and collagen biosynthesis. Conclusion: Neoangiogenesis always precedes collagen synthesis and matrix extracellular remodeling. However, little is known of the action of laser therapy in the late stages of tissue repair.

Effect of 670 nm laser photobiomodulation on vascular density and fibroplasia in late stages of tissue repair

This study aimed to investigate the effects of gallium‐aluminum‐arsenium (GaAlAs) (670 nm) laser therapy on neoangiogenesis and fibroplasia during tissue remodelling. Forty male Wistar rats underwent cutaneous surgery and were divided into 2 experimental groups: the Control and Laser group (9 mW, 670 nm, 0.031 W/cm2, 4 J/cm2). After 14, 21, 28, and 35 days, the animals were euthanised. Descriptive and quantitative analyses were performed in sections stained with haematoxylin‐eosin and Sirius Red, respectively. The amounts of VEGF+ and CD31+ cells were evaluated by immunohistochemistry and histomorphometric analysis, respectively. Statistical analysis was performed using the Mann‐Whitney, Friedman, and Spearman correlation test, P < 0.05. The collagen expression was significantly higher in the laser group compared with the control group on days 14 and 21 after the creation of the skin wound (P = 0.008; P = 0.016) and in the control group between 14 and 28 and 14 and 35 days (P = 0.001; P = 0.007). There were more blood vessels in three periods of the study only in the (Laser) treated group, with statistical significance at day 14 (P = 0.016). There was no statistically significant difference in VEGF+ cell count in the different experimental groups throughout the study, although a positive correlation was shown with the area of collagen on days 14 and 28 (P = 0.037). Laser treatment had a positive effect in the late course of healing, particularly with regards to collagen expression and the number of newly formed vessels. VEGF+ cells were present in both experimental groups, and VEGF appeared to influence fibroplasia in the treated group.

Immunohistochemical evaluation of hedgehog signalling in epithelial/mesenchymal interactions in squamous cell carcinoma transformation: a pilot study.

Precancerous lesions have been studied because of their carcinogenic potential and their association with squamous cell carcinoma (SCC) has been reported. In the tumour microenvironment, the processes of angiogenesis and tissue remodelling are regulated by a family of proteins (Hedgehog) described as being able to modulate epithelial/mesenchymal interactions. The objective of this study was to perform a comparative study of precancerous lesions and SCCs by immunohistochemistry for the presence of Sonic, Gli2, SMO and Patched proteins, members of the Hedgehog pathway. Sixteen cases diagnosed as actinic cheilitis associated with SCC were compared to normal oral mucosa. The sections were subjected to immunohistochemistry and the positively stained cells were counted by morphometric analysis. There was a significant progressive increase in expression of all proteins of the Hedgehog pathway, both in the epithelium and in the connective tissue, when sections of normal mucosa, dysplasia and carcinoma were compared (P < 0.05). Thus, one may suggest that the Hedgehog pathway in tumour transformation influences SCC, and more studies should be conducted to expand the understanding of the role of these proteins in neoplastic transformation.