Effect of laser dose and treatment schedule on excision wound healing in diabetic mice

The present study was undertaken to evaluate a He-Ne laser (632.8 nm; 7 mW; 4.02 mW cm(-2); 15 mm spot size) dose and the treatment schedule on diabetic wound healing in a mouse model. Circular wounds of 15 mm diameter were created on streptozotocin induced diabetic Swiss albino mice, and were uniformly illuminated with the single exposure of various He-Ne laser doses of 1, 2, 3, 4 and 5 J cm(-2) respectively. Further, the treatment schedule was also optimized by exposing the wounds with 3 J cm(-2) at 0, 24 h, 48 h postwounding. Contraction kinetics, mean area under the curve and the mean healing time of the wounds were computed along with the collagen and the glucosamine levels in the wound ground tissues at various postwounding treatment schedules. Results of this study indicated that the single exposure of 3 J cm(-2) laser dose applied immediately after the wounding caused a significant reduction in the mean area under the curve and the mean healing time along with the elevated levels of collagen and glucosamine contents in the tissue compared to the controls. In conclusion, He-Ne laser dose of 3 J cm(-2) applied immediately after the wounding has demonstrated optimum wound healing compared to the other doses and treatment schedules.     

Nanoparticle-based therapeutic approaches for wound healing: a review of the state-of-the-art

Wound healing is a complex physiological procedure that includes diverse stages, comprising hemostasis, inflammation, proliferation, and remodeling to reconstruct the skin and subcutaneous tissue's integrity. As reported, various coexisting diseases (diabetes, vascular diseases, etc.) substantially impact wound healing. Factors like recurring injury, age, or hypertrophic scarring also affect wound healing. The management of wound care depends primarily on the advancement of novel and efficient wound dressing substances, and it persists to be a vivid research area in chronic wound healing. Over the past years, the investigation and advancement of wound dressing biomaterials have registered a new standard level, and superior knowledge based on chronic wound pathogenesis has been achieved. Recently, nanotechnology has presented an excellent method to accelerate acute and chronic wound healing via stimulating appropriate movement through the diverse healing stages. Among various nanomaterials, nanoparticles (NPs) have been spotlighted as an efficient treatment strategy for wound healing due to their ability to act as both a therapeutic and carrier system. Their small size and high surface area to volume ratio enhance the probability of bio-interaction and penetration at the wound area aiding cell–cell interactions, the proliferation of cells, cell signaling, and vascularization. This review endeavored to throw light on different aspects of wounds and the latest advances in nanoparticle-based biomaterials for effective wound healing. Further, challenges and future potentialities have been addressed.     

Influence of laser photobiomodulation upon connective tissue remodeling during wound healing

The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm(2)) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (p<0.05). An evident increase in the number of actin-positive cells was observed in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.     

Comparison of Pulsed and Continuous Wave Diode Laser at 940 nm on the Viability and Migration of Gingival Fibroblasts

Gingival fibroblasts have critical roles in oral wound healing. Photobiomodulation (PBM) has been shown to promote mucosal healing and is now recommended for managing oncotherapy-associated oral mucositis. This study examined the effects of the emission mode of a 940 nm diode laser on the viability and migration of human gingival fibroblasts. Cells were cultured in a routine growth media and treated with PBM (average power 0.1 W cm⁻², average fluence 3 J cm⁻², every 12 h for six sessions) in one continuous wave and two pulsing settings with 20% and 50% duty cycles. Cell viability was assessed using MTT, and digital imaging quantified cell migration. After 48 and 72 h, all treatment groups had significantly higher viability (n = 6, P < 0.05) compared with the control. The highest viability was seen in the pulsed (20% duty cycle) group at the 72-h time point. PBM improved fibroblast migration in all PBM-treated groups, but differences were not statistically significant (n = 2, P > 0.05). PBM treatments can promote cell viability in both continuous and pulsed modes. Further studies are needed to elucidate the optimal setting for PBM-evoked responses for its rationalized use in promoting specific phases of oral wound healing.     

Titanium Nanorods Loaded PCL Meshes with Enhanced Blood Vessel Formation and Cell Migration for Wound Dressing Applications

Proper management of nonhealing wounds is an imperative clinical challenge. For the effective healing of chronic wounds, suitable wound coverage materials with the capability to accelerate cell migration, cell proliferation, angiogenesis, and wound healing are required to protect the healing wound bed. Biodegradable polymeric meshes are utilized as effective wound coverage materials to protect the wounds from the external environment and prevent infections. Among them, electrospun biopolymeric meshes have got much attention due to their extracellular matrix mimicking morphology, ability to support cell adhesion, and cell proliferation. Herein, electrospun nanocomposite meshes based on polycaprolactone (PCL) and titanium dioxide nanorods (TNR) are developed. TNR incorporated PCL meshes are fabricated by electrospinning technique and characterized by scanning electron microscopy, energy dispersive X‐ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) analysis, and X‐Ray diffraction (XRD) analysis. In vitro cell culture studies, in ovo angiogenesis assay, in vivo implantation study, and in vivo wound healing study are performed. Interestingly, obtained in vitro and in vivo results demonstrated that the presence of TNR in the PCL meshes greatly improved the cell migration, proliferation, angiogenesis, and wound healing. Owing to the above superior properties, they can be used as excellent biomaterials in wound healing and tissue regeneration applications.     

Effect of low-level helium-neon laser therapy on the healing of third-degree burns in rats

This paper presents the results of a study on the effects of low-level helium-neon laser therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult male rats, having been subjected to third-degree burns, were randomly divided into four groups: two laser treated groups (n=20, each), one control group (n=19) and one nitrofurazone treated group (n=19). In the two laser treated groups, the burns were treated on a daily basis with LL He-Ne LT with an energy density of 1.2 and 2.4 J/cm(2), respectively. The response to treatment was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at day 15. Analysis of variance showed that the mean of blood vessel sections in the 1.2J/cm(2) laser group was significantly higher than those in the other groups and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group on day 16 was significantly lower than in the nitrofurazone treated group (P=0.025, P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa grew in more than 50% of samples obtained from control group, there were no S. aureus and P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is concluded that LL He-Ne LT induced the destruction of S. aureus and P. aeruginosa in third-degree burns of rats, yet at the same time our histological findings showed that LL He-Ne LT caused a significant increase in the mean of blood vessel sections on day 7 after third degree burns and a decrease in the mean of the depth of new epidermis on day 16 after the same burns in rats.     

Development and Evaluation of Fiber Optic Probe-based Helium–Neon Low-level Laser Therapy System for Tissue Regeneration—An In Vivo Experimental Study

We report the design and development of an optical fiber probe-based Helium–Neon (He–Ne) low-level laser therapy system for tissue regeneration. Full thickness excision wounds on Swiss albino mice of diameter 15 mm were exposed to various laser doses of 1, 2, 3, 4, 6, 8 and 10 J cm⁻² of the system with appropriate controls, and 2 J cm⁻² showing optimum healing was selected. The treatment schedule for applying the selected laser dose was also standardized by irradiating the wounds at different postwounding times (0, 24 and 48 h). The tissue regeneration potential was evaluated by monitoring the progression of wound contraction and mean wound healing time along with the hydroxyproline and glucosamine estimation on wound ground tissues. The wounds exposed to 2 J cm⁻² immediately after wounding showed considerable contraction on days 5, 9, 12, 14, 16 and 19 of postirradiation compared with the controls and other treatment schedules, showing significant (P < 0.001) decrease in the healing time. A significant increase in hydroxyproline and glucosamine levels was observed for the 2 J cm⁻² irradiation group compared with the controls and other treatment groups. In conclusion, the wounds treated with 2 J cm⁻² immediately after the wounding show better healing compared with the controls.     

Effect of low-level laser therapy on the healing of second-degree burns in rats: a histological and microbiological study

This paper presents the results of a study on the effects of two different doses of low-level laser therapy on healing of deep second-degree burns. Sixty rats were randomly allocated to one of four groups. A deep second-degree burn was inflicted in each rat. In the control group burns remained untreated; in two laser treated groups the burns were irradiated daily with low-level helium-neon laser with energy densities of 1.2 and 2.4 J/cm2, respectively. In the fourth group the burns were treated topically with 0.2% nitrofurazone cream every day. The response to treatments was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at Day 15. The number of macrophages at day 16, and the depth of new epidermis at day 30, was significantly less in the laser treated groups in comparison with control and nitrofurazone treated groups (P=0.000). Staphylococcus epidermidis was found in the 70% of rat wounds in the laser treated groups in comparison with 100% of rats in the control group. S. aureus was found in the 40% rat wounds in the nitrofurazone treated group, but there was not found in the wounds of laser treated, and control groups. It is concluded that low-level laser therapy of deep second-degree burn caused significant decrease in the number of macrophage and depth of new epidermis. In addition, it decreased incidence of S. epidermidis and S. aureus.     

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.     

Effect of a topical formulation containing Calophyllum brasiliense Camb. extract on cutaneous wound healing in rats

This study evaluated the wound healing effects of topical application of an emulsion containing the HPLC-standardised extract from Calophyllum brasiliense Cambess (Clusiaceae) leaves in rats. The macroscopic analysis demonstrated that the wounds treated with the C. brasiliense emulsion healed earlier than the wounds treated with emulsion base and Dersani®. The percentage of wound healing in the group treated with the C. brasiliense emulsion was significantly higher than in the other groups at 7 and 14 days. On day 14, the animals treated with the C. brasiliense emulsion exhibited a 90.67% reduction of the wound areas. The histological evaluation revealed that on day 21, the group treated with the C. brasiliense emulsion exhibited a significant increase in fibroblasts compared with the other groups. Thus, the C. brasiliense emulsion had healing properties in the topical treatment of wounds and accelerated the healing process.     

Ultrastructural and autoradiographical analysis show a faster skin repair in He-Ne laser-treated wounds

There are evidences that low-intensity red laser radiation is capable to accelerate wound healing. Nowadays, this therapy has been gradually introduced in clinical practice although mechanisms underlying laser effects are poorly understood. To better understand the photobiological effects of laser radiation, this study investigated by electron microscopy, immunohistochemistry and autoradiography the morphological and functional features of irradiated and none irradiated injured mice skin. Full-thickness skin lesions were created on the back of mice and irradiated on days 1, 5, 8, 12, and 15 post-wounding with a He-Ne laser (lambda=632.8nm), dose 1J/cm(2), exposure time 3min. Non-irradiated lesions were used as a control. The mice were inoculated with (3)H-proline and sacrificed one hour after on the 8th, 15th and 22nd days to histological and radioautographical analysis. The irradiated-lesions showed a faster reepithelization compared with control lesions. The irradiated dermis contained a higher number of activated fibroblasts compared to control group and, most of them showed several cytoplasmic collagen-containing phagosomes. In irradiated-lesions, smooth muscle alpha-actin positive cells predominated, which correspond to a higher number of myofibroblasts observed in the electron microscope. Moreover, laser radiation reduced the local inflammation and appears to influence the organization of collagen fibrils in the repairing areas. Quantitative autoradiography showed that the incorporation of (3)H-proline was significantly higher in irradiated-dermis on the 15th day post-wounding (p<0.05). These results suggest that laser radiation may accelerate cutaneous wound healing in a murine model.     

Effect of laser phototherapy on wound healing following cerebral ischemia by cryogenic injury

Laser phototherapy emerges as an alternative or auxiliary therapy for acute ischemic stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, but its effects are still controversial. We have previously found that laser phototherapy immunomodulates the response to focal brain damage. Following direct cortical cryogenic injury the effects of laser phototherapy on inflammation and repair was assessed after cryogenic injury (CI) to the central nervous system (CNS) of rats. The laser phototherapy was carried out with a 780 nm AlGaAs diode laser. The irradiation parameters were: power of 40 mW, beam area of 0.04 cm(2), energy density of 3 J/cm(2) (3s) in two points (0.12 J per point). Two irradiations were performed at 3 h-intervals, in contact mode. Rats (20 non-irradiated - controls and 20 irradiated) were used. The wound healing in the CNS was followed in 6 h, 1, 7 and 14 days after the last irradiation. The size of the lesions, the neuron cell viability percentages and the amount of positive GFAP labeling were statistically compared by ANOVA complemented by Tukey's test (p<0.05). The distribution of lymphocytes, leukocytes and macrophages were also analyzed. CI created focal lesions in the cortex represented by necrosis, edema, hemorrhage and inflammatory infiltrate. The most striking findings were: lased lesions showed smaller tissue loss than control lesions in 6 h. During the first 24 h the amount of viable neurons was significantly higher in the lased group. There was a remarkable increase in the amount of GFAP in the control group by 14 days. Moreover, the lesions of irradiated animals had fewer leukocytes and lymphocytes in the first 24 h than controls. Considering the experimental conditions of this study it was concluded that laser phototherapy exerts its effect in wound healing following CI by controlling the brain damage, preventing neuron death and severe astrogliosis that could indicate the possibility of a better clinical outcome.     

In vivo monitoring the changes of interstitial pH and FAD/NADH ratio by fluorescence spectroscopy in healing skin wounds

The aim of our study was to evaluate the changes of interstitial pH and flavin adenine dinucleotide (FAD)/reduced nicotinamide adenine dinucleotide (NADH) ratio in healing skin wounds using fluorescence spectroscopy in Sprague Dawley rats. In the experiment, excisional and incisional models of wound healing were used. The florescein as the pH-sensitive probe using excitation spectra (lambda(Em) = 535 nm) was used for the measurement of pH changes, and synchronous fluorescence spectra (Deltalambda = 60 nm) for the monitoring of FAD/NADH ratio changes were measured from the surfaces of healing wounds. Increase of interstitial pH and FAD/NADH ratio was recorded during the time interval from the 15th to the 65th minute after surgery. The decrease of pH between the 48th and the 72nd hour after surgery as well as the increase of FAD/NADH ratio between the 72nd and the 96th hour of wound healing were recorded. The results indicate that the use of fluorescence spectroscopy may be considered as a valuable tool for noninvasive in vivo monitoring of selected redox parameters in the early phases of wound healing.     

The Unexplored Wound Healing Activity of Urtica dioica L. Extract: An In Vitro and In Vivo Study

Wound healing is a great challenge in many health conditions, especially in non-healing conditions. The search for new wound healing agents continues unabated, as the use of growth factors is accompanied by several limitations. Medicinal plants have been used for a long time in would healing, despite the lack of scientific evidence veryfying their efficacy. Up to now, the number of reports about medicinal plants with wound healing properties is limited. Urtica dioica L. is a well-known plant, widely used in many applications. Reports regarding its wound healing potential are scant and sparse. In this study, the effect of an Urtica dioica L. extract (containing fewer antioxidant compounds compared to methanolic or hydroalcoholic extracts) on cell proliferation, the cell cycle, and migration were examined. Additionally, antioxidant and anti-inflammatory properties were examined. Finally, in vivo experiments were carried out on full-thickness wounds on Wistar rats. It was found that the extract increases the proliferation rate of HEK-293 and HaCaT cells up to 39% and 30% after 24 h, respectively, compared to control cells. The extract was found to increase the population of cells in the G₂/M phase by almost 10%. Additionally, the extract caused a two-fold increase in the cell migration rate of both cell lines compared to control cells. Moreover, the extract was found to have anti-inflammatory properties and moderate antioxidant properties that augment its overall wound healing potential. Results from the in vivo experiments showed that wounds treated with an ointment of the extract healed in 9 days, while wounds not treated with the extract healed in 13 days. Histopathological examination of the wound tissue revealed, among other findings, that inflammation was significantly reduced compared to the control. Urtica dioica L. extract application results in faster wound healing, making the extract ideal for wound healing applications and a novel drug candidate for wound healing.     

Effect of Ga-As (904nm) and He-Ne (632.8 nm) laser on injury potential of skin full-thickness wound

Injury potential may have a triggering biological role in wound healing. In this study, the effect of photostimulation to promote wound healing and its effect on injury potential was investigated using the Ga-As and He-Ne lasers. In this study, 30 healthy male Sprague-Dawley rats were randomly divided into a control and two laser groups, He-Ne and Ga-As laser. A 2.5 cm craniocaudal full-thickness skin incision was made on each animal's dorsal region. Differential skin surface potential was measured before and immediately after the injury and also up to the 21st day, every other day. Wound surface area was also measured. Immediately after injury, wound potential significantly increased in all three groups. Maximum positive peak of injury potential was greater in Ga-As group compared to He-Ne laser and control groups (P<0.05) and lasting period of maximum positive potential in two laser groups was longer than that in the control group. There were no significant differences between the mean potential of before wounding and after the 15th, 17th, and 19th day in Ga-As, He-Ne, and control group, respectively (P>0.05). On the other hand, Ga-As and He-Ne laser facilitated the normal distribution of skin potential after wounding. These findings demonstrate that Ga-As laser may be more effective on wound closure and on returning the injury potential to normal level than the He-Ne laser.     

Effect of low intensity helium-neon (HeNe) laser irradiation on experimental paracoccidioidomycotic wound healing dynamics

The effect of HeNe laser on the extracellular matrix deposition, chemokine expression and angiogenesis in experimental paracoccidioidomycotic lesions was investigated. At days 7, 8 and 9 postinfection the wound of each animal was treated with a 632.8 nm HeNe laser at a dose of 3 J cm(-2). At day 10 postinfection, the wounds were examined by using histologic and immunohistochemical methods. Results revealed that laser-treated lesions were lesser extensive than untreated ones, and composed mainly by macrophages and lymphocytes. High IL-1beta expression was shown in the untreated group whereas in laser-treated animals the expression was scarce. On the other hand, the expression of CXCL-10 was found to be reduced in untreated animals and quite intensive and well distributed in the laser-treated ones. Also, untreated lesions presented vascular endothelial growth factor (VEGF) in a small area near the center of the lesion and high immunoreactivity for hypoxia-inducible factor-1 (HIF-1), whereas laser-treated lesions expressed VEGF surrounding blood vessels and little immunoreactivity for HIF-1. Laser-treated lesions presented much more reticular fibers and collagen deposition when compared with the untreated lesion. Our results show that laser was efficient in minimizing the local effects observed in paracoccidioidomycosis and can be an efficient tool in the treatment of this infection, accelerating the healing process.     

Role of Macromolecules in Medical Application: Challenges and Opportunities

The concept of macromolecules, which is applied to synthetic and natural polymers, allows for various contemporary polymeric materials and inventive uses. A dynamic structure of macromolecules called the extracellular matrix (ECM) maintains tissues and organs functioning. The cell therapy procedure known as wound healing involves depositing ECM components such as collagen, fibronectin, and laminin. The clinical assessment and management of wounds remain challenging despite the introduction of numerous therapeutic regimens because of their laboriously prolonged treatment requirements and complex wound-healing mechanisms using macromolecules of a specific type, such as proteins, carbohydrates, lipids, and nucleic acids. Additionally, proteins affect the wound site's mechanical characteristics, such as tensile strength, elasticity, and permeability, which impact the effectiveness and success of wound healing. The main goal of this article is to give a current overview of how therapeutic alternatives have evolved using cutting-edge innovative techniques for the healing and treatment of wounds. In this article, we have covered different types of macromolecules, how diet affects the wound, what causes wounds, and how macromolecules can help, and how to treat wounds.     

Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary findings on time-dependent T1-weighted contrast-enhanced magnetic resonance imaging (MRI)

Laser therapy by low light doses shows promising results in the modulation of some cell functions. Various clinical studies indicate that laser therapy is a valuable method for pain treatment and the acceleration of wound healing. However, the mechanism behind it is still not completely understood. To explore the effect of a low-power diode laser (lambda = 780 nm) on normal skin tissue, time-dependent contrast enhancement has been determined by magnetic resonance imaging (MRI). In the examinations, six healthy volunteers (four male and two female) have been irradiated on their right planta pedis (sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic resonance imaging is used to quantify the time-dependent local accumulation of Gadolinium-DPTA, its actual content in the local current blood volume as well as its distribution to the extracellular space. Images are obtained before and after the application of laser light. When laser light is applied the signal to noise ratio increases by more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrast-enhanced MRI. It can be observed that, after biomodulation with light of low energy and low power, wound healing improves and pain is reduced. This effect might be explained by an increased blood flow in this area. Therefore, the use of this kind of laser treatment might improve the outcome of other therapeutic modalities such as tumour ionizing radiation therapy and local chemotherapy.     

Acidified Nitrite Accelerates Wound Healing in Type 2 Diabetic Male Rats: A Histological and Stereological Evaluation

Impaired skin nitric oxide production contributes to delayed wound healing in type 2 diabetes (T2D). This study aims to determine improved wound healing mechanisms by acidified nitrite (AN) in rats with T2D. Wistar rats were assigned to four subgroups: Untreated control, AN-treated control, untreated diabetes, and AN-treated diabetes. AN was applied daily from day 3 to day 28 after wounding. On days 3, 7, 14, 21, and 28, the wound levels of vascular endothelial growth factor (VEGF) were measured, and histological and stereological evaluations were performed. AN in diabetic rats increased the numerical density of basal cells (1070 ± 15.2 vs. 936.6 ± 37.5/mm³) and epidermal thickness (58.5 ± 3.5 vs. 44.3 ± 3.4 μm) (all p < 0.05); The dermis total volume and numerical density of fibroblasts at days 14, 21, and 28 were also higher (all p < 0.05). The VEGF levels were increased in the treated diabetic wounds at days 7 and 14, as was the total volume of fibrous tissue and hydroxyproline content at days 14 and 21 (all p < 0.05). AN improved diabetic wound healing by accelerating the dermis reconstruction, neovascularization, and collagen deposition.     

Specific Features of Early Stage of the Wound Healing Process Occurring Against the Background of Photodynamic Therapy Using Fotoditazin Photosensitizer–Amphiphilic Polymer Complexes

There is a growing demand on the studies of the wound healing potentials of photodynamic therapy. Here we analyze the effects of Fotoditazin, an e6 chlorine derivative, and its complexes with amphiphilic polymers, on the early stage of wound healing in a rat model. A skin excision wound model with prevented contraction was developed in male albino rats divided into eight groups according to the treatment mode. All animals received injections of one of the studied compositions into their wound beds and underwent low‐intensity laser irradiation or stayed un‐irradiated. The clinical monitoring and histological examination of the wounds were performed. It has been found that all the Fotoditazin formulations have significant effects on the early stage of wound healing. The superposition of the inflammation and regeneration was the main difference between groups. The aqueous solution of Fotoditazin alone induced a significant capillary hemorrhage, while its combinations with amphiphilic polymers did not. The best clinical and morphological results were obtained for the Fotoditazin–Pluronic F127 composition. Compositions of Fotoditazin and amphiphilic polymers, especially Pluronic F127, probably, have a great potential for therapy of wounds. Their effects can be attributed to the increased regeneration and suppressed reactions changes at the early stages of repair.