scholarly journals Effects of Extracorporeal Shock Waves on Microcirculation and Angiogenesis in the in vivo Wound Model of the Diver Box

2021 ◽  
pp. 1-10
Author(s):  
Heiko Sorg ◽  
Inga Zwetzich ◽  
Daniel Johannes Tilkorn ◽  
Jonas Kolbenschlag ◽  
Jörg Hauser ◽  
...  

<b><i>Introduction:</i></b> Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the different application modes. <b><i>Methods:</i></b> A total of 40 BALB/c mice were provided with dorsal skin fold chambers and were divided into 3 therapy groups (<i>n</i> = 30) and one control group (<i>n</i> = 10). The 3 therapy groups were treated with shock waves at different pulse rates (500–1,000 pulses/min) and application frequencies (day 0 and day 6 or day 0 only). Photographic documentation and intravital microscopy were carried out on day 1, 2, 4, and 6 after wounding. <b><i>Results:</i></b> Using the newly developed Diver Box, shock waves could be applied in vivo without mechanical tissue damage. Shock wave therapy to skin wounds demonstrated to induce faster wound closure rates in the beginning than controls in groups with higher pulse rates and frequencies of the shock waves. Furthermore, the regeneration of microcirculation and perfusion in the healing skin was significantly improved after the application of, in particular, higher pulse rates as given by increased numbers of perfused capillaries and functional vessel density. The study of inflammation showed, especially in high-pulse ESW groups, higher leukocyte counts, and rolling leukocytes over time until day 6 as a response to the induction of inflammatory reaction after ESW application. Angiogenesis showed a marked increase in positive areas as given by sprouts, coils, and recruitments in all ESW groups, especially between days 4 and 6. <b><i>Conclusion:</i></b> The major findings of this trial demonstrate that ESW therapy to skin wounds is effective and safe. This is demonstrated by the initially faster wound closure rate, but later the same wound closure rate in the treatment groups than in controls. Furthermore, during the regeneration of microcirculation and perfusion in the healing skin, a significant improvement was observed after the application of, in particular, higher ESW pulse rates, suggesting an ESW-related increase in nutrient and oxygen supply in the wound tissue.

Author(s):  
Fahim M. Mahmood ◽  
Hayder B. Sahib ◽  
Khalid W. Qassim

Wound healing is a complex physiological and dynamic process required the coordination of numerous cell types and biological processes to regenerate damaged tissue and initiate repair which is dependent on a number of inter-related factors. This study was aimed to demonstrate whether the ?2 receptor has role in wound healing and angiogenesis. A murine wild-type (in vivo), excisional skin wound model was done to demonstrate that activation of ?2AR delay wound repair, twenty-four male albino mice were used to investigate the effect of the drug on experimental wound healing grossly, histo-pathologically and immune-histochemically compared with vehicle-only controls. The results showed that the rate of wound healing was significantly slower in salbutamol group than in control group (P


2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.


2019 ◽  
Vol 5 (7) ◽  
pp. eaaw3963 ◽  
Author(s):  
S. O. Blacklow ◽  
J. Li ◽  
B. R. Freedman ◽  
M. Zeidi ◽  
C. Chen ◽  
...  

Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 222
Author(s):  
Suneel Kumar ◽  
Yuying Tan ◽  
Francois Berthiaume

Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10−7 M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Luciana S. Altoé ◽  
Raul S. Alves ◽  
Lyvia L. Miranda ◽  
Mariáurea M. Sarandy ◽  
Daniel S. S. Bastos ◽  
...  

The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect of Dx on inflammatory cell recruitment and production of inflammatory mediators via in vitro and in vivo analysis. In addition, we analyzed neovascularization, extracellular matrix deposition, and antioxidant potential of Dx on cutaneous repair in Wistar rats. Male animals ( n = 15 ) were divided into three groups with five animals each (protocol: 72/2017), and three skin wounds (12 mm diameter) were created on the back of the animals. The groups were as follows: C, received distilled water (control); Dx1, doxycycline hyclate (10 mg/kg/day); and Dx2, doxycycline hyclate (30 mg/kg/day). The applications were carried out daily for up to 21 days, and tissues from different wounds were removed every 7 days. Our in vitro analysis demonstrated that Dx led to macrophage proliferation and increased N-acetyl-β-D-glucosaminidase (NAG) production, besides decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and metalloproteinases (MMP), which indicates that macrophage activation and COX-2 inhibition are possibly regulated by independent mechanisms. In vivo, our findings presented increased cellularity, blood vessels, and the number of mast cells. However, downregulation was observed in the COX-2 and PGE2 expression, which was limited to epidermal cells. Our results also showed that the downregulation of this pathway benefits the oxidative balance by reducing protein carbonyls, malondialdehyde, nitric oxide, and hydrogen peroxide (H2O2). In addition, there was an increase in the antioxidant enzymes (catalase and superoxide dismutase) after Dx exposure, which demonstrates its antioxidant potential. Finally, Dx increased the number of types I collagen and elastic fibers and reduced the levels of MMP, thus accelerating the closure of skin wounds. Our findings indicated that both doses of Dx can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.


2015 ◽  
Vol 4 (4) ◽  
pp. 197-201
Author(s):  
Tetiana A. Krupodorova ◽  
◽  
Pavlo P. Klymenko ◽  
Victor Yu. Barshteyn ◽  
Yuri I. Leonov ◽  
...  

The aqueous extracts of Ganoderma lucidum 1900 (Curtis) P. Karst and Crinipellis schevczenkovi 31 Buchalo mycelia were investigated for skin wound healing activity in vivo using the excision wound healing model. The extracts were prepared by mixing of 100 mg of powdered mycelium of both mushrooms with 1 mL of sterile distilled water for injections. White albino mice line FVB/Cg., 3 months of age (male), were used for the study. The rate of wound healing and the histology of healed wounds in mice have been studied. Visual method of wound study and histological investigation of skin tissue showed the presence of wound healing potential of G. lucidum and C. schevczenkovi mycelia. The wound healing process was expressed more active on 3th day in case of topical application of C. schevczenkovi mycelium extract, but on 5th day the wound healing effects of both mushroom extracts were almost at the same level and statistically better then results in the control group. Wounds treated with mycelial extracts were covered completely on the 6th day compared with 8th day in control group. Wound healing ability of C. schevczenkovi observed in present investigations for the first time.


2012 ◽  
pp. 241-250 ◽  
Author(s):  
P. GÁL ◽  
T. VASILENKO ◽  
I. KOVÁČ ◽  
M. KOSTELNÍKOVÁ ◽  
J. JAKUBČO ◽  
...  

Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male Sprague-Dawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action.


2021 ◽  
Vol 9 (3) ◽  
pp. 55
Author(s):  
Eberhard Grambow ◽  
Heiko Sorg ◽  
Christian G. G. Sorg ◽  
Daniel Strüder

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Huiling Sun ◽  
Ying Wang ◽  
Tiantian He ◽  
Dingwei He ◽  
Yan Hu ◽  
...  

Abstract Background Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated. Results In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine. Conclusions HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing. Graphic Abstract


2019 ◽  
Vol 20 (10) ◽  
pp. 2579 ◽  
Author(s):  
Chang-Chih Chen ◽  
Chia-Jen Nien ◽  
Lih-Geeng Chen ◽  
Kuen-Yu Huang ◽  
Wei-Jen Chang ◽  
...  

Sapindus mukorossi seed oil is commonly used as a source for biodiesel fuel. Its phytochemical composition is similar to the extracted oil from Sapindus trifoliatus seeds, which exhibit beneficial effects for skin wound healing. Since S. mukorossi seed shows no cyanogenic property, it could be a potential candidate for the treatment of skin wounds. Thus, we evaluated the effectiveness of S. mukorossi seed oil in the treatment of skin wounds. We characterized and quantified the fatty acids and unsaponifiable fractions (including β-sitosterol and δ-tocopherol) contained in S. mukorossi seed-extracted oil by GC-MS and HPLC, respectively. Cell proliferation and migratory ability were evaluated by cell viability and scratch experiments using CCD-966SK cells treated with S. mukorossi oil. The anti-inflammatory effects of the oil were evaluated by measuring the nitric oxide (NO) production in lipopolysaccharide-treated RAW 264.7 cells. Antimicrobial activity tests were performed with Propionibacterium acnes, Staphylococcus aureus, and Candida albicans using a modified Japanese Industrial Standard procedure. Uniform artificial wounds were created on the dorsum of rats. The wounds were treated with a carboxymethyl cellulose (CMC)/hyaluronic acid (HA)/sodium alginate (SA) hydrogel for releasing the S. mukorossi seed oil. The wound sizes were measured photographically for 12 days and were compared to wounds covered with analogous membranes containing a saline solution. Our results showed that the S. mukorossi seed oil used in this study contains abundant monounsaturated fatty acids, β-sitosterol, and δ-tocopherol. In the in vitro tests, S. mukorossi seed oil prompted cell proliferation and migration capability. Additionally, the oil had significant anti-inflammatory and anti-microbial activities. In the in vivo animal experiments, S. mukorossi seed oil-treated wounds revealed acceleration of sequential skin wound healing events after two days of healing. The size of oil-treated wound decreased to half the size of the untreated control after eight days of healing. The results suggest that S. mukorossi seed oil could be a potential source for promoting skin wound healing.


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