wound model
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Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 176
Author(s):  
Jun Jiang ◽  
Ursula Kraneburg ◽  
Ulf Dornseifer ◽  
Arndt F. Schilling ◽  
Ektoras Hadjipanayi ◽  
...  

The ability to use the body’s resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research. Here, we tested the effect of topical application of blood-derived hypoxia preconditioned serum (HPS) on wound healing in a murine wound model. Alginate hydrogels loaded with two different HPS concentrations (10 and 40%) were applied topically on full-thickness wounds created on the back of immunocompromised mice. We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Healed tissue samples were investigated on post-operative day 15 (POD 15) by immunohistology and showed an increase in lymphatic vessels (LYVE-1) up to 45% with HPS-40% application, while at this stage, vascularization (CD31) was comparable in the HPS-treated and NT groups. Furthermore, the expression of proliferation marker Ki67 was greater on POD 15 in the NT-group compared to HPS-treated groups, in accordance with the earlier completion of wound healing observed in the latter. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ting-Yung Kuo ◽  
Chao-Cheng Huang ◽  
Shyh-Jou Shieh ◽  
Yu-Bin Wang ◽  
Ming-Jen Lin ◽  
...  

AbstractAn appropriate animal wound model is urgently needed to assess wound dressings, cell therapies, and pharmaceutical agents. Minipig was selected owing to similarities with humans in body size, weight, and physiological status. Different wound sizes (0.07–100 cm2) were created at varying distances but fail to adequately distinguish the efficacy of various interventions. We aimed to resolve potential drawbacks by developing a systematic wound healing system. No significant variations in dorsal wound closure and contraction were observed within the thoracolumbar region between boundaries of both armpits and the paravertebral region above rib tips; therefore, Lanyu pigs appear suitable for constructing a reliable dorsal wound array. Blood flow signals interfered with inter-wound distances ˂ 4 cm; a distance > 4 cm is therefore recommended. Wound sizes ≥ 4 cm × 4 cm allowed optimal differentiation of interventions. Partial- (0.23 cm) and full-thickness (0.6 cm) wounds showed complete re-epithelialization on days 13 and 18 and strongest blood flow signals at days 4 and 11, respectively. Given histological and tensile strength assessments, tissue healing resembling normal skin was observed at least after 6 months. We established some golden standards for minimum wound size and distance between adjacent wounds for effectively differentiating interventions in considering 3R principles.


2021 ◽  
pp. 474-483
Author(s):  
JEEJA PANANCHERY ◽  
Chhaya Gadgoli

The present study is aimed at evaluation of phytosomal gel of the petroleum ether extract of root bark of Onosma echiodes for wound healing activity in rats. Extract of root bark of O. echioides was standardized by isolated naphthoquinone dimer using HPTLC. Phytosomes (equivalent to 2% w/w of naphthoquinones) of the standardized extract were prepared by thin film hydration technique. The wound healing efficacy of the formulation was evaluated in rats by inflicting excision and incision wounds followed by treatment of the wounds topically. The parameters evaluated for healing included determination of breaking strength and tensile strength of healed skin for incision model and percentage wound contraction, hydroxyproline content, granulation tissue free radicals and catalase in excision wound model. The formulation treated group showed a significant healing (p<0.005) of both the excision and incision wounds with respect to wound contraction and tensile strength respectively, as compared to vehicle treated group. The oxidative stress of the granulation tissue was also found to be reduced as indicated by reduced lipid peroxidation and increase in catalase activity. The phytosomal gel of O. echioides effectively exhibited wound healing effect.


2021 ◽  
Author(s):  
Jun Jie Wong ◽  
Kelvin K.L. Chong ◽  
Foo Kiong Ho ◽  
Chee Meng Benjamin Ho ◽  
Ramesh Neelakandan ◽  
...  

Wound infections are often polymicrobial in nature and are associated with poor disease prognoses. Escherichia coli and Staphylococcus aureus are among the top five most cultured pathogens from wound infections. However, little is known about the polymicrobial interactions between E. coli and S. aureus during wound infections. In this study, we show that E. coli kills S. aureus both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. We also show that the BarA-UvrY two component system (TCS) is a novel regulator of the pks island, which acts through the carbon storage global regulatory (Csr) system. Together, our data demonstrate the role of colibactin in inter-species competition and show that it is regulated by BarA-UvrY TCS, a previously uncharacterized regulator of the pks island.


2021 ◽  
Vol 281 ◽  
pp. 114527
Author(s):  
Harpreet Kour ◽  
Rajinder Raina ◽  
Pawan Kumar Verma ◽  
Adil Mehraj Khan ◽  
Makhmoor Ahmad Bhat ◽  
...  

2021 ◽  
Author(s):  
Siyuan Yin ◽  
Jiaxu Ma ◽  
Ru Song ◽  
Chunyan Liu ◽  
Guoqi Cao ◽  
...  

Abstract Background: The crucial role of macrophages in the healing of chronic diabetic wounds is widely known, but previous in vitro classification and marker genes of macrophages may not be fully applicable to cells in the microenvironment of chronic wounds. The heterogeneity of macrophages was studied and classified at the single-cell level in a chronic wound model. Results: We performed single-cell sequencing of CD45+ immune cells within the wound edge and obtained 17 clusters of cells, including 4 clusters of macrophages. One of these clusters is a previously undescribed population of macrophages possessing osteoclast gene expression, for which analysis of differential genes revealed possible functions. We also analysed the differences in gene expression between groups of macrophages in the control and diabetic wound groups at different sampling times. Conclusions: we described the differentiation profile of mononuclear macrophages, which has provided an important reference for the study of immune-related mechanisms in diabetic chronic wounds.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojuan Tan ◽  
Xi Cheng ◽  
Mei Hu ◽  
Yifan Zhang ◽  
Aiqun Jia ◽  
...  

AbstractBacterial biofilms formation is one of the major reasons for treatment failure in chronic wound infections. Therefore, diagnostic biomarkers remain the best option for prevention and treatment of chronic wound infections by biofilms. Herein, Pseudomonas aeruginosa PAO1 was used to mimic biofilm development in porcine skin explants wells as ex vivo wound model. The microscopic imaging showed that PAO1 in porcine skin explants wells formed micro-colonies at 24 h, developed mushroom-like structure at 48 h, and at 72 h mushroom-like structure disappeared, remaining a thin bacterial lawn. RNA-seq data analysis revealed that the expression levels of genes involved in the type II hxc secretion system were significantly higher in biofilms than in planktonic cells, especially the expression of lapA encoding alkaline phosphatase. However, the expression levels of genes associated with denitrification pathway were markedly decreased in biofilms, especially the transcription of nirS encoding nitrite reductase to produce nitric oxide (NO). Therefore, their expressions and products were further detected using RT-qPCR and biochemical assays, respectively. The results found that the expression of lapA and alkaline phosphatase activity were induced, but the expression of nirS and intracellular NO were reduced at the whole biofilms cycle. The study indicates that LapA and NO would play an important role for P. aeruginosa biofilm formation in chronic wound infections. LapA would serve as potential target to monitor chronic wound infections by P. aeruginosa biofilms. Inducing NO would be used to treat chronic wound infections due to P. aeruginosa biofilms.


Author(s):  
Başak Büyük ◽  
Cemre Aydeğer ◽  
Yasemen Adalı ◽  
Hüseyin Avni Eroğlu

Background: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated. Methods: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as Control, Fito, Boron and Plu groups. After the applications performed twice a day and lasting 7 days, skin tissues obtained and evaluated histopathological (inflammatory cell infiltration, oedema, and fibroblast proliferation density) and immunohistochemical (TNF-α, EphrinA1, EphrinB1, EphrinB2 and EphB4). Results: Inflammatory cell infiltration score was found to be higher in the Fito group compared to Boron group (p = .018). Fibroblast proliferation density was higher in Plu group than Boron group (p = .012). While TNF-α was lower in boron group than Plu (p = .027) and Fito (p = .016) groups, EphrinA1 was higher in Boron group than Plu group (p = .005). EphrinB1 expression was higher in Boron group compared to Plu (p = .015) and Fito (p = .015) groups, and the same difference was also observed in EphrinB2 (p values .000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to Plu (p = .000) and Fito (p = .002). Conclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.


2021 ◽  
Author(s):  
Xiaojuan Tan ◽  
Xi Cheng ◽  
Mei Hu ◽  
Yifan Zhang ◽  
Aiqun Jia ◽  
...  

Abstract Bacterial biofilms formation is one of the major reasons for treatment failure in chronic wound infections. Therefore, diagnostic biomarkers remain the best option for prevention and treatment of chronic wound infections by biofilms. Herein, Pseudomonas aeruginosa PAO1 was used to mimic biofilm development in porcine skin explants wells as ex vivo wound model. The microscopic imaging showed that PAO1 in porcine skin explants wells formed micro-colonies at 24 h, developed mushroom-like structure at 48 h, and at 72 h mushroom-like structure disappeared, remaining a thin bacterial lawn. RNA-seq data analysis revealed that the expression levels of genes involved in the type II hxc secretion system were significantly higher in biofilms than in planktonic cells, especially the expression of lapA encoding alkaline phosphatase. However, the expression levels of genes associated with denitrification pathway were markedly decreased in biofilms, especially the transcription of nirS encoding nitrite reductase to produce nitric oxide (NO). Therefore, their expressions and products were further detected using RT-qPCR and biochemical assays, respectively. The results found that the expression of lapA and alkaline phosphatase activity were induced, but the expression of nirS and intracellular NO were reduced at the whole biofilms cycle. The study indicates that LapA and NO would play an important role for P. aeruginosa biofilm formation in chronic wound infections. LapA would serve as potential target to monitor chronic wound infections by P. aeruginosa biofilms. Inducing NO would be used to treat chronic wound infections due to P. aeruginosa biofilms.


2021 ◽  
Vol 12 ◽  
Author(s):  
Laryssa C. Manigat ◽  
Mitchell E. Granade ◽  
Suchet Taori ◽  
Charlotte Anne Miller ◽  
Luke R. Vass ◽  
...  

The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint. In fact, the only significant phenotype previously observed in Dgka knockout (KO) mice is the enhancement of T-cell activity. Herein we reveal a novel, macrophage-specific, immune-regulatory function of DGKα. In bone marrow-derived macrophages (BMDMs) cultured from wild-type (WT) and KO mice, we observed increased responsiveness of KO macrophages to diverse stimuli that yield different phenotypes, including LPS, IL-4, and the chemoattractant MCP-1. Knockdown (KD) of Dgka in a murine macrophage cell line resulted in similar increased responsiveness. Demonstrating in vivo relevance, we observed significantly smaller wounds in Dgka-/- mice with full-thickness cutaneous burns, a complex wound healing process in which macrophages play a key role. The burned area also demonstrated increased numbers of macrophages. In a cortical stab wound model, Dgka-/- brains show increased Iba1+ cell numbers at the needle track versus that in WT brains. Taken together, these findings identify a novel immune-regulatory checkpoint function of DGKα in macrophages with potential implications for wound healing, cancer therapy, and other settings.


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