Effects of ALA-PDT on the Healing of Mouse Skin Wounds Infected With Pseudomonas aeruginosa and Its Related Mechanisms

Photodynamic therapy (PDT) is a promising new method to eliminate microbial infection and promote wound healing. Its effectiveness has been confirmed by some studies; however, the mechanisms of PDT in wound healing remain obscure. We used mouse skin wounds infected with Pseudomonas aeruginosa as a research object to explore the therapeutic effects and mechanisms of 5-aminolevulinic acid photodynamic therapy (ALA-PDT). ALA-PDT treatment significantly reduced the load of P. aeruginosa in the wound and surrounding tissues and promoted the healing of skin wounds in mice. Hematoxylin-eosin (HE) and Sirius red staining showed that ALA-PDT promoted granulation tissue formation, angiogenesis, and collagen regeneration and remodeling. After ALA-PDT treatment, the expression of inflammatory factors (TNF-α and IL-1β) first increased and then decreased, while the secretion of growth factors (TGF-β-1 and VEGF) increased gradually after treatment. Furthermore, ALA-PDT affected the polarization state of macrophages, activating and promoting macrophages from an M1 to an M2 phenotype. In conclusion, ALA-PDT can not only kill bacteria but also promote wound healing by regulating inflammatory factors, collagen remodeling and macrophages. This study further clarifies the mechanism of PDT in the healing of infectious skin wounds and provides further experimental evidence for its clinical treatment of skin wounds infected by P. aeruginosa.

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Enhancing wound healing in recalcitrant leg ulcers with aminolevulinic acid-mediated antimicrobial photodynamic therapy

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2020.102149 ◽

2020 ◽

pp. 102149

Author(s):

Ming-Hsien Lin ◽

Julia Yu-Yun Lee ◽

Shin-Chen Pan ◽

Tak-Wah Wong

Keyword(s):

Wound Healing ◽

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Antimicrobial Photodynamic Therapy ◽

Leg Ulcers

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The Role of Porphyrinoid Photosensitizers for Skin Wound Healing

International Journal of Molecular Sciences ◽

10.3390/ijms22084121 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4121

Author(s):

Mariana C. S. Vallejo ◽

Nuno M. M. Moura ◽

Ana T. P. C. Gomes ◽

Ana S. M. Joaquinito ◽

Maria Amparo F. Faustino ◽

...

Keyword(s):

Wound Healing ◽

Aminolevulinic Acid ◽

Healing Process ◽

Protoporphyrin Ix ◽

Skin Wound ◽

Regenerative Process ◽

Inflammatory Factors ◽

Skin Wound Healing ◽

Promising Alternative ◽

Bacteria And Fungi

Microorganisms, usually bacteria and fungi, grow and spread in skin wounds, causing infections. These infections trigger the immune system and cause inflammation and tissue damage within the skin or wound, slowing down the healing process. The use of photodynamic therapy (PDT) to eradicate microorganisms has been regarded as a promising alternative to anti-infective therapies, such as those based on antibiotics, and more recently, is being considered for skin wound-healing, namely for infected wounds. Among the several molecules exploited as photosensitizers (PS), porphyrinoids exhibit suitable features for achieving those goals efficiently. The capability that these macrocycles display to generate reactive oxygen species (ROS) gives a significant contribution to the regenerative process. ROS are responsible for avoiding the development of infections by inactivating microorganisms such as bacteria but also by promoting cell proliferation through the activation of stem cells which regulates inflammatory factors and collagen remodeling. The PS can act solo or combined with several materials, such as polymers, hydrogels, nanotubes, or metal-organic frameworks (MOF), keeping both the microbial photoinactivation and healing/regenerative processes’ effectiveness. This review highlights the developments on the combination of PDT approach and skin wound healing using natural and synthetic porphyrinoids, such as porphyrins, chlorins and phthalocyanines, as PS, as well as the prodrug 5-aminolevulinic acid (5-ALA), the natural precursor of protoporphyrin-IX (PP-IX).

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Therapeutic effects of combined 5-aminolevulinic acid and photodynamic therapy on genital warts and the safety

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.324.9634 ◽

1969 ◽

Vol 32 (4) ◽

Cited By ~ 1

Author(s):

Yine Hu ◽

Shufang Dai ◽

Bin Wang ◽

Wei Qu ◽

Junling Gao

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Genital Warts ◽

Therapeutic Effects

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Topical Application of Cinnamaldehyde Promotes Faster Healing of Skin Wounds Infected with Pseudomonas aeruginosa

Molecules ◽

10.3390/molecules24081627 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1627 ◽

Cited By ~ 6

Author(s):

Thiago A.F. Ferro ◽

Eliene B. Souza ◽

Mariela A.M. Suarez ◽

João F.S. Rodrigues ◽

Domingos M.S. Pereira ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Topical Application ◽

Transient Receptor Potential ◽

Bacterial Load ◽

Unmet Need ◽

Antimicrobial Properties ◽

Mouse Skin ◽

Interleukin 17 ◽

Skin Wounds ◽

Infected Skin

Wound healing can be delayed following colonization and infection with the common bacterium Pseudomonas aeruginosa. While multiple therapies are used for their treatment, these are ineffective, expensive, and labour-intensive. Thus, there is an enormous unmet need for the treatment of infected wounds. Cinnamaldehyde, the major component of cinnamon oil, is well known for its antimicrobial properties. Herein, we investigated the effects of sub-inhibitory concentrations of cinnamaldehyde in the virulence of P. aeruginosa. We also assessed its healing potential in P. aeruginosa-infected mouse skin wounds and the mechanisms involved in this response. Sub-inhibitory concentrations of cinnamaldehyde reduced P. aeruginosa metabolic rate and its ability to form biofilm and to cause haemolysis. Daily topical application of cinnamaldehyde on P. aeruginosa-infected skin wounds reduced tissue bacterial load and promoted faster healing. Lower interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and nitric oxide levels were detected in cinnamaldehyde-treated wound samples. Blockage of transient receptor potential ankyrin 1, the pharmacological target of cinnamaldehyde, abrogated its healing activity and partially reversed the inhibitory actions of this compound on VEGF and IL-17 generation. We suggest that topical application of sub-inhibitory concentrations of cinnamaldehyde may represent an interesting approach to improve the healing of P. aeruginosa-infected skin wounds.

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Efficacy of Topically Delivered Moxifloxacin against Wound Infection by Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01071-10 ◽

2011 ◽

Vol 55 (5) ◽

pp. 2325-2334 ◽

Cited By ~ 34

Author(s):

F. Jacobsen ◽

C. Fisahn ◽

M. Sorkin ◽

I. Thiele ◽

T. Hirsch ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Wound Healing ◽

Wound Infection ◽

High Efficiency ◽

High Morbidity ◽

Methicillin Resistant ◽

Bacterial Counts ◽

Content Type ◽

Promote Wound Healing

ABSTRACTWound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistantStaphylococcus aureus(MRSA) orPseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 105CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.

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Combination of ALA-induced fluorescence-guided resection and intraoperative open photodynamic therapy for recurrent glioblastoma: case series on a promising dual strategy for local tumor control

Journal of Neurosurgery ◽

10.3171/2019.11.jns192443 ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Stephanie Schipmann ◽

Michael Müther ◽

Louise Stögbauer ◽

Sebastian Zimmer ◽

Benjamin Brokinkel ◽

...

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Diffusion Tensor ◽

Case Series ◽

Local Tumor Control ◽

Resection Margins ◽

Tumor Control ◽

Therapeutic Effects ◽

Local Tumor ◽

Continuous Irrigation

OBJECTIVEHigh-grade glioma (HGG) prognosis remains dismal, with inevitable, mostly local recurrence. Regimens for improving local tumor control are therefore needed. Photodynamic therapy (PDT) using porfimer sodium has been investigated but was abandoned due to side effects and lack of survival benefits. Intracellular porphyrins induced by 5-aminolevulinic acid (5-ALA) are approved for fluorescence-guided resections (FGRs), but are also photosensitizers. Activated by light, they generate reactive oxygen species with resultant cytotoxicity. The authors present a combined approach of 5-ALA FGR and PDT.METHODSAfter 5-ALA FGR in recurrent HGG, laser diffusors were strategically positioned inside the resection cavity. PDT was applied for 60 minutes (635 nm, 200 mW/cm diffusor, for 1 hour) under continuous irrigation for maintaining optical clarity and ventilation with 100% oxygen. MRI was performed at 24 hours, 14 days, and every 3 months after surgery, including diffusion tensor imaging and apparent diffusion coefficient maps.RESULTSTwenty patients were treated. One surgical site infection after treatment was noted at 6 months as the only adverse event. MRI revealed cytotoxic edema along resection margins in 16 (80%) of 20 cases, mostly annular around the cavity, corresponding to prior laser diffusor locations (mean volume 3.3 cm3). Edema appeared selective for infiltrated tissue or nonresected enhancing tumor. At the 14-day follow-up, enhancement developed in former regions of edema, in some cases vanishing after 4–5 months. Median progression-free survival (PFS) was 6 months (95% CI 4.8–7.2 months).CONCLUSIONSCombined 5-ALA FGR and PDT provides an innovative and safe method of local tumor control resulting in promising PFS. Further prospective studies are warranted to evaluate long-term therapeutic effects.

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Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02014-w ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jin Liu ◽

Xinyu Qiu ◽

Yajie Lv ◽

Chenxi Zheng ◽

Yan Dong ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Mouse Skin ◽

Skin Wound ◽

Therapeutic Effects ◽

Cutaneous Wound Healing ◽

Apoptotic Bodies ◽

Skin Wound Healing ◽

Cutaneous Wound

Abstract Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

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