Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine
Abstract
:1. Introduction
2. Wound Healing in Animals and Experimental Models
2.1. Rodent Models
2.2. Non-Rodent Models
3. Gas Plasma Treatment of Skin and Wounds in Animal and Veterinary Models
3.1. Murine Models of Gas Plasma in Wound Healing
3.2. Rat and Rabbit Models of Gas Plasma in Wound Healing
3.3. Animal Models of Gas Plasma Treatment of Intact Skin
3.4. Larger Animal Models and Veterinary Patients of Wound Treatment
4. Opportunities of Gas Plasma in Wound Healing Science and Veterinary Medicine
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Animal Model | Discharge Type | Key Outcomes | Ref. |
---|---|---|---|
Wounded | |||
129Sv/Ev | Ar plasma torch system | Elevated FGF-2 production and angiogenesis | [58] |
129Sv/Ev | Ar plasma torch system | Faster wound closure; elevated neutrophil and macrophage levels; higher production of IL-6 and MCP-1; collagen type I production increased | [57] |
Balb/c | He plasma jet or treated liquid | Direct gas plasma exposure did not improve wound healing; gas plasma-treated liquid did not improve healing | [59] |
Balb/c | Ar or He plasma jet | Accelerated wound healing; faster hemostasis | [38] |
Balb/c | He plasma jet | Improved vascularization and angiogenesis | [53] |
Balb/c | Ar plasma jet or treated water | Reduced feed gas flux increased wound temperature; direct gas plasma treatment or exposure to gas plasma-treated water improved wound healing; elevated numbers of myofibroblast | [60] |
Balb/c | Ar plasma jet | Promotion of inflammation, re-epithelization, and wound contraction | [37] |
Balb/c | DBD or Ar or He plasma jet | Ar and He plasma jets showed best wound healing promotion; DBD plasma showed good wound healing promotion | [56] |
Balb/c | He plasma jet | Improved wound healing | [52] |
Balb/c | Ar plasma jet | Wound healing not compared; exposure time-dependent changes of collagen and vimentin | [47] |
Balb/c | Ar plasma jet | Improved wound healing for short but not long exposure times; long treatment showed necrosis and inflammatory cell influx | [45] |
Balb/c | He/O2/N2 plasma jet | Accelerated neovascularization and epithelization; decreased microbial burden of natural wound flora | [54] |
Balb/c | He plasma jet | Skin grafts on wounds exposed to gas plasma elevated angiogenesis and CD31 and hemoglobin expression; increased VEGFR2, PDGFRβ, and eNOS; less TSP-1 expression | [61] |
Balb/c | Ar plasma jet | Short remote but not long direct exposure promoted wound healing and re-epithelization | [46] |
Balb/c | Ar plasma jet + medical honey | Lack of beneficial effect of the combination of gas plasma with hydrocolloid dressings and medical honey | [62] |
Balb/c | Ar plasma jet + medical honey | No improved healing | [63] |
Balb/c | Plasma jet | Infection model; gas plasma jet-to-wound contact reduced infection while remote gas plasma jet treatment was better to stimulate wound healing | [55] |
Balb/c | Hot He plasma jet | This gas plasma jet reached up to 90 °C and hence damaged the skin under various feed gas fluxes and treatment times | [64] |
BKS.CG | He plasma jet | Improved wound closure in diabetic mice with moderate gas plasma treatment; short or long exposure did not improve healing as much | [65] |
C57/BL6 | N2 plasma jet | Wound healing rates dependent on times points investigated; elevated secondary RNS in wound tissue; improved angiogenesis; earlier epithelization and wound contraction | [50] |
C57/BL6 | N2/air plasma jet | Improved wound contraction and healing | [49] |
C57/BL6 | N2/Ar plasma jet | Repeated but not single exposure increased wound healing; elevated blood flow and RNS deposition into tissue; augmented wound strength and laminin production; decreased MMP3 | [51] |
C57/BL6 | Air/He DBD | Treatment of scars two weeks after wounding led to reduction of scar tissue, thickness, and vascularization | [66] |
C57/BL6 | Plasma jet-treated liquid for hydrogels | Gas plasma-treated liquid enriched in hydrogel improved wound healing in random-pattern skin-flap full-thickness wounds | [67] |
C57/BL6 | Ar plasma jet | Improved healing in sterile and infected burn wounds; lower TNFα levels; bacterial burden unchanged | [68] |
db/db | He or He/O2 plasma jet | Faster wound healing in a diabetic model, predominantly in He/0.1% O2 compared to He and He/1% O2 plasma; elevated bFGF and VEGF in all treatment groups investigated | [69] |
ICR | Air DBD-treated water | Improved wound healing; enhanced antimicrobial efficacy; altered wound microbiome | [70] |
ICR | DBD-treated water | Improved wound healing; enhanced pro-inflammatory and anti-inflammatory cytokines and growth factors | [71] |
SKH-1 | Ar plasma jet | Elevated wound tissue oxygenation in deep and superficial layers; enhanced tissue hemoglobin and water index | [39] |
SKH-1 | Ar or Ar/air plasma jet | Best wound closure in and IL-6 mRNA in Ar/Air over Ar plasma | [43] |
SKH-1 | Ar/air plasma jet | Dual-frequency but not single-frequency and 2 but not 1, 3, or 4 gas plasma treatment cycles improved healing; scab hampered gas plasma effects | [44] |
SKH-1 | Ar plasma jet | Improved angiogenesis and wound closure | [36] |
SKH-1 | Ar plasma jet | Lack of adverse events or cancerogenesis one year after repeated gas plasma exposure; improved wound healing | [42] |
SKH-1 | Ar plasma jet | Improved angiogenesis and wound healing; faster re-epithelization; elevated keratin production and collagen fibers; augmented p53 activation, Nrf2 response, macrophage infiltration, inflammation, and granulation | [40] |
SKH-1 | Ar plasma jet | Focal adhesion signaling complexes and junctional protein expression along with EMT and FMT accompanied improved wound healing | [41] |
(not stated) | Ar/O2 plasma-treated oil emulsion | Improved wound closure | [72] |
(not stated) | Ar/air or Ar/O2 plasma jet-treated oil | Accelerated wound healing with oil application previously treated with either air or O2 plasma regimens | [73] |
(not stated) | Plasma jet | Improved wound healing and formation of keratin and granular layers along with collagen and αSMA deposition | [48] |
Non-Wounded | |||
129Sv/Ev | Ar plasma torch | Keratinocyte proliferation, migration, and apoptosis did not change; β-defensins were found upregulated | [74] |
Balb/c | He/O2 plasma jet | Ameliorated morphological manifestation and reduced epidermal proliferation in imiquimod-induced psoriatic lesions | [75] |
Balb/c | Air DBD | Increased NO deposition; lack of inflammation or changes in skin collagen | [76] |
Balb/c | Ar plasma jet | Local treatment through healthy skin in diabetic mice; presumable systemic effects on MDA, AOPP, oxLDL, and cytokines observed | [77] |
Balb/c | Ar/N2/O2/humidity DBD | Allergic contact dermatitis models; humidified argon decreased disease severity greater than N2 or O2 admixture | [78] |
C57/BL6 | N2 plasma jet | Imiquimod-induced psoriasis-like inflammation; reduced epidermal thickness, leukocyte infiltrate, chemokine/cytokine expression (IL-6, IL-17, IL-22, CXCL1, CCL20) | [79] |
CBA | Ar plasma jet | Lack of allergic response in intact skin | [80] |
HRM-2 | Ar plasma jet | E-cadherin decreased; EGF absorption through skin increased | [81] |
HRM-2 | Ar DBD | Enhanced TGF-β, VEGF, GM-CSF, and EGF levels, and epidermal thickness | [82] |
HRS | Ar plasma jet | No dermal degeneration in intact skin; lack of follicular atrophy; elevated catalase and Nrf2 expression | [83] |
KM | Air DBD | Increased lidocaine drug absorption in gas plasma-treated skin; increased permeability was reversible 30 min post-treatment | [84] |
NC/Nga | N2 DBD | Atopic dermatitis-like allergic skin inflammation model; less recruited mast cell and eosinophils; decreased epidermal thickness; less TH2 differentiation | [85] |
SKH-1 | Ar plasma jet | Increased uptake of model drug and tissue oxygenation and microcirculation; changes in lipid composition; changes in junctional protein expression | [86] |
SKH-1 | Plasma jet-treated water | Decrease of symptoms in a model of atopic dermatitis; decreased catalase and increased SOD activity | [87] |
(not stated) | He/Ar/N2/air plasma jet | Psoriasis model; effectiveness in treating psoriasis shown | [88] |
Animal Model | Discharge Type | Key Outcomes | Ref. |
---|---|---|---|
Rats | He plasma jet | In non-diabetic and diabetic rats, improved wound healing, acute inflammation, and neovascularization | [94] |
Sprague Dawley rats | Ar plasma jet | Increased re-epithelization and wound closure; more acute inflammation and less fibrosis | [89] |
Sprague Dawley rats | Ar plasma jet | Faster wound closure in rats as well as Type I and Type II diabetic rats; accelerated re-epithelization and fewer neutrophils; elevated SOD, catalase, and GPx in treated tissues | [90] |
Sprague Dawley rats | Ar plasma jet | Decelerated burn wound injury progression regarding necrosis and neutrophil influx | [91] |
Sprague Dawley rats | He/Ar plasma jet | Improved granulation tissue formation and wound healing; He/Ar better than He plasma; short treatment time better than intermediate and long treatment times | [92] |
Sprague Dawley rats | He plasma jet | Decreased collagen deposition, scar formation, and TGF-β/pSmad2/pSmad3/αSMA positive cells; improved healing | [97] |
Sprague Dawley rats | He plasma jet | Improved wound contraction, healing, and epithelization; unchanged collagen; increased TNFα and IL-1β but not IL-10 | [96] |
Wistar rats | He plasma jet | Improved wound closure, angiogenesis, re-epithelization, inflammation; stronger force resistance; elevated elastic stiffness | [95] |
Wistar rats | He plasma jet | Elevated expression of interleukin-6, nitric oxide synthase 2, prostaglandin-endoperoxide synthase 2 mRNA; decreased expression of nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells and superoxide dismutase 1 mRNA; improved wound closure speed | [93] |
Wistar rats | Ar DBD | Elevated angiogenesis, free thiols, leukocyte influx, and MPO release | [98] |
Wistar rats | Air DBD | Augmented healing of non-infected and infected wounds; elevated angiogenesis and granulation; shortened inflammation | [99] |
Wistar rats | Air DBD | Attenuated long-term inflammation and improved wound healing and collagen I/collagen III ratio | [100] |
Wistar rats | Air DBD | Improved healing in diabetic rats; increased epidermal thickness, re-epithelization, collagen deposition, angiogenesis, proliferation, TGF-β, and fibroblasts counts; decreased T cells | [101] |
Wistar rats | Air DBD-functionalized PEG | Gas plasma-increased adhesion of polypropylene to absorb betaine hydrochloride, which improved wound healing in diabetic rats | [102] |
New Zealand white rabbits | He DBD | Removal of MRSA in infected wounds; modulation of cytokine secretion, inflammation; accelerated re-epithelization and healing | [103] |
New Zealand white rabbits | Air DBD | Lower leukocyte infiltration and decreased viability when investigated early after gas plasma treatment | [104] |
New Zealand white rabbits | Plasma jet | Gas plasma treatment of the skin in diabetic animals was proposed to alter the tender structure in joints | [105] |
Animal Model | Discharge Type | Key Outcomes | Ref. |
---|---|---|---|
Large Animal Models | |||
Bergamasca sheep | He plasma torch | Improved wound healing; lower microbial wound burden; elevated proliferation and VEGF during early wound healing phases | [110] |
Bergamasca sheep | He plasma torch | Improved wound healing efficacy when combined with the application of mesenchymal stem cells | [111] |
Pigs | Ar plasma jet | Both superficial dermal wounds and deep wounds healed well following gas plasma treatment with no side effects; compared to untreated wounds, there were fewer inflammatory (immune) cells in fully healed gas plasma-treated wounds | [9] |
Pigs | Air DBD | Intact skin was damaged with extended exposure times; moderate energy deposition/exposure time did not harm tissue; blood coagulation observed | [112] |
Animal Patients | |||
Dog (case report) | Ar plasma jet | Cutaneous infection with Alternaria spp. was alleviated; cessation of immunosuppressive drugs; complete clinical remission | [113] |
Dogs | Ar plasma jet | Study in 40 dogs with canine bite wounds revealed no superior antimicrobial efficacy of gas plasma; gas plasma exposure was void of side effects | [114] |
Dogs | Ar plasma jet | Study in 85 dogs with canine bite wounds revealed no superior antimicrobial efficacy of gas plasma; gas plasma exposure was void of side effects | [115] |
Dogs and cats | Ar plasma jet | 8 case studies using pets suffering from chronic wounds since 1, 2, 6, 24, 36, 48, 60, and 80 months; complete healing achieved in 7 out of 8 patients | [116,117] |
Dogs, cats, Guinea pigs | Ar plasma jet | 12 case studies using pets suffering from insufficient wound healing; all 12 patients experienced complete remission with repeated gas plasma treatment | [116,118] |
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Bekeschus, S.; Kramer, A.; Schmidt, A. Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine. Molecules 2021, 26, 5682. https://doi.org/10.3390/molecules26185682
Bekeschus S, Kramer A, Schmidt A. Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine. Molecules. 2021; 26(18):5682. https://doi.org/10.3390/molecules26185682
Chicago/Turabian StyleBekeschus, Sander, Axel Kramer, and Anke Schmidt. 2021. "Gas Plasma-Augmented Wound Healing in Animal Models and Veterinary Medicine" Molecules 26, no. 18: 5682. https://doi.org/10.3390/molecules26185682