Bilateral Thermal Keratopathy Due to Plasma Skin Regeneration.

A 40-year-old woman underwent periocular plasma skin regeneration, a cosmetic treatment for periorbital rejuvenation. She subsequently developed bilateral thermal keratitis, manifesting as blurred vision, irritation, and redness, with a vision decrease to 20/60 and 20/50 in her OD and OS, respectively. Examination demonstrated bilateral large, irregular corneal epithelial defects and edema, necessitating treatment with amniotic membrane grafts, bandage contact lenses, and hypertonic saline. One year posttreatment, her visual acuity improved to 20/20 and 20/25, albeit with ongoing symptomatic dryness and bilateral anterior stromal haze. This case, as only the second reported instance of ocular damage from periocular plasma skin regeneration, underscores the need for heightened awareness of potential ocular complications following plasma skin regeneration and reinforces the importance of protective measures during periocular procedures.

In vivo study on the repair of rat Achilles tendon injury treated with non-thermal atmospheric-pressure helium microplasma jet.

Non-thermal atmospheric-pressure plasma (NTAPP) has been widely studied for clinical applications, e.g., disinfection, wound healing, cancer therapy, hemostasis, and bone regeneration. It is being revealed that the physical and chemical actions of plasma have enabled these clinical applications. Based on our previous report regarding plasma-stimulated bone regeneration, this study focused on Achilles tendon repair by NTAPP. This is the first study to reveal that exposure to NTAPP can accelerate Achilles tendon repair using a well-established Achilles tendon injury rat model. Histological evaluation using the Stoll's and histological scores showed a significant improvement at 2 and 4 weeks, with type I collagen content being substantial at the early time point of 2 weeks post-surgery. Notably, the replacement of type III collagen with type I collagen occurred more frequently in the plasma-treated groups at the early stage of repair. Tensile strength test results showed that the maximum breaking strength in the plasma-treated group at two weeks was significantly higher than that in the untreated group. Overall, our results indicate that a single event of NTAPP treatment during the surgery can contribute to an early recovery of an injured tendon.

Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma.

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures.

How does atmospheric pressure cold helium plasma affect the biomechanical behaviour on alkali-lesioned corneas?

BACKGROUND: Melting corneal ulcers are a serious condition that affects a great number of animals and people around the world and it is characterised by a progressive weakening of the tissue leading to possible severe ophthalmic complications, such as visual impairment or blindness. This disease is routinely treated with medical therapy and keratoplasty, and recently also with alternative regenerative therapies, such as cross-linking, amniotic membrane transplant, and laser. Plasma medicine is another recent example of regenerative treatment that showed promising results in reducing the microbial load of corneal tissue together with maintaining its cellular vitality. Since the effect of helium plasma application on corneal mechanical viscoelasticity has not yet been investigated, the aim of this study is first to evaluate it on ex vivo porcine corneas for different exposition times and then to compare the results with previous data on cross-linking treatment. RESULTS: 94 ex vivo porcine corneas divided into 16 populations (healthy or injured, fresh or cultured and treated or not with plasma or cross-linking) were analysed. For each population, a biomechanical analysis was performed by uniaxial stress-relaxation tests, and a statistical analysis was carried out considering the characteristic mechanical parameters. In terms of equilibrium normalised stress, no statistically significant difference resulted when the healthy corneas were compared with lesioned plasma-treated ones, independently of treatment time, contrary to what was obtained about the cross-linking treated corneas which exhibited more intense relaxation phenomena. CONCLUSIONS: In this study, the influence of the Helium plasma treatment was observed on the viscoelasticity of porcine corneas ex vivo, by restoring in lesioned tissue a degree of relaxation similar to the one of the native tissue, even after only 2 min of application. Therefore, the obtained results suggest that plasma treatment is a promising new regenerative ophthalmic therapy for melting corneal ulcers, laying the groundwork for further studies to correlate the mechanical findings with corneal histology and ultrastructural anatomy after plasma treatment.

Novel Nonthermal Atmospheric Plasma Irradiation of Titanium Implants Promotes Osteogenic Effect in Osteoporotic Conditions.

Osteoporosis is a metabolic disease characterized by bone density and trabecular bone loss. Bone loss may affect dental implant osseointegration in patients with osteoporosis. To promote implant osseointegration in osteoporotic patients, we further used a nonthermal atmospheric plasma (NTAP) treatment device previously developed by our research group. After the titanium implant (Ti) is placed into the device, the working gas flow and the electrode switches are turned on, and the treatment is completed in 30 s. Previous studies showed that this NTAP device can remove carbon contamination from the implant surface, increase the hydroxyl groups, and improve its wettability to promote osseointegration in normal conditions. In this study, we demonstrated the tremendous osteogenic enhancement effect of NTAP-Ti in osteoporotic conditions in rats for the first time. Compared to Ti, the proliferative potential of osteoporotic bone marrow mesenchymal stem cells on NTAP-Ti increased by 180% at 1 day (P = 0.004), while their osteogenic differentiation increased by 149% at 14 days (P < 0.001). In addition, the results indicated that NTAP-Ti significantly improved osseointegration in osteoporotic rats in vivo. Compared to the Ti, the bone volume fraction (BV/TV) and trabecular number (Tb.N) values of NTAP-Ti in osteoporotic rats, respectively, increased by 18% (P < 0.001) and 25% (P = 0.007) at 6 weeks and the trabecular separation (Tb.Sp) value decreased by 26% (P = 0.02) at 6 weeks. In conclusion, this study proved a novel NTAP irradiation titanium implant that can significantly promote osseointegration in osteoporotic conditions.

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study.

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

Cold atmospheric plasma is bactericidal to wound-relevant pathogens and is compatible with burn wound healing.

Burn wound healing can be significantly delayed by infection leading to increased morbidity and hypertrophic scarring. An optimal antimicrobial agent would have the ability to kill bacteria without negatively affecting the host skin cells that are required for healing. Currently available products provide antimicrobial coverage, but may also cause reductions in cell proliferation and migration. Cold atmospheric plasma is a partially ionized gas that can be produced under atmospheric pressure at room temperature. In this study a novel handheld Aceso Plasma Generator was used to produce and test Aceso Cold Plasma (ACP) in vitro and in vivo. ACP showed a potent ability to eliminate bacterial load in vitro for a number of different species. Deep partial-thickness and full-thickness wounds that were treated with ACP after burning, after excision, after autografting, and at days 5, 7, and 9 did not show any negative effects on their wound healing trajectories. On par with in vitro analysis, bioburden was decreased in treated wounds vs. control. In addition, metrics of hypertrophic scar such as dyschromia, elasticity, trans-epidermal water loss (TEWL), and epidermal and dermal thickness were the same between the two treatment groups.It is likely that ACP can be used to mitigate the risk of bacterial infection during the phase of acute burn injury while patients await surgery for definitive closure. It may also be useful in treating wounds with delayed re-epithelialization that are at risk for infection and hypertrophic scarring. A handheld cold plasma device will be useful in treating all manner of wounds and surgical sites in order to decrease bacterial burden in an efficient and highly effective manner without compromising wound healing.

No-ozone cold plasma induces apoptosis in human neuroblastoma cell line via increased intracellular reactive oxygen species (ROS).

BACKGROUND: This study aimed to evaluate the effect of argon-based No-ozone Cold Plasma (NCP) on neuroblastoma cancer cell apoptosis. METHODS: Experiments were performed with SK-N-SH and HS 68. Cell cultures were treated with NCP for 1, 3, and 5 min. NCP was applied using three different strategies: direct NCP application to cell cultures, to only media, and to only cells. Evaluation of cell viability and the level of the reactive oxygen species (ROS) was performed. N-acetyl-L-cysteine (NAC) was also used to antagonize intracellular ROS. Cleaved caspase 3, PARP, aquaporin (AQP) 3 and 8 were detected. RESULTS: NCP induced a gradual decrease in the SK-N-SH cell viability. In contrast, the viability of HS 68 cells did not change. SK-N-SH cells viability was reduced the most when the only media-NCP application strategy was employed. Intracellular ROS levels were significantly increased with time. Cleaved caspase 3 and PARP were increased at 6 h after NCP application. SK-N-SH cells remained viable with NAC after NCP application. AQP 3 and 8 were over-expressed in SK-N-SH cells. CONCLUSION: These findings demonstrate the anti-cancer effect of NCP on neuroblastoma cells. NCP enhanced the selective apoptosis of neuroblastoma cells due to the increased intracellular ROS.

Cold atmospheric plasma sensitizes head and neck cancer to chemotherapy and immune checkpoint blockade therapy.

Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAPPZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addition, we endeavored to examine the efficacy of combining CAPPZ2 with chemotherapy drugs (i.e., cisplatin) or immune checkpoint blockade (ICB, i.e., PD1 antibody) in HNC treatment. Firstly, the results demonstrated that CAPPZ2 exerted anti-neoplastic functions through inhibiting cell proliferation, migration and invasion, and promoting apoptosis and autophagy. Secondly, using transcriptomic sequencing, Western blotting, and quantitative real-time PCR, the mechanisms underlying CAPPZ2 treatment in vitro was presumed to be a multitargeted blockade of major cancer survival pathways, such as redox balance, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling. Lastly, combinatorial thearpy containing CAPPZ2 and cisplatin or PD-1 antibody significantly suppressed tumor growth and prolonged recipient survival in vivo. Collectively, the synergistic effects of CAPPZ2 and cisplatin or PD-1 antibody could serve as a promising solution to enhance head and neck tumor elimination.

Cold Atmospheric Pressure Plasma: A Growing Paradigm in Diabetic Wound Healing-Mechanism and Clinical Significance.

Diabetes is one of the most significant causes of death all over the world. This illness, due to abnormal blood glucose levels, leads to impaired wound healing and, as a result, foot ulcers. These ulcers cannot heal quickly in diabetic patients and may finally result in amputation. In recent years, different research has been conducted to heal diabetic foot ulcers: one of them is using cold atmospheric pressure plasma. Nowadays, cold atmospheric pressure plasma is highly regarded in medicine because of its positive effects and lack of side effects. These conditions have caused plasma to be considered a promising technology in medicine and especially diabetic wound healing because studies show that it can heal chronic wounds that are resistant to standard treatments. The positive effects of plasma are due to different reactive species, UV radiation, and electromagnetic fields. This work reviews ongoing cold atmospheric pressure plasma improvements in diabetic wound healing. It shows that plasma can be a promising tool in treating chronic wounds, including ones resulting from diabetes.

A novel approach to expedite wound healing with plasma brush of cold flame.

Excessive or persistent infection is a major contributing factor in impeding chronic wound healing. Wound bed preparations using antiseptics do not necessarily target the entire bacterial spectrum, and the highly proliferating granulation tissue may be sensitive to the cytotoxic effects, impairing tissue repair. Non-thermal gas atmospheric pressure plasmas are partially ionized gases that contain highly reactive particles while the gas phase remains near room temperature, thus having the capability of accessing small irregular cavities and fissures and killing bacteria because of the diffusive nature of gas phase plasma species that are chemically reactive, providing an ideal approach to topical wound disinfection. A non-thermal plasma brush device of novel design has been developed that is suitable for clinical application in the disinfection of oral and wound bacteria. In vivo studies have indicated that the plasma brush treatment rendered no harmful effect on healthy skin or tissues, while it could improve wound healing in Pseudomonas aeruginosa biofilm infected wounds exposed to an optimized treatment with argon plus 1% nitrogen (Ar + N2) plasma.

Cold atmospheric plasma induces the curing mechanism of diabetic wounds by regulating the oxidative stress mediators iNOS and NO, the pyroptotic mediators NLRP-3, Caspase-1 and IL-1ß and the angiogenesis mediators VEGF and Ang-1.

It has been demonstrated that cold atmospheric plasma (CAP) accelerates the wound healing process, however the underlying molecular pathways behind this effect remain unclear. Thus, the goal of the proposed investigation is to elucidate the therapeutic advantages of CAP on angiogenesis, pyroptotic, oxidative stress, and inflammatory mediators during the wound-healing mechanisms associated with diabetes. Intraperitoneal administration of streptozotocin (STZ, 60 mg/Kg) of body weight was used to induce type-1 diabetes. Seventy-five male mice were randomized into 3 groups: the control non-diabetic group, the diabetic group that was not treated, and the diabetic group that was treated with CAP. The key mediators of pyroptosis and its impact on the slow healing process of diabetic wounds were examined using histological investigations employing H&E staining, immunohistochemistry, ELISA, and Western blotting analysis. Angiogenesis proteins (VEGF, Ang-1, and HO-1) showed a significant decline in expression concentrations in the diabetic wounds, indicating that diabetic animals' wounds were less likely to heal. Furthermore, compared to the controls, the major mediators of pyroptosis (NLRP-3, IL-1ß, and caspase-1), oxidative stress (iNOS and NO), and inflammation (TNF-α and IL-6) have higher expression levels in the diabetic wounds. These factors substantially impede the healing mechanism of diabetic wounds. Interestingly, our results disclosed the therapeutic impacts of CAP treatment in the healing process of diabetic wounds via significantly regulating the expression levels of angiogenesis, pyroptosis, oxidative stress and pro-inflammatory mediators. Our findings demonstrated the curative likelihood of CAP and the underlying mechanisms for enhancing the healing process of diabetic wounds.

Cold plasma-treated medium preferentially eliminates doxorubicin-resistant osteosarcoma cells.

Osteosarcoma (OS) is an aggressive bone cancer with poor prognosis, largely due to the limited effectiveness of current treatments such as doxorubicin (DX). Developing ways to overcome DX resistance is a significant clinical challenge. Here, we used two DX-resistant models to study the potential of Cold Plasma Treated Medium (PTM) to prevent DX resistance in OS. During the acquisition of the resistant phenotype upon long-term DX exposure, OS resistant cells became less proliferative, overexpressed the drug resistance-related efflux pump MDR1 and displayed a concomitant loss of SOD2 or GPX1. According to the reduced expression of these antioxidant enzymes, PTM treatment produced higher levels of oxidative express and was more effective in eradicating DX-resistant cells. Moreover, PTM reduced the expression of MDR1, thus sensitizing resistant cells to DX. These findings uncover new vulnerabilities of DX-resistant cells related with their inability to cope with excessive oxidative stress and their dependence on MDR1 that can be exploited using PTM-based treatments to provide new therapeutic approaches for the management of drug resistance in OS.

Effect of cold atmospheric plasma/NO gas application with different exposure times on healing in wounds with tissue loss in diabetic rats.

Applications of cold atmospheric plasma/nitric oxide (CAP/NO) gas have recently garnered popularity when treating impaired wound healing in patients with diabetes. In this study, we aimed to investigate the effects of NO gas application for 60 and 120 s on wound healing in diabetic rats. A dorsal excision 3 cm in diameter was performed in 15 diabetic rats; these rats were categorized into the following 3 groups: DC (untreated diabetic control); DNO/60 (exposure to 200 ppm NO gas for 60 s/day); and DNO/120 (exposure to 200 ppm NO gas for 120 s/day). Wound contraction on days 0, 3, 7, 11, and 14 and wound contraction rate between days 0 and 14 were evaluated. On day 14, tissue samples were collected for histopathologic assessment of inflammation, epithelial regeneration, angiogenesis congestion, and collagen fiber organization. Normality of distribution was assessed using the Shapiro-Wilk test, and intergroup comparisons were performed using the Mann-Whitney U test (NPar Test) and the Kruskal-Wallis test (non-parametric ANOVA). Wound contraction during treatment days 7-14 was significantly greater in the NO-treatment groups than in the DC group (p<0.05). The NO60 s and NO120 s groups showed a significantly higher wound contraction rate than the DC group (p=0.033, p=0.049, respectively). Significant differences were noted between the control and NO groups in terms of inflammation (p<0.05) and between the control group and DNO/60 and DNO/120 groups in terms of collagen organization (p<0.05, p<0.01, respectively). Evaluation of epithelialization revealed significant intergroup differences between the control and NO treatment groups (p<0.01). In this study, the application of NO once a day for 60 seconds and 120 seconds in diabetic wounds contributed equally to wound healing.

Positive effects of cold atmospheric plasma on pH in wounds: a pilot study.

OBJECTIVE: Cold atmospheric plasma (CAP) is a promising new option for the treatment of hard-to-heal (chronic) wounds. The aim of this study was to observe the effect of CAP on wound pH, as a correlation between the pH of a wound and its healing tendency has been established in the literature. METHOD: Patients with hard-to-heal wounds were treated with CAP in addition to standard treatment. Treatment was performed with the aid of a small, mobile plasma device, which was used for one minute at a time during dressing changes. The pH value, wound size, and other parameters, such as exudate and signs of infection, were recorded for each treatment. RESULTS: A total of 10 patients took part in the study. During the observation period, there was a significant reduction in pH from a markedly alkaline pH of 9.6 to a neutral pH of 7. This was accompanied by a marked reduction in wound size by an average of 76% with seven applications of CAP within 28 days. The evaluation of tissue granulation, exudate and signs of infection showed a positive trend. CONCLUSION: The number of patients in the present study is not sufficient to prove the relationship between the pH value of the wound and the treatment with CAP. However, there are clear indications that the positive effects of CAP on wound healing, which are recognised in several publications, are also due to its influence on wound pH value.

Cold Atmospheric Plasma: A Promising and Safe Therapeutic Strategy for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Microbial infection, immune system dysfunction, and skin barrier defunctionalization have been regarded as the central events in AD pathogenesis. Cold atmospheric plasma (CAP) is an unbound system composed of many free electrons, ions, and neutral particles, with macroscopic time and spatial scales. Based on dielectric barrier discharge, glow discharge, corona discharge, or arch discharge, CAP is generated at normal atmospheric pressure. Its special physical properties maintain its temperature at 20°C-40°C, combining the advantages of high safety and strong ionic activity. CAP has been tentatively used in inflammatory or pruritic skin disorders such as psoriasis, pruritus, and ichthyosis. Increasing data suggest that CAP can attack the microbial structure due to its unique effects, such as heat, ultraviolet radiation, and free radicals, resulting in its inactivation. Meanwhile, CAP regulates reactive oxygen species and reactive nitrogen species in and out of the cells, thereby improving cell immunocompetence. In addition, CAP has a beneficial effect on the skin barrier function via changing the skin lipid contents and increasing the skin permeability to drugs. This review summarizes the potential effects of CAP on the major pathogenic causes of AD and discusses the safety of CAP application in dermatology in order to expand the clinical application value of CAP to AD.

Non-Thermal Plasma Application in Medicine-Focus on Reactive Species Involvement.

Non-thermal plasma (NTP) application in medicine is a dynamically developing interdisciplinary field. Despite the fact that basics of the plasma phenomenon have been known since the 19th century, growing scientific attention has been paid in recent years to the use of plasma in medicine. Three most important plasma-based effects are pivotal for medical applications: (i) inactivation of a broad spectrum of microorganisms, (ii) stimulation of cell proliferation and angiogenesis with lower plasma treatment intensity, and (iii) inactivation of cells by initialization of cell death with higher plasma intensity. In this review, we explain the underlying chemical processes and reactive species involvement during NTP in human (or animal) tissues, as well as in bacteria inactivation, which leads to sterilization and indirectly supports wound healing. In addition, plasma-mediated modifications of medical surfaces, such as surgical instruments or implants, are described. This review focuses on the existing knowledge on NTP-based in vitro and in vivo studies and highlights potential opportunities for the development of novel therapeutic methods. A full understanding of the NTP mechanisms of action is urgently needed for the further development of modern plasma-based medicine.

Application of cold atmospheric microwave plasma as an adjunct therapy for wound healing in dogs and cats.

BACKGROUND: Cold atmospheric plasma is a novel innovative approach for wound care, and it is currently underrepresented in veterinary medicine. OBJECTIVES: To investigate the efficacy and safety of using cold atmospheric microwave plasma (CAMP) as an adjunct therapy for wound healing in dogs and cats. METHODS: Wound healing outcomes were retrospectively analyzed using clinical records of client-owned dogs and cats who were first managed through standard wound care alone (pre-CAMP period) and subsequently via CAMP therapy (CAMP period). The degree of wound healing was estimated based on wound size and a modified wound scoring system. RESULTS: Of the 27 acute and chronic wounds included in the analysis, 81.48% showed complete healing after the administration of CAMP as an adjunct therapy to standard care. Most wounds achieved complete healing in < 5 weeks. Compared with the pre-CAMP period, the rate of wound healing significantly increased every week in the CAMP period in terms of in wound size (first week, p < 0.001; second week, p = 0.012; third week, p < 0.001) and wound score (first week, p < 0.001; second week, p < 0.001; third week, p = 0.001). No adverse events were noted except for mild discomfort and transient erythema. CONCLUSIONS: CAMP is a well-tolerated therapeutic option with immense potential to support the treatment of wounds of diverse etiology in small animal practice. Further research is warranted to establish specific criteria for CAMP treatment according to wound characteristics.

Generation and measurement of low-temperature plasma for cancer therapy: a historical review.

This review provides a description of the historical background of the development of biological applications of low-temperature plasmas. The generation of plasma, methods and devices, plasma sources, and measurements of plasma properties, such as electron dynamics and chemical species generation in both gaseous and aqueous phases, were assessed. Currently, direct irradiation methods for plasma discharges contacting biological surfaces, such as the skin and teeth, are related to plasma biological interactions. Indirect methods using plasma-treated liquids are based on plasma-liquid interactions. The use of these two methods is rapidly increasing in preclinical studies and cancer therapy. The authors address the prospects for further developments in cancer therapeutic applications by understanding the interactions between the plasma and living organisms.

Injectable cold atmospheric plasma-activated immunotherapeutic hydrogel for enhanced cancer treatment.

Despite the promise of immune checkpoint blockade (ICB) for cancer treatment, challenges associated with this therapy still exist, including low response rates and severe side effects in patients. Here, we report a hydrogel-mediated combination therapy for enhanced ICB therapy. Specifically, cold atmospheric plasma (CAP), an ionized gas consisting of therapeutically effective reactive oxygen species (ROS) and reactive nitrogen species (RNS), can effectively induce cancer immunogenic cell death, releasing tumor-associated antigens in situ and initiating anti-tumor immune responses, which, therefore, can synergistically augment the efficacy of immune checkpoint inhibitors. To minimize the systemic toxicity of immune checkpoint inhibitors and improve the tissue penetration of CAP, an injectable Pluronic hydrogel was employed as a delivery method. Our results show that major long-lived ROS and RNS in CAP can be effectively persevered in Pluronic hydrogel and remain efficacious in inducing cancer immunogenic cell death after intratumoral injection. Our findings suggest that local hydrogel-mediated combination of CAP and ICB treatment can evoke both strong innate and adaptive, local and systemic anti-tumor immune responses, thereby inhibiting both tumor growth and potential metastatic spread.