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. 2026 Jul 10;14(7):e7901. doi: 10.1097/GOX.0000000000007901

Negative Pressure Wound Therapy Modulates Wound pH and Bacterial Invasion in Pseudomonas aeruginosa–infected Porcine Wounds

Zhirui Li *,†, Chen Chen ‡, Guoqi Wang †,‡,✉
PMCID: PMC13354449  PMID: 42434083

Abstract

Background:

Pseudomonas aeruginosa infection markedly delays wound healing. Negative pressure wound therapy (NPWT) is widely used for infected wounds, but its effects on wound pH and bacterial invasion remain unclear.

Methods:

A porcine model of full-thickness wounds infected with P. aeruginosa was established. Thirty-six wounds in 18 pigs were treated with NPWT or a gauze dressing. On days 1, 5, 9, and 13 after infection, wound pH, bacterial burden, bacterial invasion depth, inflammatory infiltration, neovascularization, and granulation tissue thickness were assessed.

Results:

Compared with the gauze dressing group, NPWT significantly reduced bacterial counts on days 9 and 13 (P < 0.05 and P < 0.001, respectively). From day 5 onward, wound pH was lower in the NPWT group, with values of 7.82 ± 0.18 versus 8.25 ± 0.19 on day 5; 7.50 ± 0.32 versus 8.20 ± 0.25 on day 9; and 7.23 ± 0.19 versus 7.77 ± 0.23 on day 13. NPWT also reduced bacterial invasion depth at all time points (P < 0.05). Superficial neutrophil aggregation was lower after NPWT on days 5, 9, and 13: 35.60 ± 1.95, 22.40 ± 2.41, and 17.20 ± 1.79 versus 45.20 ± 2.17, 32.80 ± 2.39, and 31.20 ± 2.49, respectively; all P < 0.05. NPWT further enhanced neovascularization and granulation tissue thickness.

Conclusions:

NPWT promotes healing of P. aeruginosa–infected wounds by reducing wound alkalinity, limiting bacterial burden and invasion, attenuating superficial inflammation, and enhancing angiogenesis and granulation tissue formation.

Takeaways

Question: How does negative pressure wound therapy (NPWT) influence the wound microenvironment, particularly wound pH, in Pseudomonas aeruginosa–infected wounds?

Findings: In a porcine full-thickness wound infection model, NPWT reduced bacterial burden, limited bacterial invasion depth, and shifted wound pH from a highly alkaline state toward a mildly alkaline environment. These changes were associated with reduced superficial inflammation, enhanced angiogenesis, and increased granulation tissue formation.

Meaning: NPWT promotes healing of P. aeruginosa–infected wounds not only by bacterial clearance but also by regulating the wound physicochemical microenvironment. Modulation of wound pH may represent an important and adjustable therapeutic mechanism underlying NPWT-assisted tissue regeneration.

INTRODUCTION

The process of wound healing represents a complex and dynamic continuum that involves inflammatory responses, proliferative activities, and tissue remodeling. An infection, particularly one that is multidrug resistant, can significantly complicate the situation.1 Infected wounds typically exhibit a reduced likelihood of complete healing, often leading to complications and imposing significant financial burdens on healthcare systems.2–4 This underscores the critical need for effective interventions to promote recovery and inhibit microbial proliferation. Negative pressure wound therapy (NPWT) has emerged as an essential modality, particularly in addressing complex, recalcitrant wounds that are prone to severe infection.5

NPWT applies subatmospheric pressure to the wound bed through a sealed dressing, facilitating the healing process through the removal of surplus exudate, the stimulation of granulation tissue formation, the enhancement of local blood circulation, and the diminution of bacterial colonization.6–9 In the case of infected wounds, it can significantly decrease bacterial load and markedly improve clinical outcomes.10–12

The impact of wound pH on the processes of wound healing and infection management is currently receiving increased research attention. The secretion of organic acids from keratinocytes results in the physiological pH of normal skin ranging between 4.8 and 6.0, with an increase to 6.8 observed at the lower stratum corneum layer.13,14 Bacterial-infected wounds may exhibit a pH level exceeding 7.4, attributable to the alkaline byproducts generated through bacterial metabolism, inflammatory responses, and tissue degradation.15,16 Research has demonstrated that pH variations significantly influence bacterial behavior. For example, Harjai et al17 reported that exposing Pseudomonas aeruginosa biofilms to a pH of 8 resulted in a notable 17% increase in alginate and proteinase production. Similarly, Kaufman et al18 demonstrated that wounds exhibiting a decreased pH level tend to heal more rapidly compared with those in a higher alkaline environment.

Although NPWT is acknowledged to promote healing in contaminated wounds, its specific impact on wound pH remains uncertain, particularly concerning how such alterations in pH might influence the healing process of wounds infected with P. aeruginosa. P. aeruginosa represents a prevalent pathogen in chronic and burn wounds, renowned for its potent ability to form biofilms and its notable resistance to antibiotic treatment, which significantly complicates infection management and wound healing.3,19 Considering the critical role of pH in bacterial proliferation and host cell functionality, we hypothesized that NPWT facilitates the closure of P. aeruginosa–infected wounds by modulating pH levels, thereby establishing conditions conducive to tissue regeneration rather than bacterial persistence.

This research investigates the influence of NPWT on both the pH levels and healing progression of porcine wounds infected with P. aeruginosa. Monitoring wound pH in conjunction with bacterial load and histopathologic characteristics may help elucidate the role of pH variations in NPTW, providing valuable insights for wound care practitioners.

MATERIALS AND METHODS

Ethical Statement

The experimental protocols involving animals were formally authorized by the Medical Ethics Committee of the Chinese PLA General Hospital (Beijing, China), and all procedures adhered strictly to the established guidelines for the ethical care and use of laboratory animals in scientific research. All animal experiments complied with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publications No. 8023, revised 1978).

Animals

Eighteen female Bama miniature pigs (aged 3 to 4 mo, weighing 15 ± 2 kg) were obtained from the Laboratory Animal Center of the Chinese PLA General Hospital. All animals were healthy and had no prior experimental history. They were individually housed under specific pathogen-free conditions with a 12‑hour light/dark cycle, controlled temperature (22 ± 2°C), and relative humidity (45% ± 5%). Food and water were provided ad libitum.

Bacterial Strains and Culture

The P. aeruginosa PAO1 wild-type strain, which contains the gene encoding green fluorescent protein, was provided by the laboratory at the Institute of Disease Control and Prevention in Beijing, China. P. aeruginosa was cultured overnight at 37°C and subsequently subcultured in Luria-Bertani broth (AOBOX Biotechnology Co. Ltd., Beijing, China) at 37°C until reaching the logarithmic growth phase. The cells were then collected via centrifugation at 4°C (5000g) and washed 3 times with phosphate-buffered saline. The optical density was measured at a wavelength of 600 nm, where an optical density of 1.0 corresponded to approximately 1 × 105 colony-forming units (CFU)/mL, as determined by a standard curve.

Wound Protocol and Inoculate Bacteria

Pigs were anesthetized through intramuscular administration of ketamine (30 mg/kg) (Gutian Pharmaceutical Co., Ltd., Fujian, China) combined with midazolam (500 µg/kg) (Nhwa Pharmaceutical Co., Ltd., Jiangsu, China). Each animal’s dorsal region was prepared by cleansing the area, followed by the application of a depilatory agent (Veet, Reckitt Benckiser, China) to eliminate hair. Subsequently, the site was sterilized through double disinfection using povidone and 70% ethanol before being covered with sterile surgical drapes. Two full-thickness circular excisions, each with a diameter of 5 cm, were created on the dorsum, involving the removal of epidermis, dermis, subdermis, and subcutaneous fat. Hemostasis was achieved by applying light pressure with sterile gauze. Each wound received an inoculation of 5 × 107 CFUs of the P. aeruginosa strain, with a total volume of 0.5 mL. After inoculation, wounds were left undisturbed for 24 hours to allow bacterial colonization.

Treatment Protocol

A total of 36 acute P. aeruginosa-infected wounds (2 wounds per pig) were included in the study. Clinical intervention was performed on the subsequent day. The 2 wounds on each pig’s back were randomly assigned to the NPWT group or the control group using a random number table. For the NPWT group, wound care involved the application of a premodified, standardized NPWT dressing manufactured by Wuhan VSD Medical Science & Technology Co., Ltd., located in Wuhan, China. Throughout the study, the NPWT was consistently maintained at a pressure of −125 mm Hg.20 The control group’s wounds were treated using conventional gauze dressings (sterile dry gauze, Zhende Medical Co., Ltd., Zhejiang, China; product code: 8-ply, 10 × 10 cm). During the process of changing the dressing, the animals were placed under anesthesia. The foam dressings were inspected on a daily basis and replaced on days 5, 9, and 13. Before each dressing change, the wound diameter was carefully measured, and a 5-mm biopsy punch was used to extract tissue samples from the wound sites for subsequent examination and analysis. Each biopsy was performed 3 times per wound. On day 13, animals were euthanized via an excessive intravenous administration of ketamine and midazolam.

Bacterial Count and pH Value Measurement

Tissue samples were harvested for bacterial count quantification and pH value assessment at 24 hours postinoculation (day 1) and on days 5, 9, and 13 following bacterial administration. Under sterile conditions, each sample was weighed and completely homogenized. Serial dilutions of the homogenate were prepared in sterile phosphate-buffered saline, ranging from 10−1 and 10−2 to 10−6, and plated on P. aeruginosa Isolation Agar and incubated at 37°C for 24 hours. A standard colony count procedure was performed and subsequently analyzed by a clinical microbiologist. The colony-counting method was done, and the final results were represented as log CFU/wound.21 The tissue specimen was collected after determining the pH level using a pH test pen manufactured by Shanghai Leici Instrument Co., Ltd.

Measurement of Bacterial Invasion Depth

To assess bacterial invasion depth, full-thickness tissue samples (5-mm punch biopsy) were harvested from the central area of each wound. The samples were sectioned into 6-µm-thick slices using a cryostat and subsequently mounted on slides for analysis under an argon confocal laser scanning microscope (Olympus FV1000, Tokyo, Japan). The P. aeruginosa (constitutive expression of green fluorescent protein) exhibited green fluorescence when visualized using the Olympus FV1000. To determine the extent of P. aeruginosa invasion from the tissue boundary to the deepest point, images were captured at a speed of 4 ms/pixel, with measurements conducted by 2 blinded observers. The depths of the bacterial fluorescent signals in the samples were quantified using FV10-ASW 4.1, integrated within the Olympus FV1000 system.

Histological Analysis and Neutrophil Count

Specimens were fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 µm, and stained for analysis. Hematoxylin and Eosin staining and immunohistochemical analysis using CD31 were performed independently to facilitate more in-depth observations. Image-Pro Plus 6.0 software (Media Cybernetics) was used to quantify the surface area and assess the thickness of newly formed granulation tissue associated with neovascularization. Using this method, a total of 15 color photographs (slides) were obtained at 400× magnification. Specifically, 5 color photographs were captured from the superficial layer, which was 1.5 mm thick and in direct contact with the foam. Another 5 color photographs were acquired from the intermediate layer, located between 1.5 and 3 mm beneath the surface. Additionally, 5 color photographs were taken from the deep layer, situated between 3 and 4.5 mm below the surface.22 Two professional pathologists separately analyzed the neutrophil counts and their temporal evolution in individual cases. The neutrophil count for each layer was expressed as the mean value calculated from 5 photographs of the identical layer.

Statistical Analysis

The temporal progression was assessed through a 2-way analysis of variance (ANOVA) with repeated measures. To determine whether a significant difference exists at any specific time points, a Student t test was conducted. The neutrophil count data were subjected to multivariate ANOVA for between-group comparisons at each time point, whereas 1-way ANOVA was used for within-group assessments across the respective cohorts. Although an a priori power analysis was not conducted, a post hoc power calculation based on the effect size of wound pH on day 9 (Cohen d = 2.1) revealed a power greater than 0.85, indicating that the sample size was sufficient to detect significant differences between groups. Statistical analysis of the data was performed using SPSS software and GraphPad Prism, with significant differences being denoted by a P value less than 0.05.

RESULTS

Bacterial Count and Wound Healing

The viable bacterial cell counts of the 2 groups were assessed at different time intervals (Fig. 1). Before treatment (day 1), the bacterial load was 107 CFU/g tissue in both groups. On day 5, the bacterial load in the NPWT group exhibited minimal disparity compared with the control group, although a relatively lower bacterial count was observed in the NPWT group. NPWT demonstrated a substantial reduction in bacterial count on days 9 and 13 when contrasted with the control group (day 9, P < 0.05; day 13, P < 0.001). A statistically significant difference was observed between the groups on days 9 and 13 when comparing wound gaps (P < 0.001) (Figs. 1A, 1B).

Fig. 1.

Fig. 1.

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Wound healing, bacteria load and wound pH. A, Wound healing outcomes at varying time points in the 2 groups. B, Diameter of wounds at varying time points in the 2 groups. C, Bacterial count at varying time points in the 2 groups. D, pH values of wound sites at different time points between the 2 groups. *P < 0.05, ***P < 0.001.

pH Measurement

The pH levels were measured on day 0 before bacterial inoculation, on day 1 before treatment, and on days 5, 9, and 13 (Fig. 1D). No statistically significant differences were observed between the 2 groups on days 0 and 1, respectively (P < 0.05). The pH levels in the gauze dressing group were significantly elevated compared with the NPWT group on days 5, 9, and 13 (day 5, P < 0.05; days 9 and 13, P < 0.01).

The Farthest Extent of Bacterial Infiltration

The intensity of bacterial fluorescent signals in the samples was quantified on day 1 and subsequently on days 5, 9, and 13 (Fig. 2). The infiltration depth in both groups exhibited a continuous decline from days 1 to 13. On days 5, 9, and 13, significant differences were observed between the NPWT group and the control group (day 5, P < 0.05; days 9 and 13, P < 0.01).

Fig. 2.

Fig. 2.

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Depths of the bacterial fluorescent signal between the 2 groups. A, Representative image of depth of bacterial invasion under fluorescence microscopy in the control group. B, Bacterial invasion depth in the 2 groups at different time points. *P < 0.05, **P < 0.01.

Neutrophil Quantification Analysis

Histological analysis of wound biopsies revealed a reduction in neutrophil counts as tissue depth increased. A notably increased accumulation of neutrophils was detected on days 5, 9, and 13 in the superficial layer of wounds treated with gauze dressings compared with those treated with NPWT (all P < 0.001), whereas no significant differences were observed in the intermediate and deep layers (Fig. 3).

Fig. 3.

Fig. 3.

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Neutrophil counts at different tissue levels between the 2 groups. A, Representative image of the superficial layer, intermediate layer and deep layer in the control group. B, Neutrophil counts at different time point in the 2 groups. ***P < 0.001.

Angiogenesis and Granular Formation

The quantification of neovascularization revealed a significantly larger area in the NPWT group compared with the gauze dressing group on days 5, 9, and 13 (day 5, P < 0.05; day 9, P < 0.01; and day 13, P < 0.001) (Fig. 4). Furthermore, the thickness of newly formed granulation tissue in the NPWT group was significantly greater compared with the gauze dressing group on days 5, 9, and 13, with statistical significance at a P value less than 0.001 (Fig. 5).

Fig. 4.

Fig. 4.

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The difference in the area of neovascularization between the 2 groups. A, Representative image of neovascularization of a wound in the experimental group. The magnification is 40×. B, Area of neovascularization in the 2 groups. *P < 0.05, ** P < 0.01, ***P < 0.001.

Fig. 5.

Fig. 5.

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Difference in the thickness of new granulation tissue between the 2 groups. A, Representative image of new granulation of a wound in the experimental group. B, Thickness of new granulation tissue in the 2 groups. ***P < 0.001.

DISCUSSION

This study primarily investigated the therapeutic efficacy and underlying mechanisms of NPWT in managing P. aeruginosa–infected wounds. Our findings demonstrate that NPWT significantly reduces bacterial load, shifts the wound environment from a highly alkaline to a mildly alkaline state, and inhibits bacterial infiltration. Furthermore, it attenuates the severity of inflammatory responses and accelerates granulation tissue formation, consistent with our initial hypothesis. These results are consistent with the observations documented by Lalliss et al10 and Gao et al,11 who highlighted a substantial reduction in P. aeruginosa burden and enhanced wound healing associated with NPWT. Furthermore, they lend credence to the hypothesis that negative pressure suction impedes biofilm formation due to the distinctive microenvironment it establishes.

In contrast to approaches that rely solely on local acidification, such as that described by Kaufman et al,18 NPWT offers additional advantages by simultaneously coordinating exudate removal and mechanical stimulation, with acidification likely contributing as a complementary mechanism. The application of continuous −125 mm Hg negative pressure not only enhances local perfusion and oxygenation but also may promote lactate accumulation within the wound bed. In this animal model, we provide systematic evidence that infected wounds with an initial pH of approximately 8.6 gradually shift toward a mildly alkaline state as bacterial load decreases, inflammation subsides, and tissue regeneration progresses. This extends the research conducted by Harjai et al,17 who demonstrated that alkaline environments promote increased expression of virulence factors in P. aeruginosa. Previous studies have likewise shown that lowering wound pH can facilitate healing while exerting antibacterial effects.23–26 Research on NPWT has revealed its capacity to mitigate periwound edema, eliminate exudate, and reportedly reduce bacterial bioburden in certain cases.27–29 In our earlier investigation, we established that NPWT served as an efficacious therapeutic approach for diminishing virulence factors and biofilm elements within a rabbit ear biofilm infection model.21 Together, these findings suggest that NPWT alters the wound microenvironment through the removal of purulent exudate, microbial toxins, and other detrimental byproducts. Such changes may influence local pH levels and thereby create conditions that are more conducive to tissue repair and less favorable for bacterial persistence.

Histological analysis revealed a markedly attenuated inflammatory response in the superficial layers of NPWT-treated wounds, whereas no significant differences were observed in deeper tissue layers when compared with controls. This observation is consistent with the findings of Power et al,15 who reported that acidic microenvironments may suppress the release of proinflammatory mediators and limit excessive neutrophil recruitment. Excessive inflammation has been shown to impair wound healing and contribute to secondary tissue injury,30,31 suggesting that the localized modulation of inflammation by NPWT may play a beneficial role in promoting tissue repair. Furthermore, CD31 immunohistochemical analysis demonstrated enhanced angiogenesis and increased granulation tissue thickness in the NPWT group compared with the gauze-treated group. These findings suggest that negative pressure promotes angiogenesis and granulation tissue formation through the integration of mechanical stimulation, localized pH modulation, reduced bacterial burden, and coordinated inflammatory regulation. From a theoretical perspective, incorporating wound acid–base homeostasis into host–pathogen interaction models may help explain how NPWT restores balance when bacterial proliferation overwhelms local microchemical gradients. Beyond standard NPWT, NPWT with instillation represents a promising evolution, with meta-analyses showing enhanced clinical outcomes in infected wounds.9 Future studies integrating objective measurement technologies with advanced NPWT modalities may further optimize treatment strategies. Clinically, this approach may represent a promising strategy for achieving broad-spectrum antibacterial effects and facilitating tissue repair, particularly in wounds complicated by drug-resistant bacteria or biofilm formation, with potential implications for antimicrobial stewardship, wound management strategies, and healthcare cost containment.

Integrating advanced objective measurement technologies, such as 3‑dimensional imaging and virtual wound assessment systems,32 into future NPWT research would enhance the objectivity and reproducibility of clinical evaluations, as already demonstrated in breast reconstruction, aesthetics, and wound management.33,34

Several limitations of this study should be acknowledged. Although porcine dorsal skin shares important anatomical similarities with human skin, differences in immune responses, sweat gland density, and wound-healing dynamics may limit direct translational applicability. Only a single negative pressure level (−125 mm Hg) was evaluated, precluding assessment of pressure-dependent effects on pH modulation and microbial behavior. In addition, pH measurements were obtained using contact-based methods, which may not fully capture spatial heterogeneity or allow real-time visualization of pH gradients within the wound bed. Finally, the 13-day observation period did not permit evaluation of scar formation, collagen remodeling, or long-term tissue integrity.

In summary, this study identifies modulation of the wound microenvironment, suppression of bacterial burden, and attenuation of excessive inflammatory responses as key mechanisms through which NPWT facilitates healing in infected wounds. Wound pH emerges as a potentially adjustable therapeutic target within this process. These findings provide mechanistic support for the continued clinical application of NPWT and offer a foundation for the development of precision-based strategies in the management of complex wound infections.

DISCLOSURES

The authors have no financial interest to declare in relation to the content of this article. This research received funding from the National Natural Science Foundation of China (award no. 82302819) and the Youth Independent Innovation Science Fund of PLAGH (award no. 22QNFC111).

ACKNOWLEDGMENTS

The authors thank all the contributors who participated in the work. During the preparation of this work, the authors used Humanize AI to revise the manuscript. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Footnotes

Published online 10 July 2026.

Disclosure statements are at the end of this article, following the correspondence information.

Zhirui Li and Chen contributed equally to this work.

REFERENCES

  • 1.Bowers S, Franco E. Chronic wounds: evaluation and management. Am Fam Physician. 2020;101:159–166 . [PubMed] [Google Scholar]
  • 2.Falcone M, De Angelis B, Pea F, et al. Challenges in the management of chronic wound infections. J Glob Antimicrob Resist. 2021;26:140–147. [DOI] [PubMed] [Google Scholar]
  • 3.Uberoi A, McCready-Vangi A, Grice EA. The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nat Rev Microbiol. 2024;22:507–521. [DOI] [PubMed] [Google Scholar]
  • 4.Gushiken LFS, Beserra FP, Bastos JK, et al. Cutaneous wound healing: an update from physiopathology to current therapies. Life (Basel). 2021;11:665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Normandin S, Safran T, Winocour S, et al. Negative pressure wound therapy: mechanism of action and clinical applications. Semin Plast Surg. 2021;35:164–170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Streubel PN, Stinner DJ, Obremskey WT. Use of negative-pressure wound therapy in orthopaedic trauma. J Am Acad Orthop Surg. 2012;20:564–574. [DOI] [PubMed] [Google Scholar]
  • 7.Gu H, Zhao X, Sun Y, et al. Negative-pressure wound therapy compared with advanced moist wound therapy: a comparative study on healing efficacy in diabetic foot ulcers. Surgery. 2025;180:109098. [DOI] [PubMed] [Google Scholar]
  • 8.Li W, Zheng J. Negative pressure wound therapy for chronic wounds. Ann Plast Surg. 2024;93:S19–S26. [DOI] [PubMed] [Google Scholar]
  • 9.Wang G, Xu H, Xu G, et al. Clinical outcomes of negative pressure wound therapy with instillation vs standard negative pressure wound therapy for wounds: a meta-analysis of randomized controlled trials. Int Wound J. 2023;20:1739–1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Lalliss SJ, Stinner DJ, Waterman SM, et al. Negative pressure wound therapy reduces pseudomonas wound contamination more than Staphylococcus aureus. J Orthop Trauma. 2010;24:598–602. [DOI] [PubMed] [Google Scholar]
  • 11.Gao J, Wang Y, Song J, et al. Negative pressure wound therapy for surgical site infections: a systematic review and meta-analysis. J Adv Nurs. 2021;77:3980–3990. [DOI] [PubMed] [Google Scholar]
  • 12.Wang J, Yang Y, Xing W, et al. Safety and efficacy of negative pressure wound therapy in treating deep surgical site infection after lumbar surgery. Int Orthop. 2022;46:2629–2635. [DOI] [PubMed] [Google Scholar]
  • 13.Guo J, Cao Y, Wu QY, et al. Implications of pH and ionic environment in chronic diabetic wounds: an overlooked perspective. Clin Cosmet Investig Dermatol. 2024;17:2669–2686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Liu YF, Ni PW, Huang Y, et al. Therapeutic strategies for chronic wound infection. Chin J Traumatol. 2022;25:11–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Power G, Moore Z, O’Connor T. Measurement of pH, exudate composition and temperature in wound healing: a systematic review. J Wound Care. 2017;26:381–397. [DOI] [PubMed] [Google Scholar]
  • 16.Seo HS, Lim H, Lim T, et al. Facile and cost-effective fabrication of wearable alpha-naphtholphthalein-based halochromic sensor for wound pH monitoring. Nanotechnology. 2024;35:245502. [DOI] [PubMed] [Google Scholar]
  • 17.Harjai K, Khandwahaa RK, Mittal R, et al. Effect of pH on production of virulence factors by biofilm cells of Pseudomonas aeruginosa. Folia Microbiol (Praha). 2005;50:99–102. [DOI] [PubMed] [Google Scholar]
  • 18.Kaufman T, Eichenlaub EH, Angel MF, et al. Topical acidification promotes healing of experimental deep partial thickness skin burns: a randomized double-blind preliminary study. Burns Incl Therm Inj. 1985;12:84–90. [DOI] [PubMed] [Google Scholar]
  • 19.Toale C, Kelly A, Leahy F, et al. Effect of pseudomonas colonisation on lower limb venous ulcer healing: a systematic review. J Wound Care. 2022;31:186–192. [DOI] [PubMed] [Google Scholar]
  • 20.Sun T, Fang X, Yang T, et al. Comparison of the effects of negative pressure wound therapy and negative pressure wound therapy with instillation on wound healing in a porcine model. Front Surg. 2023;10:1080838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Wang G, Li Z, Song W, et al. Negative pressure wound therapy reduces the motility of Pseudomonas aeruginosa and enhances wound healing in a rabbit ear biofilm infection model. Antonie Van Leeuwenhoek. 2018;111:1557–1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Liu D, Zhang L, Li T, et al. Negative-pressure wound therapy enhances local inflammatory responses in acute infected soft-tissue wound. Cell Biochem Biophys. 2014;70:539–547. [DOI] [PubMed] [Google Scholar]
  • 23.Liu W, Liu S, Sun M, et al. Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus. Acta Biomater. 2024;181:161–175. [DOI] [PubMed] [Google Scholar]
  • 24.Wang Y, Miao F, Bai J, et al. An observational study of the pH value during the healing process of diabetic foot ulcer. J Tissue Viability. 2024;33:208–214. [DOI] [PubMed] [Google Scholar]
  • 25.Ono S, Imai R, Ida Y, et al. Increased wound pH as an indicator of local wound infection in second degree burns. Burns. 2015;41:820–824. [DOI] [PubMed] [Google Scholar]
  • 26.Cui T, Yu J, Wang CF, et al. Micro-gel ensembles for accelerated healing of chronic wound via pH regulation. Adv Sci (Weinh). 2022;9:e2201254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Orgill DP, Manders EK, Sumpio BE, et al. The mechanisms of action of vacuum assisted closure: more to learn. Surgery. 2009;146:40–51. [DOI] [PubMed] [Google Scholar]
  • 28.Guo Q. Comparison and evaluation of negative pressure wound therapy versus standard wound care in the treatment of diabetic foot ulcers. BMC Surg. 2025;25:208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Ludolph I, Fried FW, Kneppe K, et al. Negative pressure wound treatment with computer-controlled irrigation/instillation decreases bacterial load in contaminated wounds and facilitates wound closure. Int Wound J. 2018;15:978–984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Zhao H, Liu Y. Neutrophil extracellular traps induce fibroblast ferroptosis via IRE1α/XBP1-mediated ER stress to impair diabetic wound healing. Free Radic Biol Med. 2025;236:17–27. [DOI] [PubMed] [Google Scholar]
  • 31.Liu Z, Bian X, Luo L, et al. Spatiotemporal single-cell roadmap of human skin wound healing. Cell Stem Cell. 2025;32:479–498.e8. [DOI] [PubMed] [Google Scholar]
  • 32.Guarro G, Cozzani F, Rossini M, et al. Wounds morphologic assessment: application and reproducibility of a virtual measuring system, pilot study. Acta Biomed. 2021;92:e2021227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Harrar H, Myers S, Ghanem AM. Art or science? An evidence-based approach to human facial beauty a quantitative analysis towards an informed clinical aesthetic practice. Aesthetic Plast Surg. 2018;42:137–146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Guarro G, Cozzani F, Rossini M, et al. The modified TIME-H scoring system, a versatile tool in wound management practice: a preliminary report. Acta Biomed. 2021;92:e2021226. [DOI] [PMC free article] [PubMed] [Google Scholar]

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