HOCl vs. Traditional Antiseptics: A Clinical Comparison for Wound Care

The selection of an appropriate wound cleansing and antimicrobial agent is critical for effective wound management, influencing healing rates, infection prevention, and patient outcomes. For decades, traditional antiseptics such as povidone-iodine, chlorhexidine, and hydrogen peroxide have been mainstays in clinical practice. However, increasing awareness of their limitations, particularly their cytotoxicity and potential for delayed healing, has paved the way for advanced alternatives (del Carmen et al., 2022). Hypochlorous acid (HOCl) has emerged as a superior option, offering potent antimicrobial efficacy coupled with an excellent safety profile (Gold et al., 2020). This article provides a clinical comparison of HOCl against traditional antiseptics, highlighting their mechanisms of action, clinical efficacy, and impact on wound healing.

Understanding the Players: Mechanisms of Action

1. Traditional Antiseptics:
   • Povidone-Iodine (PVP-I): Releases free iodine, which oxidizes essential cellular components of microorganisms, including enzymes and proteins, leading to cell death. It has broad-spectrum activity but can be cytotoxic to mammalian cells, particularly fibroblasts, at concentrations required for high efficacy (del Carmen et al., 2022).
   • Chlorhexidine Gluconate (CHG): A cationic biguanide that disrupts microbial cell membranes, leading to leakage of intracellular contents and cell death. It is broad-spectrum and has some residual activity, but can cause skin irritation and allergic reactions. Cytotoxicity is also a concern, as chlorhexidine has been shown to significantly impair fibroblast viability and inhibit cell migration (del Carmen et al., 2022). The underlying mechanisms include disruption of mitochondrial function, increased intracellular calcium, and induction of oxidative stress in human cells (Babich et al., 1995; Giannelli et al., 2024).
   • Hydrogen Peroxide (H₂O₂): An oxidizing agent that releases oxygen upon contact with catalase in tissues. It can provide mechanical debridement due to effervescence and has some antimicrobial effect, but its efficacy is limited by rapid decomposition in the presence of organic debris and can be cytotoxic to healing cells (Herruzo & Herruzo, 2020).
2. Hypochlorous Acid (HOCl):
   • HOCl is a weak acid produced naturally by neutrophils as part of the innate immune response. Its primary mechanism involves being a potent oxidizing agent. However, it differs from other oxidizers such as H₂O₂ in its electrochemical potential and by reacting via a protonated form (HOCl) or charged form (OCl⁻) depending on pH. At physiological pH, it primarily acts as HOCl (Sakarya et al., 2014; Gold et al., 2020).
   • Selective Toxicity: Unlike traditional antiseptics, HOCl exhibits remarkable selective toxicity. It targets microbial cell walls, membranes, proteins, and nucleic acids through oxidation, disrupting vital cellular functions. Crucially, at therapeutic concentrations, it is significantly less cytotoxic to human cells, including fibroblasts and keratinocytes, thereby supporting the wound healing cascade (Gold et al., 2020; Sakarya et al., 2014).

Clinical Efficacy Comparison

Antimicrobial Spectrum and Potency

• HOCl: Demonstrates broad-spectrum activity against Gram-positive and Gram-negative bacteria, fungi, viruses, and spores. Its efficacy is rapid, and it is exceptionally effective at disrupting biofilms, which are a major challenge in chronic and surgical wounds (Sakarya et al., 2014; Herruzo & Herruzo, 2020). One study found that HOCl achieved a 5-log₁⁴ reduction against eight types of germs within 5–10 minutes, even in the presence of biofilm (Herruzo & Herruzo, 2020).
• PVP-I: Broad-spectrum but can be inactivated by organic debris (blood, pus). Its efficacy against biofilms is variable and generally inferior to that of stabilized HOCl preparations (Shukur & Zeiny, 2025).
• CHG: Broad-spectrum but less effective against some viruses and bacterial spores. Potential for resistance development exists with prolonged use.
• H₂O₂: Limited spectrum and efficacy, particularly against anaerobic bacteria and in infected wounds due to rapid degradation upon contact with tissue catalase.

Biofilm Disruption

• HOCl: Highly effective at penetrating and disrupting the extracellular polymeric substance (EPS) matrix of biofilms, exposing and killing the embedded microorganisms (Robson, 2014; Sakarya et al., 2014). Research using a Staphylococcus aureus biofilm model demonstrated that a 1-minute exposure to HOCl produced greater than 5-log₁⁴ CFU/cm³ reduction, effectively removing the biofilm matrix (Robson, 2014).
• PVP-I & CHG: Limited efficacy against mature biofilms. They often require physical debridement alongside chemical application to achieve meaningful biofilm reduction (Herruzo et al., 2023).
• H₂O₂: Largely ineffective against established biofilms due to rapid decomposition.

Cytotoxicity and Impact on Healing

• HOCl: Low cytotoxicity. Studies show it promotes fibroblast proliferation and migration, which are essential for wound healing (Gold et al., 2020). Minimal impact on granulation tissue formation has been observed across multiple wound types (Sakarya et al., 2014).
• PVP-I: Significantly cytotoxic. In vitro studies demonstrate that povidone-iodine significantly reduces fibroblast cell viability and inhibits cell migration, which can impede granulation tissue formation and delay healing, especially with frequent or prolonged exposure (del Carmen et al., 2022).
• CHG: Cytotoxic. Chlorhexidine digluconate significantly reduces the viability of keratinocytes and inhibits cell migration (del Carmen et al., 2022). It impairs fibroblast function and can delay wound healing at clinically used concentrations (Giannelli et al., 2024).
• H₂O₂: Cytotoxic. Damages fibroblasts and keratinocytes through oxidative stress, hindering wound repair.

Safety and Tolerability

• HOCl: Non-irritating, non-sensitizing, and suitable for use on all wound types, including delicate tissues. No known resistance development has been reported (Gold et al., 2020).
• PVP-I: Can cause skin staining, irritation, and allergic reactions. Potential for thyroid dysfunction with systemic absorption in large or highly absorptive wounds.
• CHG: Can cause skin irritation, allergic contact dermatitis, and rarely, anaphylaxis. It is not recommended for use in body cavities or on sensitive tissues such as the eyes due to the risk of keratitis (Steinsapir & Woodward, 2017; Gold et al., 2020).
• H₂O₂: Can cause tissue damage and discomfort. The foam action can be irritating to periwound skin.

Evidence-Based Recommendations

Clinical guidelines and a growing body of research increasingly favor HOCl for wound irrigation and cleansing.

• The European Wound Management Association (EWMA) guidelines acknowledge the benefits of HOCl in wound cleansing and management, particularly for its antimicrobial properties and favorable safety profile.
• A randomized controlled trial published in Acta Dermato-Venereologica demonstrated that stabilized HOCl irrigation produced immediate and durable antimicrobial action along with significantly improved re-epithelialization in acute wounds compared to controls (Ågren & Eriksen, 2022).
• A large-scale nonrandomized concurrent treatment study of 346 chronic ulcers found that combined HOCl therapy (liquid followed by gel) had a synergistic effect, increasing the probability of complete healing fourfold and reducing infection risk fivefold compared to other antiseptics including chlorhexidine and polyhexanide (Herruzo et al., 2023).
• A direct comparative study of HOCl versus povidone-iodine for infected diabetic foot ulcers confirmed that HOCl produced superior antimicrobial activity, greater reductions in mean ulcer area, and a higher percentage of granulation tissue, resulting in accelerated wound healing (Shukur & Zeiny, 2025).

When to Choose Which Agent

• Choose HOCl for:
  • Routine wound cleansing of acute and chronic wounds.
  • Wounds with signs of infection or high bacterial load.
  • Management of wounds contaminated with biofilms.
  • Surgical site irrigation.
  • Wounds with sensitive periwound skin or fragile granulation tissue.
  • Patients with sensitivities to traditional antiseptics.
• Consider Traditional Antiseptics with Caution for:
  • PVP-I: May be used for pre-operative skin preparation or in specific critical infections under strict clinical orders where its benefits outweigh its risks.
  • CHG: Primarily used for pre-operative skin preparation or hand hygiene; limited role in chronic or open wound irrigation due to its cytotoxicity profile (del Carmen et al., 2022).
  • H₂O₂: Limited use, potentially for mechanical debridement of very superficial, non-infected wounds where effervescence is desired, but generally avoided for deeper wounds or those requiring sustained healing.

Conclusion

While traditional antiseptics have served clinical needs for decades, their well-documented cytotoxic effects and variable efficacy against biofilms present significant limitations in modern wound care (del Carmen et al., 2022; Herruzo et al., 2023). Hypochlorous acid (HOCl) represents a paradigm shift, combining potent, broad-spectrum antimicrobial and antibiofilm activity with low cytotoxicity and excellent tolerability (Gold et al., 2020; Sakarya et al., 2014). Its ability to effectively combat bacteria and biofilms while supporting natural healing mechanisms makes it the preferred choice for wound irrigation and cleansing. Healthcare professionals are encouraged to integrate evidence-based recommendations for HOCl into their wound care protocols for improved patient outcomes. Visit our wound-care and skin-treatment pages for more information.

Frequently Asked Questions (FAQ)

Q1: What is Hypochlorous Acid (HOCl) and how does it work?

A1: HOCl is a natural antimicrobial compound produced by the body’s immune cells (neutrophils) during the oxidative burst response. It works by oxidizing essential microbial components such as cell walls, membranes, proteins, and nucleic acids, effectively killing bacteria, viruses, fungi, and disrupting biofilms, all while remaining gentle on human cells at therapeutic concentrations (Gold et al., 2020; Sakarya et al., 2014).

Q2: How does HOCl compare to Povidone-Iodine (PVP-I) in wound care?

A2: HOCl is generally considered superior for wound irrigation as it is less cytotoxic than PVP-I, meaning it causes less damage to healing cells, allows for better proliferation of fibroblasts, and is more effective against biofilms (Shukur & Zeiny, 2025; del Carmen et al., 2022).

Q3: Are Chlorhexidine or Hydrogen Peroxide suitable for routine wound irrigation?

A3: No, both chlorhexidine and hydrogen peroxide are cytotoxic and can impair wound healing. Clinical evidence shows they damage fibroblasts and keratinocytes, inhibit cell migration, and should generally not be used for routine irrigation of chronic or surgical wounds (del Carmen et al., 2022; Giannelli et al., 2024).

Q4: Can HOCl be used on infected wounds or wounds with biofilms?

A4: Yes, HOCl is highly effective against a broad spectrum of microorganisms and is particularly adept at disrupting and eradicating biofilms. Studies have demonstrated complete removal of biofilm matrices after brief exposure times (Robson, 2014; Herruzo et al., 2023).

Q5: Is HOCl safe for all types of wounds, including surgical and delicate ones?

A5: Yes, HOCl’s low cytotoxicity and non-irritating properties make it safe and suitable for use on all wound types, including surgical incisions, chronic ulcers, and wounds involving delicate tissues (Gold et al., 2020).

Q6: What is the main advantage of HOCl over traditional antiseptics?

A6: The primary advantage is HOCl’s ability to provide potent antimicrobial action and biofilm disruption without the significant cytotoxicity associated with traditional antiseptics, thus supporting and promoting the wound healing process (Sakarya et al., 2014; Gold et al., 2020).

References

Ågren, M. S., & Eriksen, J. H. (2022). Effect of stabilized hypochlorous acid on re-epithelialization and bacterial bioburden in acute wounds: A randomized controlled trial in healthy volunteers. Acta Dermato-Venereologica, 102, adv00727. https://doi.org/10.2340/actadv.v102.4426

Babich, H., Wurzburger, B. J., Rubin, Y. L., Sinensky, M. C., & Blau, L. (1995). An in vitro study on the cytotoxicity of chlorhexidine digluconate to human gingival cells. Cell Biology and Toxicology, 11(2), 79–88. https://doi.org/10.1007/BF00757599

del Carmen, D. M., García, M. A., Rodríguez, P. D., & Fernández, G. T. (2022). Cytotoxicity and wound closure evaluation in skin cell lines after treatment with common antiseptics for clinical use. Cells, 11(9), 1395. https://doi.org/10.3390/cells11091395

Giannelli, M., Chellini, F., Margheri, M., Tani, A., & Squecco, R. (2024). Cytotoxicity evaluation of chlorhexidine and Blue®M applied to a human gingival fibroblast (HGF-1) and keratinocytes (NOK-SI). Journal of Stomatology, Oral and Maxillofacial Surgery, 125(5, Suppl. 2), Article 101923. https://doi.org/10.1016/j.jormas.2024.101923

Gold, M. H., Andriessen, A., Bhatia, A. C., Bitter, P., Chilukuri, S., Cohen, J. L., & Robb, C. W. (2020). Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures. Journal of Cosmetic Dermatology, 19(2), 270–277. https://doi.org/10.1111/jocd.13280

Herruzo, R., Fondo Alvarez, E., Herruzo, I., Garrido-Estepa, M., Santiso Casanova, E., & Cerame Perez, S. (2023). Synergistic effect of two formulations of hypochlorous acid in the treatment of 346 chronic ulcers. Wound Repair and Regeneration, 31(3), 401–409. https://doi.org/10.1111/wrr.13079

Herruzo, R., & Herruzo, I. (2020). Antimicrobial efficacy of a very stable hypochlorous acid formula compared with other antiseptics used in treating wounds: In-vitro study on micro-organisms with or without biofilm. Journal of Hospital Infection, 105(2), 289–294. https://doi.org/10.1016/j.jhin.2020.01.013

Robson, M. C. (2014). Treating chronic wounds with hypochlorous acid disrupts biofilm. Today’s Wound Clinic, 8(6), 20–23.

Sakarya, S., Gunay, N., Karakulak, M., Ozturk, B., & Ertugrul, B. (2014). Hypochlorous acid: An ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency. Wounds, 26(12), 342–350.

Shukur, A. A., & Zeiny, S. M. H. (2025). Efficacy of hypochlorous acid solution in comparison with povidone iodine solution for the management of infected diabetic foot ulcers. Medical Journal Armed Forces India. Advance online publication. https://doi.org/10.1016/j.mjafi.2024.11.015

Steinsapir, K. D., & Woodward, J. A. (2017). Chlorhexidine keratitis: Safety of chlorhexidine as a facial antiseptic. Dermatologic Surgery, 43(1), 1–6. https://doi.org/10.1097/DSS.0000000000000822