The study, published in BMC Plastic and Reconstructive Surgery, included 50 consecutive patients whose wounds were classified as chronic, surgical, or deep second- and third-degree burns. The median age of participants was 50 years, and the population reflected the challenging clinical reality of tertiary outpatient wound care: 56 percent had a history of chronic medical illness such as diabetes mellitus or hypertension, and 48 percent were smokers, both well-known factors that impair tissue repair. Wound types were evenly split between surgical and chronic wounds at 22 percent each, with 12 percent being burn injuries. Wound sizes ranged from 4 to 110 square centimeters, with a median of 20 square centimeters, meaning that many of these lesions were substantial tissue defects rather than minor abrasions.

The treatment protocol itself reflected practical bedside medicine rather than laboratory conditions. The gel was typically initiated once the wound was clinically clean and open rather than immediately after injury, applied once to twice daily depending on severity and clinical judgment. A standardized alternating-day approach was generally followed, with gel application and dressing on the first day followed by open wound exposure on the second, repeated cyclically. Nineteen patients also received negative pressure wound therapy using Vacuum-Assisted Closure at an average setting of 120 mmHg before or during gel treatment, usually for complex or highly exudative wounds that first needed to be converted into a clean open wound bed. The duration of gel application ranged from 7 to 70 days, with a median of roughly three weeks.

The primary endpoint was deliberately designed as a composite: either complete wound healing, defined as 100 percent epithelialization with no drainage sustained for at least two weeks, or a ready-to-graft state characterized by healthy granulation tissue, absence of necrotic material, minimal exudate, and no clinical signs of infection. Median time to reaching this composite endpoint was 21 days. Every one of the six burn wounds in the cohort healed completely, as did 63.6 percent of chronic wounds and 50 percent of surgical wounds, although the differences across wound types did not reach statistical significance. The researchers are careful to note that the small burn subgroup should be interpreted with caution, and that no gel-related adverse events such as dermatitis, allergic reactions, or wound deterioration were documented anywhere in the records.

When the team applied multivariable Cox proportional hazards regression to identify independent predictors of healing, one variable stood out clearly: wound size. After adjusting for age, chronic disease, smoking status, and wound dimensions, larger wounds were associated with a significantly lower hazard of healing over time, with a hazard ratio of 0.97 (95 percent confidence interval 0.95 to 0.99, P = 0.002). Age, chronic comorbidity, and smoking showed no significant independent associations with time to healing in this cohort. The duration of gel use was also statistically associated with the outcome, but the authors explicitly warn against reading this as evidence that longer application is independently therapeutic; treatment duration is a time-dependent variable that naturally extends in slow-healing wounds, a phenomenon of reverse causation and potential immortal time bias that the team flags as hypothesis-generating only.

The mechanistic rationale behind the formulation rests on the complementary biology of its components. Hyaluronic acid, a glycosaminoglycan naturally present in the extracellular matrix, plays multifaceted roles across every phase of wound repair, from hemostasis through inflammation, proliferation, angiogenesis and remodeling. Its effects are molecular-weight dependent, and clinical evidence supports its value: a Cochrane systematic review of randomized controlled trials concluded that hyaluronic acid dressings significantly improve ulcer healing compared with neutral vehicle, with a risk ratio of 2.11. By keeping the wound moist, hyaluronic acid enhances cell migration, supports growth factor activity, and facilitates autolytic debridement, all of which accelerate the regenerative cascade.

Alginate, a natural polymer derived from brown seaweed, brings a different but equally important set of properties, particularly for wounds producing moderate to heavy exudate. Alginate dressings absorb excess fluid while forming a protective gel barrier that maintains moisture balance at the wound interface, preventing the desiccation-induced cellular damage that stalls healing. An updated systematic review and meta-analysis encompassing 42 randomized controlled trials and 2,536 individuals found that alginate dressings significantly reduced healing time by an average of 4.58 days, accelerated granulation tissue formation, and reduced the frequency of dressing changes compared with conventional dressings. The third pillar, antimicrobial enzymes, targets one of the most stubborn obstacles in chronic wound care: biofilm.

Chronic wounds frequently harbor complex polymicrobial biofilm communities, dominated by organisms such as Staphylococcus aureus and Pseudomonas aeruginosa, encased in protective extracellular polymeric matrices that confer up to a thousand-fold increase in antibiotic resistance compared with free-floating bacteria. These biofilms perpetuate inflammation and block progression through the normal healing phases. Proteolytic and antimicrobial enzymes offer a strategy to degrade biofilm structural proteins, improve antimicrobial penetration, and modulate the excessive proteolytic activity that characterizes chronic wound microenvironments. While the Egyptian study did not directly measure microbial burden or biofilm presence, the authors suggest that the strong outcomes observed in chronic wounds are consistent with the enzymes contributing to infection control and wound bed optimization, even though the exact proprietary concentrations of the ingredients were not available to the investigators.

The clinical case series embedded in the study illustrates the breadth of scenarios in which the gel was used. A post-assault crush wound on the ulnar aspect of the hand and forearm, with exposed paratenon, showed progressive granulation and marginal epithelialization under twice-daily dressings. Crushed wounds of the fingers healed completely without grafts or flaps, and a severe open ankle fracture with lacerated toe extensors was optimized for grafting through daily gel application. A dramatic degloving injury of the entire left leg, managed initially with surgical debridement and vacuum therapy, developed healthy granulation tissue after 50 days of combined treatment and became ready for split-thickness skin grafting. Perhaps most striking, a third-degree burn on the forearm achieved complete epithelialization after only five days of daily dressings, healing without any surgical intervention.

The authors and outside observers alike stress that these findings must be framed within the study’s design. As a retrospective, single-center, single-arm analysis without a control group, it cannot establish that the gel, rather than natural healing trajectories, debridement, vacuum therapy, antibiotics, or surgeon expertise, caused the observed outcomes. Records did not capture the total population of wound patients treated during the period, vascular assessment did not routinely include ankle-brachial index measurements, and the composite endpoint merges two clinically distinct outcomes. Still, the investigators argue that real-world evidence of this kind fills a genuine gap, especially in low- and middle-income settings where accessible, easily applied topical agents can meaningfully reduce the need for early surgery, shorten time to definitive closure, and lower treatment costs. The team calls for multicenter, double-blind, randomized controlled trials comparing the gel against standard wound care to determine whether these promising signals hold up under rigorous scrutiny.

Subject of Research: Clinical evaluation of a hyaluronic acid-based topical gel for wound bed preparation and healing in chronic, surgical, and burn wounds

Article Title: Real-world clinical evaluation of Zymalge® gel for optimizing wound bed prior to skin grafting or spontaneous healing: a retrospective single-arm cohort study

Article References: Amin, M. A., Salah, A. E., Farag, R. S., & Elosh, A. M. M. (2026). Real-world clinical evaluation of Zymalge® gel for optimizing wound bed prior to skin grafting or spontaneous healing: a retrospective single-arm cohort study. BMC Plastic and Reconstructive Surgery, 2(1), Article 18. https://doi.org/10.1186/s44452-026-00029-5

Image Credits: AI Generated

DOI: 10.1186/s44452-026-00029-5

Keywords: wound healing, Zymalge gel, hyaluronic acid, alginate dressings, chronic wounds, burn wounds, skin grafting, wound bed preparation, antimicrobial enzymes, biofilm, plastic surgery, retrospective cohort study