Immobilization of Bacillus-derived protease onto carboxymethyl chitosan aerogel: A bioactive platform for bacterial inactivation, skin cancer therapy, and accelerated wound healing.

Enzymatic debridement with NexoBrid has become a cornerstone of modern burn care due to its selective tissue-sparing properties. However, the optimal timing and strategy for surgical intervention following enzymatic treatment remain debated. We aimed to evaluate the clinical outcomes of the ENGAGE protocol (ENzymatic debridement with NexoBrid, followed by Grafting After Graded early Excision), a structured algorithm integrating enzymatic debridement with scheduled wound reassessment and selective early excision. This before-and-after observational study included adult patients with burn injuries treated with NexoBrid between January 2020 and October 2025 (2020-2022 received standard NexoBrid management; 2023-2025 received the ENGAGE protocol, featuring day-7 reassessment and selective excision). Endpoints included autologous grafting rate, length of hospital stay (LOS), mortality, and number of surgical procedures. Eighty-eight patients were analyzed (27 standard NexoBrid management, 61 ENGAGE). Baseline characteristics and burn etiologies were comparable. The ENGAGE group showed a significantly shorter LOS (mean ± SD: 24 ± 13.8 vs 32 ± 19.2days, median: 23 vs 27days, P = .03) with no increase in grafting rate (60.7% vs 59.3%, P = .54) or mortality (9.8% vs 7.4%, P > .5). The number of surgical procedures per patient was higher in the ENGAGE group (4.36 ± 3.82 vs 2.74 ± 3.82, P = .029), reflecting planned early reassessment and targeted intervention rather than increased morbidity. The ENGAGE protocol reduces hospital stay without compromising grafting or survival outcomes. By incorporating early, biologically guided excision after enzymatic debridement, it offers a structured and effective refinement of modern burn wound management.

Timely removal of burn eschar is a key determinant of infection control and subsequent wound management in deep burns. Enzymatic debridement using bromelain-based enzymatic debridement enables selective eschar removal; however, the commonly recommended prolonged pre-soaking may delay treatment. Evidence supporting the necessity of extended pre-soaking, particularly in clinically apparent full-thickness burns, remains limited. This single-center, retrospective matched-pair pilot study compared a fast-track enzymatic debridement protocol with short pre-soaking (<4h) to a standard protocol with prolonged pre-soaking (≥4h) in adult patients with deep burns. Seven matched patient pairs (n = 14) were analyzed, matched for age, burn size, depth, and anatomical site. The primary endpoint was timeliness of enzymatic debridement, defined as time from hospital admission to NexoBrid application. Secondary endpoints included debridement adequacy, subsequent wound management, and early safety outcomes. Time from hospital admission to enzymatic debridement was markedly shorter in the fast-track group. Time from injury to enzymatic debridement was also reduced (median 6 vs. 26h). Adequate enzymatic debridement was achieved in all treated wounds in both groups. No wound infections or early safety signals attributable to the fast-track protocol were observed. Fast-track enzymatic debridement using bromelain-based enzymatic debridement, with a median initiation time of 2h and without prolonged pre-soaking, enabled substantially earlier eschar removal without compromising early debridement adequacy or safety in this matched-pair pilot cohort. These findings support the feasibility of a pragmatic, workflow-oriented fast-track approach in selected deep burn wounds and warrant confirmation in prospective studies.

Clinical outcomes of bromelain-based enzymatic debridement (NexoBrid®): evidence from the Italian National Burn Database.

Hand burns, although often limited in surface area, have a major impact on function and quality of life. Debridement-surgical or enzymatic-is a key component of treatment, with enzymatic debridement increasingly used for its selectivity and potential to preserve viable dermis. To evaluate and compare the functional outcomes of hand burns treated with surgical versus enzymatic debridement, using the DASH/Quick-DASH and Michigan Hand Questionnaire (MHQ) assessment tools. A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251034408). Searches were performed in PubMed, Scopus, and Web of Science without date restrictions. Inclusion criteria focused on studies evaluating hand burn function using DASH, Quick-DASH, or MHQ after enzymatic or surgical debridement in patients aged 16 or older. Methodological quality was assessed using the ROBINS-I tool. Of 547 studies identified, 7 met inclusion criteria: 4 surgical and 3 enzymatic. Functional recovery was generally better in cases where enzymatic debridement preserved viable dermis and avoided grafting. DASH and MHQ scores favoured enzymatic approaches, especially when conservative management followed debridement. However, methodological limitations and clinical heterogeneity limited direct comparison. Enzymatic debridement, through preservation of viable dermis and reduced grafting need, appears associated with improved functional outcomes in hand burns. Whilst surgical debridement remains essential for deeper burns, enzymatic methods may offer functional advantages and support early rehabilitation in appropriate cases.

Background: NexoBrid® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.

Deep dermal burns pose a high risk for long-term functional and aesthetic impairments. The choice of wound dressing following enzymatic debridement plays a critical role in modulating the healing response and scar formation. While both Kerecis® and Suprathel® have demonstrated clinical safety and efficacy, comparative long-term data remain limited. Kerecis®, being associated with accelerated wound healing in previous studies, was compared to Suprathel® in this study to evaluate functional and aesthetic scar outcomes using an intraindividual study design. This prospective, intraindividual study included 21 patients with deep dermal burns of the hands and feet, who underwent enzymatic debridement using Nexobrid®. Each patient received treatment with both Kerecis® and Suprathel® on comparable burn areas, ensuring consistency in the comparison. Scar outcomes were evaluated at 3-, 6-, and 12-months post-treatment. Objective parameters such as skin pigmentation, elasticity, transepidermal water loss, and oxygen saturation were measured. Additionally, subjective aesthetic, clinical, and functional parameters were assessed using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). At the 12-months follow-up, objective measurements demonstrated significant differences in erythema and gross elasticity, with Kerecis® exhibiting comparatively favorable outcomes. Subjective analyses indicated a significantly improved scar height and pliability for the Kerecis® group in the VSS and the POSAS Observer Scale. However, no significant differences were found in the POSAS Patient Scale. Both dressings provide satisfactory long-term scar outcomes in enzymatically debrided deep dermal burns, with Kerecis® showing trends toward more physiological scar characteristics in selected parameters, warranting further patient-centered research.

Recent advances in burn care have highlighted the benefits of enzymatic debridement in reducing long-term scarring by preserving viable dermal structures. Nexobrid®, a bromelain-based enzymatic debridement agent, has become an established treatment modality for deep-dermal burns, particularly of the hand, due to its selective action and tissue-sparing properties. After debridement, the choice of dressing critically influences inflammation, re-epithelialization, and ultimately scar quality and skin function. In clinical practice, Suprathel®, a synthetic copolymer membrane, and Jelonet®, a paraffin-impregnated gauze, are widely used. While Suprathel® offers improved pain control and patient comfort, Jelonet® remains a cost-effective standard. Building on our previous intra-individual trial, which showed similar healing times but greater patient comfort with Suprathel®, this planned single-center, prospective long-term follow-up aims to address the lack of data on long-term scar quality and skin barrier function after enzymatic debridement. It includes the same 23 patients with deep-dermal hand burns who had received wound coverage with both Suprathel® and Jelonet® on comparable wound areas, assessed at 3, 6, and 12 months using objective instruments (Cutometer®, Mexameter®, Tewameter®, O2C®) and subjective scales (Vancouver Scar Scale, Patient and Observer Scar Assessment Scale). Both dressings resulted in favorable and largely comparable scar outcomes over 12 months, with no significant differences in elasticity, perfusion, or overall clinical scar appearance. Subtle yet statistically significant differences in transepidermal water loss (p < 0.01) and pigmentation (p < 0.01) indicated a trend toward enhanced epidermal barrier restoration and reduced hypopigmentation in Suprathel®-treated areas, although these effects did not translate into perceptible clinical advantages. These results confirm that both Suprathel® and Jelonet® are effective options for post-enzymatic debridement wound coverage, showing comparable long-term scar outcomes. The choice may reasonably depend on clinical workflow and dressing-management preferences, with Suprathel® remaining the standard in our burn center due to its reduced frequency of dressing changes.

Does enzymatic debridement reduce the occurrence of hypertrophic scarring in intermediate depth burns?

Friction injury occurs when a patient slides across a surface at high velocity, resulting in mechanical abrasion, laceration, and thermal burn. Mechanical abrasion removes tissue to a variable depth depending on surface texture in contact, and thermal burn devitalizes tissue to a variable depth based on contact pressure and transfer of kinetic energy. In these heterogenous wounds, tangential excision can excise healthy tissue alongside devitalized tissue, and other debridement techniques like hydrosurgery or dermabrasion may not reach deeper crevices created by abrasion and laceration. In addition, traditional skin grafts create significant donor site morbidity. This case series presents an early experience with a novel approach using bromelain-based enzymatic debridement combined with autologous skin cell suspension. Bromelain-based enzymatic debridement acts uniformly on a wound surface despite its topography, optimizing removal of devitalized tissue while preserving healthy tissue. Autologous skin cell suspension reduces donor site morbidity. This combined strategy minimizes dressing changes, optimizing pain control and enabling outpatient management. We observe rapid healing and outstanding cosmetic outcomes, and no patients experienced wound infection or other complications or required secondary procedures for nonhealing.

Enzymatic Debridement with NexoBrid® for Low-Temperature Burns

Primary cutaneous aspergillosis is a rare fungal infection in extremely preterm neonates. We report a male infant born at 25+5 weeks' gestation who developed necrotic lesions at the site of an umbilical catheter covered with an occlusive dressing. Culture confirmed Aspergillus fumigatus, and systemic liposomal amphotericin B combined with local enzymatic debridement and a non-adherent silicone wound contact layer was initiated after receipt of the culture result. The lesions resolved completely, leaving only a fine residual scar without functional impairment.This case emphasises the importance of early recognition, culture-based diagnosis and timely antifungal therapy in preterm neonates with catheter-related skin lesions, even when standard antifungal prophylaxis has been administered.

Bromelain-based enzymatic debridement (BBD) may selectively remove devitalised tissue in chronic wounds, but randomised evidence is limited. Following PRISMA and a PROSPERO-registered protocol (CRD420251116455), we searched MEDLINE, CENTRAL and Embase from inception to 8 Aug 2025 for randomised controlled trials in adults with chronic wounds comparing topical BBD versus standard care/vehicle. Two reviewers screened, extracted and assessed risk of bias. Primary outcomes were incidence of complete debridement (efficacy) and ≥ 1 adverse event (safety). Of 24 records, 3 RCTs (n = 314) met inclusion; 2 contributed complete-debridement data and 3 contributed adverse-event data. BBD increased complete debridement versus control (RR 2.81, 95% CI 1.15-6.86; I2 = 58.7). Safety was comparable (RR 1.02, 95% CI 0.76-1.36; I2 = 0), and leave-one-out analyses for adverse events showed no influential study. BBD improves the likelihood of complete debridement without increasing adverse events, suggesting a possible role in its use as a selective, non-surgical adjunct alongside guideline-directed care.

This post hoc analysis determined the correlation between wound bed preparation (WBP), defined as complete debridement of nonviable tissue and complete granulation tissue coverage, and wound closure, using data from a published, Consolidated Standards of Reporting Trials (CONSORT)-compliant randomized controlled trial that evaluated bromelain-based enzymatic debridement (BBD) compared with a placebo gel vehicle (GV) or nonsurgical standard of care (NSSOC) in patients with chronic venous leg ulcers (VLUs). Patients with chronic VLUs were randomized (3:3:2 ratio) to daily treatment with BBD, GV, or NSSOC for up to 2 weeks and followed up weekly with NSSOC for 12 weeks. Wound closure incidence was compared between those who did and did not achieve WBP by 14 days or anytime during the study. Data were analyzed from 119 VLUs. Among 80 wounds that achieved WBP anytime during the study, 42% healed; among 39 wounds without WBP, only 10.3% healed (relative risk [RR] = 4.1, p = 0.0004, negative predictive value [NPV] = 90%). Among 37 wounds that achieved WBP by 14 days, 54% healed; among 78 wounds that did not achieve WBP by 14 days, only 22% healed (NPV = 78%). Wounds were 2.4 times more likely to achieve closure anytime during the study, if they achieved WBP by 14 days (RR = 2.4, p = 0.0005). This landmark analysis confirms that WBP status is an early predictive variable of wound closure. WBP of chronic VLUs significantly increased the likelihood of wound closure and is a critical, though not sufficient, condition for healing.

Early surgical debridement and skin grafting of deep thermal burns are considered one of the cornerstones of modern burn care. Despite improvement in morbidity and long-term outcomes, the drawbacks of surgery include a non-selective debridement, need for an operating room, blood loss, and donor site scars. The first clinical trial with a pineapple-based concentrate of proteolytic enzymes for enzymatic debridement of deep burns was conducted at Soroka University Medical Center in the last 2 decades of the 20th century. As the treatment is selective, it is intended to reduce the need for surgical debridement and skin-grafting, as it spares viable tissue that may have the potential for spontaneous healing. Years later, after the completion of seven clinical trials, NexoBrid enzymatic debridement received its first approval for use by the European Medicines Agency in 2012. Since then, additional clinical trials including two multicenter RCT's were conducted around the world and the treatment is now approved for use in more than 40 countries worldwide. To date more than 14,000 patients have been treated with NexoBrid and more than 150 papers were published since the first clinical trial. We conducted a Pubmed and Google Scholar search for papers including the terms "NexoBrid" or "Bromelain enzymatic debridement" published between 18/12/2012 (European approval) and 1/3/2025, in which 146 relevant papers were found. This article summarizes the main lessons learned from these papers.

Traumatic tattoos, resulting from the accidental impregnation of foreign particles are common consequences of road traffic accidents and explosions. Unlike conventional tattoos, these occur when high-impact events embed foreign materials into the skin, causing persistent discoloration and cosmetic disfigurement. Preventing the permanent inclusion of these particles through immediate removal is widely considered as the best strategy. Nowadays, the preventing procedures by the means of scrubbing remain insufficient and the need for delayed additional methods is of the main causes of concern. Consequently, we aim to propose a new therapeutic protocol with enzymatic debridement to prevent and treat traumatic tattoos. In this prospective study, we included patients diagnosed with traumatic tattoos referred to our National Burn Center during 9 months (from June 2024 to March 2025). All were treated with enzymatic debridement (Nexobrid®) to remove necrotic tissues after initial cleaning of the wound. Pigmented surface was evaluated before and after enzymatic debridement. 15 consecutive patients were successfully treated with enzymatic debridement (Nexobrid®) under sedation within the 24 first hours after the initial incident. 92.5% of the surface of pigmented dermis was cleared from pigments after treatment, thus preventing the occurrence of traumatic tattoos. No adverse events were reported during the treatment. Enzymatic debridement presents a comprehensive approach to wound care in cases of traumatic tattoos, offering precision, tissue preservation, and user-friendly application, to optimize functional and cosmetic outcomes. These advantages position it as an effective alternative to more traditional methods, particularly in settings that require minimal invasiveness and maximal tissue conservation.

Enzymatic debridement with anacaulase-bcdb was approved by the US Food and Drug Administration in 2023. The purpose of this study is to compare outcomes from our first cohort of patients treated with this novel enzymatic agent. We compared patients treated with anacaulase-bcdb at our burn center from November 2023 to August 2024 to a 1:1 matched control group. Demographic, clinical, and photographic data were collected to ensure appropriate matching. Outcomes included: hospital length of stay, number of surgeries, time to first surgery, autograft size, total opioid and benzodiazepines received for wound care over the first 5days, pain/sedation scores during wound care, time to wound closure, and readmission data. Descriptive statistics were used to assess anacaulase-bcdb treatment practices, while non-parametric tests were used for all comparisons. 13 patients treated with anacaulase-bcdb were identified. Median (interquartile range) cohort age, total body surface area, and mechanism of injury were 46years (33.5, 59.5), 4.5% (2, 10.2), and flame (46.2%). No baseline differences were identified between groups. Anacaulase-bcdb was used before day 3 with regional anesthesia in all but 2 cases and successful eschar removal in 12 patients (92%). Patients treated with anacaulase-bcdb had a shorter time to first surgery from admission (4days [3, 5] vs 6 [5, 7], P = .017) and higher average maximum wound care pain scores during the first 5days (7 [6, 8] vs 5 [3, 7], P = .047). There was no difference in length of stay, area grafted, number of surgeries, total opioids/benzodiazepines received, or sedation scores.

Background: Enzymatic debridement with Nexobrid (NXB) is established for burn care, but specific outcomes in the elderly remain poorly characterized. This study evaluates the safety, efficacy, and clinical outcomes of NXB in patients aged ≥65 years. Methods: A retrospective case-series of 43 consecutive elderly patients (mean age 74.5 years) with deep partial- to full-thickness burns treated with NXB at a single burn center. Data on demographics, burn characteristics, treatment chronology, and complications were analyzed. Results: The median total burn surface area (TBSA) was 11%. NXB was applied selectively, with a mean debrided area of 7.41% TBSA, primarily on limbs and hands. While 76.7% of patients ultimately required surgical autografting, no patient required an escharotomy in NXB-treated areas. The mortality rate was 25.6%, which was lower than expected for a median revised Baux score of 90, which is expected to be more than 50%. Hypertrophic scarring occurred in 28.1% of survivors, associated with a prolonged median healing time of 63 days. Conclusions: In elderly burn patients, NXB facilitates precise eschar removal and reliably prevents compartment syndrome, demonstrating a strong safety profile even in high-risk individuals. Its primary benefit shifts from reducing surgical incidence to optimizing the wound bed for grafting. These findings support the use of NXB in the elderly, with the understanding that subsequent grafting is often still required due to age-related delayed healing.

Pathological evaluation of pseudoeschar formation after enzymatic debridement with nexobrid: a case report

Burn injuries over previously grafted tissue present a formidable challenge for excision and debridement, particularly when there are critical underlying structures such as bowel. Enzymatic debridement with the recently approved anacaulase-bcdb, a bromelain-based enzymatic debridement gel (Nexobrid®), presents an additional method of burn excision that may be useful in such a situation. This brief report presents the management of a complex third-degree burn over a remotely skin-grafted bowel mass using anacaulase-bcdb gel. This report is written with documented patient consent and approval by the Human Research Protection Program office in compliance with institutional policy. A 52-year-old man presented to our level I burn center with a third-degree 3% total body surface area contact burn to a remotely skin-grafted bowel mass. The patient was admitted with the decision to proceed with anacaulase-bcdb debridement of his wound to minimize the risk of compromising his underlying bowel. The patient underwent the debridement without any sign of succus emanating from the wound. Post-debridement, he was transitioned to a negative pressure wound dressing and discharged home. He continued receiving wound care at clinic follow-ups and eventually underwent complex open ventral hernia repair. This brief report provides a safe alternative to operative excision of wounds with underlying critical structures.