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Abstract

Millions of people worldwide suffer from chronic wounds, such as pressure sores, diabetic foot ulcers, and venous leg ulcers. Microbial biofilms, which are bacterial communities encased in extracellular matrices they produce on their own and that withstand host immune responses and antimicrobial treatments, are the main cause of these wounds' delayed healing and high recurrence rates. With a focus on cutting-edge natural treatment approaches, this review investigated biofilm formation mechanisms, resistance patterns, and persistence in chronic wounds. Bromelain, a proteolytic enzyme from pineapple (Ananas comosus), was highlighted in a thorough literature review that concentrated on recent developments in biofilm disruption. Pseudomonas aeruginosa and Staphylococcus aureus, two important biofilm-forming pathogens, have a high level of resistance to antibiotics and prolong chronic inflammation. Natural products hold significant promise in enhancing antimicrobial efficacy and disrupting biofilm structures. Bromelain enhances antibiotic penetration, promotes enzymatic debridement, and demonstrates broad-spectrum antibacterial and antibiofilm qualities. When used against mature biofilms, especially MRSA strains, the bromelain-N-acetylcysteine combination (BromAc) showed remarkable efficacy. While many natural substances exhibit antibiofilm properties, such as tea tree oil (which works against Candida albicans), tannic acid (which targets E. coli CsgD regulators), usnic acid (which inhibits P. aeruginosa adhesion), and ?-amylase (which disrupts extracellular matrices), bromelain stands out due to its special combination of matrix degradation and increased antibiotic permeability, according to comparative analysis. Synergistic combinations, such as flogomicina (NAC, bromelain, and plant extracts), increase the effectiveness of antibiotics and reduce bacterial growth by more than 80%. Although more comparative research is required to completely clarify its clinical potential in the management of chronic wounds, bromelain's triple therapeutic action proteolysis, antibiofilm activity, and wound healing promotion makes it a strong contender for both standalone and combination therapies.

Keywords

Biofilm, Chronic wounds, Bromelain, Antibiofilm, Wound healing, Natural agents, Enzymatic debridement

Introduction

Chronic wounds are a rising worldwide health problem, with an estimated 6.5 million United States patients alone and an annual cost of treatment of more than $25 billion. Such wounds failure to heal within 4-6 weeks with or without chronic wounds such as diabetic foot ulcers, pressure ulcers, and venous leg ulcers that all contribute to patient morbidity, healthcare cost, and prolonged hospital stay.(1) one of the most significant factors preventing chronic wound healing is the development of Microbial biofilms, which are aggregate colonies of bacteria in a self-produced matrix of extracellular polymeric substances (EPS).(2) these biofilm provide protective niches that cover microorganism from antimicrobial agents and host immune cells, significantly prevent infection control and hindering wound closure.(3) Although biofilms are  found in acute wounds, they are common in chronic wounds(4) ),  tend to be polymicrobial communities, such as  both Gram-positive and Gram-negative bacteria, such as  Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.(5)

Polysaccharides, proteins, lipids, and extracellular DNA (eDNA) EPS matrix contribute to structural stability and increased bacterial adhesion and in addition creates diffusion barrier that prevents penetration by antibiotics and clearance by immune cells.(6) ) The architectural sophistication makes standard treatments such as topical antibiotics and mechanical debridement inadequate for total eradication of biofilm.(7)

Current studies have reviled promising antibiofilm candidates acting against multiple disruption mechanisms: quorum sensing inhibition, matrix-degrading enzymes, and biofilm disassembly agent(8) Natural bioactive compounds such as usnic acid, tannic acid, bromelain, and tea tree oil have shown great potential to biofilm structure modification and augmentation of conventional treatment efficacy(9) (10) Of these drugs, bromelain, a mixture of proteolytic enzymes isolated from the pineapple (Ananas comosus), has gained prominence due to its potent antimicrobial, anti-inflammatory, and enzymatic debridement activities. Beyond inhibiting the structure of biofilms through proteolytic activity, bromelain enhances the absorption of antibiotics and facilitates tissue regeneration, making it a highly potential agent for the treatment of chronic wounds.(11)  The pathophysiology of wound-related biofilms, their resistance mechanisms, and new antibiofilm therapies are discussed below, with specific regard to the therapeutic potential of bromelain in the treatment of chronic wounds.

MICROBIAL BIOFILM

Bacterial biofilms are complex, structured microbial communities where microbial cells are encased in a matrix of extracellular polymeric substance.(2) (3) “Biofilm is the unique pattern of growth in the life cycle of microbes that provides specific properties, advantages and higher level of organization to the free living bacterial cells during colonization”(12) Different bacterial species can develop distinct biofilm architectures even under the same environmental conditions, which is both species specific and dependent on environmental condition.(13)

The following steps make up the biofilm growth process: (1) microorganisms binding to a surface or to one another; (2) microcolony creation; (3) biofilm maturation; and (4) biofilm dispersal (13). The organic polymers of microbial origin known as extracellular polymeric substances (EPS) are engaged in the interactions between bacterial cells and their surroundings.  “a strong and sticky framework”. EPS is a non-cellular three-dimensional structure made up of proteins, glycoproteins, proteoglycans, and exopolysaccharides.(14)

Figure 1: Biofilm growth process- 1. Microorganism binding- attachment of free-floating bacteria to the surface. 2.  Microcolony formation- proliferation of attached cells and begin forming clusters. 3. Biofilm maturation- development of a complex 3D structure with an extracellular polymeric matrix. 4. Biofilm dispersal- some cells detach and revert back to a planktonic state, enabling colonization of new cities.

Wound biofilm

Chronic wounds are those with a tendency to last longer than four to six weeks and do not heal through the normal phases of healing in the normal time frame. They tend to be linked to diseases including diabetes, ischemia, infection, or the creation of microbial biofilms.(4) (15) It is challenging to treat them with standard therapy since they have a tendency to stay in a chronic inflammatory process.

To confirm this statement, microscopic analysis of chronic wound samples has identified tightly aggregated colonies of bacteria covered by an extracellular matrix, a feature of biofilms. These morphological features are strong evidence for the presence of biofilms in chronic wounds. Acute wound samples, however, rarely show such structures, which confirms that biofilms are comparatively infrequent in acute wound pathology.(4)

Figure 2: wound biofilm- a mature biofilm with in wound bed.

The resistance and persistence of biofilms also depend on their maturity; Biofilm resistance to disinfectants enhanced by age of biofilm. (16) In an in-vivo model, Pseudomonas aeruginosa biofilm infections were found to cause a significant delay in wound healing by an average of 2 to 4 weeks compared to uninfected controls, indicating the central role of biofilms in the pathophysiology of chronic wounds and the need for effective anti-biofilm therapies.(17) Among the most serious pathogens, Staphylococcus aureus is a main cause of biofilm formation (18) One of its principal surface proteins, designated as Bap (biofilm-associated protein), has 2,276 amino acids and is involved in adhesion and biofilm formation in a wide range of bacterial species. Bap has also been found to enable specific higher intramammary adherence and continuous biofilm formation, as well as the persistence of S. aureus infections.(19) Staphylococcus aureus isolates with a virulent potential to form biofilms are isolated from chronic wounds. (20)  Methicillin-resistant S. aureus (MRSA) isolates were highly resistant to clindamycin, erythromycin, and penicillin G, whereas methicillin-sensitive S. aureus (MSSA) isolates commonly showed resistance to penicillin G, cotrimoxazole, and ciprofloxacin. Furthermore, Gram-negative bacteria from chronic wounds have been highly resistant to a number of antibiotics, including amoxicillin-clavulanic acid, ceftazidime, ciprofloxacin, cefoxitin, cephalothin, and cefuroxime. These findings emphasize the clinical challenge posed by drug-resistant biofilm-associated bacteria in the treatment of chronic wounds.

Compared to their non-biofilm-producing cousins, biofilm-producing bacteria are significantly more resistant to antibiotics and disinfectants and therefore harder to treat (21) ) This is confirmed by a study compared mupirocin cream and triple antibiotic ointment for the treatment of Staphylococcus aureus infections. Both were effective against planktonic (free- floating) bacteria but significantly less effective against mature biofilms, despite identical initial bacterial numbers. These findings refer to the reduced susceptibility of biofilm- associated infections and highlight the therapeutic challenge posed by biofilm-producing pathogens. (22) Additionally, polymicrobial biofilms recovered slowly compared to mono-species infection due to increased microbial synergy and increased antimicrobial tolerance. (5) Scanning electron microscopy illustrates that even the most efficient wound care regimen cannot completely eradicate biofilm in a single session, proving biofilm resistance and the need for extensive and sustained treatment. (7)

This issue is not exclusive to only wound infections, Biofilm formation is the single most important cause of device-associated infections, particularly central venous catheter (CVC) associated infections. These catheter-related infections, primarily caused by biofilm-forming bacteria. About 90% of staphylococcal species, including S. epidermidis, S. aureus, and others, produce biofilms. Apart from gram-negative bacteria like E.coli, K. pneumoniae, P. aeruginosa, Candida albicans has a 100% rate of biofilm prevalence, indicating the central role of biofilms in catheter infections.(23)  One of the most helpful first-line therapies for the management of biofilm burden in chronic wounds is debridement. The procedure entails the removal of infected or dead tissue and foreign bodies from the wound bed to a level when healthy tissue surrounding the wound becomes visible,(24) is applicable to any lesion, wherever it is from or whatever it is diagnosed as. There are a number of types of debridement Autolytic Debridement, Biological Debridement, Enzymatic Debridement, Surgical Debridement with Sharp Instruments, Mechanical Debridement.

TABLE 1: KEY CHARACTERISTICS OF TRADITIONAL DEBRIDEMENT METHODS IN WOUND CARE

Feature

Debridement

Invasiveness

Invasive (surgical, mechanical, or enzymatic).

Pain & Discomfort

Can be painful; may require anesthesia.

Target Specificity

Non-specific removal of both biofilm and necrotic tissue.

Application Frequency

Repeated procedures can cause damage to healing tissue.

Use in High-Risk Patients

May not be suitable for immunocompromised or fragile patients.

Prevention Capability

Cannot prevent biofilm formation; reactive approach

Tissue Preservation

Risk of damaging granulation tissue

Ease of Use

Requires trained personnel or clinical setup

Although the mechanical method remains a critical strategy, molecular approaches have also evidenced potential in interfering with biofilm formation.

ANTIBIOFILM

The term "antibiofilm" is used to describe any substance or material that blocks or disrupts the formation and growth of microbial biofilms. A wide range of antibiofilm agents has been identified. Numerous compounds, including certain natural extracts, synthetic compounds, enzymes, peptides, chelating agents, polyphenols, and other antibiotics, have been reported to possess anti-biofilm action. Anti-biofilm agents appear to act through different mechanisms against different bacterial species to block biofilm formation.

MECHANISMS OF BIOFILM DISRUPTION

Biofilms in chronic wounds have a high degree of resistance to antimicrobial agents, owing to their well-developed structure and adaptive processes. Interference with these processes using natural antibiofilm agents has been proposed as a potential approach. A number of different modes of action have been described.

QOURAM SENSING INHIBITORS (QSI)

Quorum sensing is a communicative process employed by bacteria to quantify their cell density through chemical signals. When the concentration of the signal surpasses a certain threshold, it triggers group activities such as biofilm formation, making infections difficult to treat.(25)

N-acyl homoserine lactone synthetic analogs have the potential to interfere with quorum sensing by inhibiting LuxR activation, thereby disrupting bacterial communication and inhibiting biofilm formation (26) (27) In addition, naturally occurring compounds isolated from plants have shown inhibitory activities against quorum sensing. In particular, furocoumarins found in grapefruit juice are recognized as compounds that block both the AI-1 and AI-2 signal pathways, leading to significant biofilm inhibition in Salmonella typhimurium, Pseudomonas aeruginosa, and Escherichia coli O157:H7. These observations imply that compounds isolated from plants, such as furocoumarins, have the potential to act as natural antibiofilm compounds by interfering with the quorum sensing processes of microorganisms.(28)

MATRIX DEGRADING ENZYM

Biofilm matrix, which is dominated by polysaccharides, proteins, and extracellular DNA (eDNA), confers structural reinforcement and antimicrobial resistance. Enzymes like Dispersin B and DNase I can break down biofilm structures, inhibit adhesion, and increase the effectiveness of antimicrobial agents like povidone-iodine.(6)

In addition, α-amylase, a polysaccharide-breaking enzyme, has been found to interfere with Staphylococcus aureus biofilms. α-amylase commercial products will prevent cell aggregation, remove preformed biofilms, and inhibit biofilm formation.(29)

INHIBITION OF BACTERIAL CELL DIVISION

Certain antimicrobial peptides, such as proline-rich peptides such as pyrrhocoricin, disrupt intracellular protein folding by inhibiting the chaperone protein DnaK from carrying out its function. DnaK aids in bacterial stress response and protein repair. Pyrrhocoricin, by inhibiting DnaK from acting, inhibits vital bacterial activities and reduces biofilm formation and maintenance.(30)

CLEAVAGE OF PEPTIDOGLYCAN

Disruption of peptidoglycan, a structural molecule of the cell wall, may disrupt the biofilm and decrease bacterial adhesion. Natural products such as tannic acid may induce IsaA, S. aureus lytic transglycosylase, that hydrolyses the β-1,4 glycosidic bond between MurNAc and GlcNAc, disrupting the cell wall.(31) (32) Hydrolysis may also liberate biofilm-controlling signalling molecules and affect anchoring surface proteins.

PREVENTION VIA BIOFILM DISASSEMBLY

During biofilm disassembly, embedded cells are released and the extracellular matrix is actively broken down. Proteases, DNases, and surfactants can all initiate this process, which is frequently controlled by quorum-sensing systems like Staphylococcus aureus's agr system.(33) Another way to cause biofilm breakdown is to target amyloid-like fibres, including curli in E. coli and TasA in Bacillus subtilis. Parthenolide and FN075 are examples of inhibitors that disrupt these structural proteins. Likewise, D-amino acids, such as D-tyrosine, can cause disintegration at low levels, although in vivo toxicity is still an issue.(34) Usnic acid is one example of a natural substance that has antibiofilm activity by decreasing EPS synthesis and disrupting quorum sensing pathways, which results in changed biofilm shape and decreased biofilm bulk.(35) (36) In brief antibiofilm agents and their mechanisms is provided in Table 1.

Combining antibiofilm agents with conventional antibiotics significantly enhances therapeutic outcomes by disrupting the biofilm barrier and increasing drug penetration. These strategies represent a promising direction in the management of chronic and device-associated infections. 

Figure 3: Schematic representation of key mechanisms by which agents disrupt biofilms. These include inhibition of quorum sensing, degradation of the extracellular matrix, disruption of cell division, cleavage of peptidoglycan, biofilm disassembly, and proteolytic activity.

TABLE 2: OVERVIEW OF ANTIBIOFILM AGENTS AND THEIR MECHANISMS OF ACTION

Category

Agent /Example

Mechanism of Action

Target Organisms

Notes

Quorum Sensing Inhibitors

Synthetic AHL analogs

Block LuxR activation to disrupt quorum sensing

P. aeruginosa, E. coli

Inhibits biofilm gene regulation

 

Furocoumarins (grapefruit juice)

Inhibit AI-1 and AI-2 signaling pathways

S. typhimurium, P. aeruginosa, E. coli

Plant-derived, natural quorum sensing blocker

Matrix-Degrading Enzymes

Dispersin B, DNase I

Degrade eDNA and PNAG to disrupt matrix and enhance antimicrobial action

S. aureus, S. epidermidis

Used in conjunction with iodine or antibiotics

 

α-Amylase

Breaks down extracellular polysaccharides

S. aureus

Reduces preformed biofilms and inhibits aggregation

Cell Division Inhibitors

Pyrrhocoricin

Inhibits DnaK chaperone protein, interfering with protein folding and stress response.

Broad spectrum (G+)

Reduces bacterial viability and biofilm sustainability

Peptidoglycan Cleaving Agents

Tannic Acid

Upregulates IsaA, a lytic transglycosylase, weakening cell wall

S. aureus

Does not harm planktonic viability

Biofilm Disassembly Agents

Proteases, DNases, surfactants

Degrade matrix and promote detachment

S. aureus, B. subtilis, E. coli

Often regulated by agr and other QS systems

 

Parthenolide, FN075

Inhibit amyloid fiber (TasA/curli) formation

B. subtilis, E. coli

Target protein–protein interactions in matrix assembly

 

D-Tyrosine, D-Cysteine

Alter EPS production; disrupt biofilm architecture

P. aeruginosa, A. baumannii, B. subtilis

Effective in vitro; toxic in vivo at high concentrations

 

Usnic Acid

Inhibits EPS production, quorum sensing, and hyphal transition

S. aureus, Candida albicans, P. aeruginosa

Lichen-derived; broad-spectrum antibiofilm activity

BROMELAIN

Bromelain is a cysteine protease enzyme complex first identified in Brazilian pineapple by Peckold et al. (37) is primarily extracted from the stem and fruit of the pineapple plant (Ananas comosus Merr.), with the stem being the major commercial source other parts such as the pineapple core and pulp also offer cost-effective alternatives for bromelain production.(38)  The enzymatic activity of fruit bromelain and stem bromelain varies depending on the extraction source, with stem bromelain showing greater enzymatic potency at least eight different isoforms of bromelain have been identified from the stem; each is made up of a heavy chain with five disulfide bonds and a light chain. A sulfhydryl proteolytic enzyme that is unique to cysteine proteinases ) is the main active ingredient (39) (40)

Crude bromelain is a complex enzymatic mixture, that including cysteine proteases like fruit bromelain, stem bromelain, ananain, and comosain as well as other enzymes such as phosphatases, peroxidases, ribonucleases, cellulases, protease inhibitors, glycoproteins, carbohydrates, and organically bound calcium.(41) This diverse biochemical composition gives bromelain's potent antimicrobial, anti-inflammatory, and wound-healing properties, makes it as a promising agent in biomedical and wound care applications.

Bromelain exhibits optimal activity around pH 6–7 and has an isoelectric point (pI) of 9.55(42)  glass transition temperature is about 61 °C, as determined by Differential Scanning Calorimetry (DSC), indicates that drying should be conducted below this threshold to preserve activity. (43) While its simple extracts show peak activity at pH 7 and 50 °C, ethanol- precipitated forms optimal performance at pH 8 and 60 °C. (44) Bromelain has shown promise as an oxidizing agent in addition to its proteolytic activity.(45) Crucially, bromelain has been used extensively as a bioenhancer for antibiotics because of its low systemic cytotoxicity, which has greatly improved antimicrobial outcomes in diseases like sinusitis, pneumonia, bronchitis, and skin infections brought on by Staphylococcus aureus. (46) (47) According to a pharmaco-kinetic studies by bromelain taken orally can be absorbed in trace amounts in a physiologically active, with detectable plasma concentrations that last for up to 48 hours. This reflects its potential for systemic treatment when taken orally for wound or infection treatments.(48)

ANTIBIOFILM AND ANTIBACTERIAL ACTIVITY

Bromelain is a natural choice for the treatment of periodontal infections because it has demonstrated antibacterial action against important dental and skin pathogens such S. mutans and P. gingivalis.(49) (50) bromelain not only showed intrinsic antibacterial action against Staphylococcus aureus and Staphylococcus epidermidis, but it also improved the effectiveness of 14 other antibiotics, particularly those that target Gram-negative bacteria. Interestingly, amoxicillin, erythromycin, ciprofloxacin, and gentamycin all showed synergistic benefits. (51)

As antibiofilm agent bromelain, particularly in combination with N-acetylcysteine (BromAc), has shown remarkable potential. In vitro studied have demonstrated that BromAc dissolve more than 80% biofilm dissolution in Pseudomonas aeruginosa, underscoring its potential utility in managing chronic and device-associated infections. (11) furthermore 1% bromelain significantly inhibited biofilm formation (up to 4-fold) and effectively disrupted mature biofilms (up to 6.4-fold), with the strongest effects observed in methicillin-resistant S. aureus strains. These effects are attributed primarily to its proteolytic activity, with some support from DNase-like action.(52)

WOUND HEALING AND ENZYMATIC DEBRIDEMENT

Bromelain aids in the efficient removal of tissue in chronic wound models and has been used successfully in enzymatic wound debridement. Clinical trials highlight its usefulness as a safe, non-surgical alternative for wound treatment by reporting an average debridement of 68% with no significant side effects observed. (53) Bromelain-loaded nanoparticles (NPs) improved re- epithelialization in animal wound models by enhancing sustained enzymatic release when added to chitosan-based hydrogels.(54)

TABLE 3: KEY STUDIES ON BROMELAIN’S ANTIBACTERIAL, ANTIBIOFILM, AND WOUND-HEALING ACTIONS

Study

Target Organism

Key Findings

Mechanism

Notes

Praveen et al., 2014

Streptococcus mutans, Enterococcus faecalis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis

Bromelain showed antibacterial activity with MICs ranging from 2–31.25 mg/mL

Proteolytic action; antibacterial

Most effective against S. mutans (2 mg/mL) and P. gingivalis (4.15 mg/mL); indicates potential as adjunct in periodontal therapy

Carter et al., 2021(11)

Pseudomonas aeruginosa (3 strains)

Bromelain + NAC (BromAc) dissolved >80% biofilm on mesh in vitro

Synergistic mucolytic activity

Strain-dependent; NAC alone promoted growth in 2 strains

Bayat et al., 2022(55)

Wound models (animal)

Bromelain NPs in chitosan hydrogel enhanced debridement and re-epithelialization

Sustained enzymatic release

92% encapsulation; stable at 4 and 25 °C

Shoham et al., 2021(56)

Chronic wounds (clinical, various etiologies)

68% average debridement; effective in venous/diabetic wounds

Topical enzymatic proteolysis

Safe, non-surgical alternative; mild pain only adverse event

Silva et al., 2023 (57)

Staphylococcus aureus (incl. MRSA)

1% bromelain inhibited biofilm formation (4×) and disrupted biofilms (6.4×)

Proteolytic activity; some DNase effect

No MIC effect; strong action on MRSA from chronic wounds

Omotoyinbo et al., 2025

Staphylococcus aureus, Staphylococcus epidermidis, various Gram-negative bacteria

Bromelain enhanced antibiotic efficacy and showed inherent antibacterial activity; optimum activity at 40°C, pH 7.0

Synergistic antibacterial action; improved antibiotic absorption

Crude and purified bromelain tested; best synergy observed with β-lactam and macrolide antibiotics

COMPARATIVE EVALUATION OF BROMELAIN AND OTHER NATURAL ANTIBIOFILM AGENTS

Numerous natural substances with different modes of action have demonstrated anti-biofilm qualities. Because of its combined potential to increase antibiotic permeability and break down the components of the biofilm matrix, bromelain stands out from the others. More research is being done on the possibility of bromelain as a therapy, both on its own and in conjunction with other natural anti-biofilm medications.

The antibiofilm and antibacterial activity of flogomicina, a natural antioxidant mixture of NAC, bromelain, and other plant extracts, was significantly stronger than that of NAC alone. It reduced E. Coli and P. mirabilis growth by over 80% and improved amoxicillin efficacy over 14 days, indicating a synergistic effect and the potential for reducing antibiotic dosage.(58) Manuka honey, tea tree oil, and phytochemicals such as usinc acid, tannic acid, and eugenol also exhibit significant antibiofilm activity. (59) (60)

Tea tree oil (TTO) and its active ingredient terpinen-4-ol have been shown to have effective antibiofilm activity against Candida albicans, even resistant strains. A 60-second exposure to either TTO (17.92 mg/mL) or terpinen-4-ol (8.86 mg/mL) significantly inhibited biofilm growth, suggesting their potential use as natural antifungal agents in the treatment of oral candidiasis.(61) Tannic acid inhibits biofilm formation of E coli by targeting the curli subunit gene D (CsgD) regulators, which controls matrix development and curli production, additionally it also modulate biofilm regulated gene expression and enhance signalling of indole, highlighting its potential as antibiofilm agent.(62)

A lichen derived compound usnic caid, shown strong antibiofilm activity by preventing adhesion, EPS production and virulence factors in Pseudomonas aeruginosa, Staphylococcus aureus. It makes promising natural antibiofilm candidate by biofilm structure and reduce biomass.(59) α-Amylase is a glycoside hydrolase, it effectively disrupts Pseudomonas aeruginosa, Staphylococcus aureus biofilms in both monoculture and mixed species model. These enzymes degraded the extracellular matrix, reduced biofilm biomass, and enhanced the efficacy of antibiotics in vitro and in vivo. According to the study, glycoside hydrolase treatment is a safe and effective way to treat chronic wound infections linked to biofilms.(63)

Consequently, bromelain can be used as standalone antibiofilm agent and also as combination therapies for synergetic effect. Further comparative analysis is needed to find mechanistic diversity, relative efficacy and clinical potential of bromelain versus natural other antibiofilm agents in both mono and polymicrobial wound infections.

TABLE 4: COMPARATIVE SUMMARY OF NATURAL AND ENZYMATIC ANTIBIOFILM AGENTS

Agent

Source/ Type

Mechanism of Action

Target Organisms

Bromelain

Enzyme obtained from pineapple stem

Biofilm matrix proteolysis, enhance antibiotic penetration.

S. aureus, P. aeruginosa, E. coli, MSRA

Tannic Acid

Polyphenol (plants)

Represses CsgD regulator, synthesis of curli, and biofilm- related genes.

S. aureus, Agrobacterium tumefaciens, E. coli,

Usnic Acid

Lichen derived compound

interferes with virulence genes, adhesion, and EPS structure.

S. aureus, P. aeruginosa, Candida albicans

Tea Tree Oil

Essential oil (Melaleuca)

breaks down membranes; terpinen-4-ol prevents metabolism and adhesion.

C. albicans, S. aureus, E. coli

α-Amylase

Enzyme (microbial/plant)

EPS's extracellular polysaccharides are hydrolysed.

S. aureus, P. aeruginosa, MRSA, V. cholerae

CONCLUSION

The presence of robust microbial biofilms that delay healing and contribute to antibiotic resistance makes chronic wounds persistent therapeutic issue. These bacterial communities, which are dominated by pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, use complex defence strategies include altered cell physiology, extracellular matrix formation, and quorum sensing. Innovative approaches to therapy must be explored because conventional treatments often prove insufficient against these well-established biofilms. Natural agents show promising antibiofilm agents due to different mechanism of action, synergistic activity with conventional therapies and biocompatibility. This review reflects several affective strategies; quorum sensing inhibition, enzymatic matrix degradation, disruption of cell division, and biofilm disassembly. Among these approaches bromelain exhibits exceptional versatility through proteolytic activity, synergistic effect with antibiotics, biofilm disruption capability, wound healing enhancement. The clinical evidence that support bromelain's efficacy includes significant biofilm inhibition (up to 4-fold reduction in formation, 6.4-fold reduction in mature biofilms), enhanced antibiotic synergy.

FUTURE PROSPECTS

Future research should focus on optimized delivery system with standardized formulations, and well-designed clinical trial for comparing bromelain-based therapies with existing treatment for diverse wound type. Furthermore, combination therapy demonstrating bromelain synergistic effect with conventional antibiotics and with other natural agents to maximize therapeutic outcome while minimizing adverse effects.  Integrating cost effective analysis, patient reported outcome, long term follow-up in to future trials will provide correct understanding of bromelain effect in wound treatment. This direction will help for robust evidence-based procedure for broader clinical application.

ACKNOWLEDGMENT

The author expresses sincere gratitude to all researchers whose work has been cited in this review. Appreciation is also extended to those who provided insightful feedback and moral support during the preparation of this article. Their contributions were invaluable to the completion of this work.

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  23. Mishra R, Panda AK, De Mandal S, Shakeel M, Bisht SS, Khan J. Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens. Front Microbiol. 2020;11:566325.
  24. Ramundo J, Gray M. Enzymatic Wound Debridement. J Wound Ostomy Continence Nurs. 2008 Jun;35(3):273.
  25. Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–46.
  26. Schaefer AL, Hanzelka BL, Eberhard A, Greenberg EP. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol. 1996 May;178(10):2897–901.
  27. Reverchon S, Chantegrel B, Deshayes C, Doutheau A, Cotte-Pattat N. New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing. Bioorg Med Chem Lett. 2002 Apr 22;12(8):1153–7.
  28. Girennavar B, Cepeda ML, Soni KA, Vikram A, Jesudhasan P, Jayaprakasha GK, et al. Grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria. Int J Food Microbiol. 2008 Jul 15;125(2):204–8.
  29. Craigen B, Dashiff A, Kadouri DE. The Use of Commercially Available Alpha-Amylase Compounds to Inhibit and Remove Staphylococcus aureus Biofilms. Open Microbiol J. 2011;5:21–31.
  30. Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L. The Antibacterial Peptide Pyrrhocoricin Inhibits the ATPase Actions of DnaK and Prevents Chaperone-Assisted Protein Folding. Biochemistry. 2001 Mar 1;40(10):3016–26.
  31. Stapleton MR, Horsburgh MJ, Hayhurst EJ, Wright L, Jonsson IM, Tarkowski A, et al. Characterization of IsaA and SceD, Two Putative Lytic Transglycosylases of Staphylococcus aureus. J Bacteriol. 2007 Oct 15;189(20):7316–25.
  32. Payne DE, Martin NR, Parzych KR, Rickard AH, Underwood A, Boles BR. Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner. Infect Immun. 2013 Feb;81(2):496–504.
  33. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP. Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol. 2004 Mar;186(6):1838–50.
  34. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R. D-amino acids trigger biofilm disassembly. Science. 2010 Apr 30;328(5978):627–9.
  35. Romero D, Aguilar C, Losick R, Kolter R. Amyloid fibers provide structural integrity to Bacillus subtilis biofilms. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2230–4.
  36. Schaub RE, Dillard JP. The Pathogenic Neisseria Use a Streamlined Set of Peptidoglycan Degradation Proteins for Peptidoglycan Remodeling, Recycling, and Toxic Fragment Release. Front Microbiol. 2019;10:73.
  37. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988 Feb 1;22(2):191–203.
  38. Fissore A, Marengo M, Santoro V, Grillo G, Oliaro-Bosso S, Cravotto G, et al. Extraction and Characterization of Bromelain from Pineapple Core: A Strategy for Pineapple Waste Valorization. Processes. 2023 Jul;11(7):2064.
  39. Gautam SS, K. S, Dash V, Goyal AK, Rath G. Comparative study of extraction, purification and estimation of bromelain from stem and fruit of pineapple plant. Thai J Pharm Sci. 2010 Jan 1;34(2):67–76.
  40. Hatano K ichi, Takahashi K, Tanokura M. Bromein, a Bromelain Inhibitor from Pineapple Stem: Structural and Functional Characteristics. Protein Pept Lett. 25(9):838–52.
  41. Rowan A, Buttle D, Barrett A. The cysteine proteinases of the pineapple plant. Biochem J. 1990 Apr 1;266:869–75.
  42. Novaes LCL, Jozala AF, Mazzola P, Pessoa A. The influence of pH, polyethylene glycol and polyacrylic acid on the stability of stem bromelain. Braz J Pharm Sci. 2014;50(2):371–80. doi:10.1590/S1984-82502014000200017.
  43. Devakate RV, Patil VV, Waje SS, Thorat BN. Purification and drying of bromelain. Sep Purif Technol. 2009 Jan 12;64(3):259–64.
  44. Bianca Martins, Robson Rescolino, Diego De Freitas Coelho, Foued Espindola, Beatriz Zanchetta, Elias Basile Tambourgi, et al. Characterization of bromelain from ananas comosus agroindustrial residues purified by ethanol factional precipitation. Chem Eng Trans. 2014;37:781–6.
  45. Vejai Vekaash CJ, Kumar Reddy TV, Venkatesh KV. Effect of vital bleaching with solutions containing different concentrations of hydrogen peroxide and pineapple extract as an additive on human enamel using reflectance spectrophotometer: An: in vitro: study. J Conserv Dent Endod. 2017 Oct;20(5):337.
  46. AlSheikh HMA, Sultan I, Kumar V, Rather IA, Al-Sheikh H, Tasleem Jan A, et al. Plant-Based Phytochemicals as Possible Alternative to Antibiotics in Combating Bacterial Drug Resistance. Antibiotics. 2020 Aug 4;9(8):480.
  47. Ryan RE. A double-blind clinical evaluation of bromelains in the treatment of acute sinusitis. Headache. 1967;7(1):13–7.
  48. Castell JV, Friedrich G, Kuhn CS, Poppe GE. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol-Gastrointest Liver Physiol. 1997 Jul;273(1):G139–46.
  49. Chandwani ND, Maurya N, Nikhade P, Chandwani J. Comparative evaluation of antimicrobial efficacy of calcium hydroxide, triple antibiotic paste and bromelain against Enterococcus faecalis: An: In Vitro: study. J Conserv Dent Endod. 2022 Feb;25(1):63.
  50. 50.            Varilla C, Marcone M, Paiva L, Baptista J. Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary. Foods. 2021 Sep 23;10(10):2249.
  51. O.v O, F.l O, B.i O, D.m S, M DV. Exploring the Therapeutic Potential of Bromelain from Pineapple Fruit Peel: Enzymatic Activity and Antibiotic Synergy. Int J Biochem Res Rev. 2025 May 6;34(3):118–27.
  52. Silva MP, Calomino MA, Teixeira LA, Barros RR, de Paula GR, Teixeira FL. Antibiofilm activity of bromelain from pineapple against Staphylococcus aureus. Acta Sci Biol Sci. 2023;45:e65725.
  53. Shoham Y, Krieger Y, Tamir E, Silberstein E, Bogdanov?Berezovsky A, Haik J, et al. Bromelain?based enzymatic debridement of chronic wounds: A preliminary report. Int Wound J. 2018 Apr 25;15(5):769–75.
  54. Bayat S, Zabihi AR, Farzad SA, Movaffagh J, Hashemi E, Arabzadeh S, Hashemi M. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021;24(10):1404–12.
  55. Bayat S, Rabbani Zabihi A, Amel Farzad S, Movaffagh J, Hashemi E, Arabzadeh S, et al. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021 Oct;24(10):1404–12.
  56. Shoham Y, Krieger Y, Tamir E, Silberstein E, Bogdanov-Berezovsky A, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: A preliminary report. Int Wound J. 2018;15(5):769–75. doi:10.1111/iwj.12925. PMID: 29696785; PMCID: PMC7950085.
  57. Carter CJ, Pillai K, Badar S, Mekkawy AH, Akhter J, Jefferies T, Valle SJ, Morris DL. Dissolutionof biofilm secreted by three different strains of Pseudomonas aeruginosa with bromelain, N-acetylcysteine, and their combinations. Appl Sci. 2021;11(23):11388.
  58. Amante C, De Soricellis C, Luccheo G, Luccheo L, Russo P, Aquino RP, et al. Flogomicina: A Natural Antioxidant Mixture as an Alternative Strategy to Reduce Biofilm Formation. Life. 2023 Apr;13(4):1005.
  59. Pompilio A, Riviello A, Crocetta V, Di Giuseppe F, Pomponio S, Sulpizio M, et al. Evaluation of antibacterial and antibiofilm mechanisms by usnic acid against methicillin-resistant Staphylococcus aureus. Future Microbiol. 2016 Oct;11:1315–38.
  60. Morroni G, Alvarez-Suarez JM, Brenciani A, Simoni S, Fioriti S, Pugnaloni A, et al. Comparison of the Antimicrobial Activities of Four Honeys From Three Countries (New Zealand, Cuba, and Kenya). Front Microbiol. 2018;9:1378.
  61. Francisconi RS, Huacho PMM, Tonon CC, Bordini EAF, Correia MF, Sardi J de CO, et al. Antibiofilm efficacy of tea tree oil and of its main component terpinen-4-ol against Candida albicans. Braz Oral Res. 2020 Jun 5;34:e050.
  62. Long J, Yang C, Liu J, Ma C, Jiao M, Hu H, et al. Tannic acid inhibits Escherichia coli biofilm formation and underlying molecular mechanisms: Biofilm regulator CsgD. Biomed Pharmacother. 2024 Jun 1;175:116716.
  63. Fleming D, Chahin L, Rumbaugh K. Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds. Antimicrob Agents Chemother. 2017 Feb;61(2):e01998-16.

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  21. Banu A, Noorul Hassan MM, Rajkumar J, Srinivasa S. Spectrum of bacteria associated with diabetic foot ulcer and biofilm formation: A prospective study. Australas Med J. 2015;8(9):280–5.
  22. Davis SC, Ricotti C, Cazzaniga A, Welsh E, Eaglstein WH, Mertz PM. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc. 2008;16(1):23–9.
  23. Mishra R, Panda AK, De Mandal S, Shakeel M, Bisht SS, Khan J. Natural Anti-biofilm Agents: Strategies to Control Biofilm-Forming Pathogens. Front Microbiol. 2020;11:566325.
  24. Ramundo J, Gray M. Enzymatic Wound Debridement. J Wound Ostomy Continence Nurs. 2008 Jun;35(3):273.
  25. Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–46.
  26. Schaefer AL, Hanzelka BL, Eberhard A, Greenberg EP. Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol. 1996 May;178(10):2897–901.
  27. Reverchon S, Chantegrel B, Deshayes C, Doutheau A, Cotte-Pattat N. New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing. Bioorg Med Chem Lett. 2002 Apr 22;12(8):1153–7.
  28. Girennavar B, Cepeda ML, Soni KA, Vikram A, Jesudhasan P, Jayaprakasha GK, et al. Grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria. Int J Food Microbiol. 2008 Jul 15;125(2):204–8.
  29. Craigen B, Dashiff A, Kadouri DE. The Use of Commercially Available Alpha-Amylase Compounds to Inhibit and Remove Staphylococcus aureus Biofilms. Open Microbiol J. 2011;5:21–31.
  30. Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L. The Antibacterial Peptide Pyrrhocoricin Inhibits the ATPase Actions of DnaK and Prevents Chaperone-Assisted Protein Folding. Biochemistry. 2001 Mar 1;40(10):3016–26.
  31. Stapleton MR, Horsburgh MJ, Hayhurst EJ, Wright L, Jonsson IM, Tarkowski A, et al. Characterization of IsaA and SceD, Two Putative Lytic Transglycosylases of Staphylococcus aureus. J Bacteriol. 2007 Oct 15;189(20):7316–25.
  32. Payne DE, Martin NR, Parzych KR, Rickard AH, Underwood A, Boles BR. Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner. Infect Immun. 2013 Feb;81(2):496–504.
  33. Yarwood JM, Bartels DJ, Volper EM, Greenberg EP. Quorum sensing in Staphylococcus aureus biofilms. J Bacteriol. 2004 Mar;186(6):1838–50.
  34. Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R. D-amino acids trigger biofilm disassembly. Science. 2010 Apr 30;328(5978):627–9.
  35. Romero D, Aguilar C, Losick R, Kolter R. Amyloid fibers provide structural integrity to Bacillus subtilis biofilms. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2230–4.
  36. Schaub RE, Dillard JP. The Pathogenic Neisseria Use a Streamlined Set of Peptidoglycan Degradation Proteins for Peptidoglycan Remodeling, Recycling, and Toxic Fragment Release. Front Microbiol. 2019;10:73.
  37. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988 Feb 1;22(2):191–203.
  38. Fissore A, Marengo M, Santoro V, Grillo G, Oliaro-Bosso S, Cravotto G, et al. Extraction and Characterization of Bromelain from Pineapple Core: A Strategy for Pineapple Waste Valorization. Processes. 2023 Jul;11(7):2064.
  39. Gautam SS, K. S, Dash V, Goyal AK, Rath G. Comparative study of extraction, purification and estimation of bromelain from stem and fruit of pineapple plant. Thai J Pharm Sci. 2010 Jan 1;34(2):67–76.
  40. Hatano K ichi, Takahashi K, Tanokura M. Bromein, a Bromelain Inhibitor from Pineapple Stem: Structural and Functional Characteristics. Protein Pept Lett. 25(9):838–52.
  41. Rowan A, Buttle D, Barrett A. The cysteine proteinases of the pineapple plant. Biochem J. 1990 Apr 1;266:869–75.
  42. Novaes LCL, Jozala AF, Mazzola P, Pessoa A. The influence of pH, polyethylene glycol and polyacrylic acid on the stability of stem bromelain. Braz J Pharm Sci. 2014;50(2):371–80. doi:10.1590/S1984-82502014000200017.
  43. Devakate RV, Patil VV, Waje SS, Thorat BN. Purification and drying of bromelain. Sep Purif Technol. 2009 Jan 12;64(3):259–64.
  44. Bianca Martins, Robson Rescolino, Diego De Freitas Coelho, Foued Espindola, Beatriz Zanchetta, Elias Basile Tambourgi, et al. Characterization of bromelain from ananas comosus agroindustrial residues purified by ethanol factional precipitation. Chem Eng Trans. 2014;37:781–6.
  45. Vejai Vekaash CJ, Kumar Reddy TV, Venkatesh KV. Effect of vital bleaching with solutions containing different concentrations of hydrogen peroxide and pineapple extract as an additive on human enamel using reflectance spectrophotometer: An: in vitro: study. J Conserv Dent Endod. 2017 Oct;20(5):337.
  46. AlSheikh HMA, Sultan I, Kumar V, Rather IA, Al-Sheikh H, Tasleem Jan A, et al. Plant-Based Phytochemicals as Possible Alternative to Antibiotics in Combating Bacterial Drug Resistance. Antibiotics. 2020 Aug 4;9(8):480.
  47. Ryan RE. A double-blind clinical evaluation of bromelains in the treatment of acute sinusitis. Headache. 1967;7(1):13–7.
  48. Castell JV, Friedrich G, Kuhn CS, Poppe GE. Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake. Am J Physiol-Gastrointest Liver Physiol. 1997 Jul;273(1):G139–46.
  49. Chandwani ND, Maurya N, Nikhade P, Chandwani J. Comparative evaluation of antimicrobial efficacy of calcium hydroxide, triple antibiotic paste and bromelain against Enterococcus faecalis: An: In Vitro: study. J Conserv Dent Endod. 2022 Feb;25(1):63.
  50. 50.            Varilla C, Marcone M, Paiva L, Baptista J. Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary. Foods. 2021 Sep 23;10(10):2249.
  51. O.v O, F.l O, B.i O, D.m S, M DV. Exploring the Therapeutic Potential of Bromelain from Pineapple Fruit Peel: Enzymatic Activity and Antibiotic Synergy. Int J Biochem Res Rev. 2025 May 6;34(3):118–27.
  52. Silva MP, Calomino MA, Teixeira LA, Barros RR, de Paula GR, Teixeira FL. Antibiofilm activity of bromelain from pineapple against Staphylococcus aureus. Acta Sci Biol Sci. 2023;45:e65725.
  53. Shoham Y, Krieger Y, Tamir E, Silberstein E, Bogdanov?Berezovsky A, Haik J, et al. Bromelain?based enzymatic debridement of chronic wounds: A preliminary report. Int Wound J. 2018 Apr 25;15(5):769–75.
  54. Bayat S, Zabihi AR, Farzad SA, Movaffagh J, Hashemi E, Arabzadeh S, Hashemi M. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021;24(10):1404–12.
  55. Bayat S, Rabbani Zabihi A, Amel Farzad S, Movaffagh J, Hashemi E, Arabzadeh S, et al. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021 Oct;24(10):1404–12.
  56. Shoham Y, Krieger Y, Tamir E, Silberstein E, Bogdanov-Berezovsky A, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: A preliminary report. Int Wound J. 2018;15(5):769–75. doi:10.1111/iwj.12925. PMID: 29696785; PMCID: PMC7950085.
  57. Carter CJ, Pillai K, Badar S, Mekkawy AH, Akhter J, Jefferies T, Valle SJ, Morris DL. Dissolutionof biofilm secreted by three different strains of Pseudomonas aeruginosa with bromelain, N-acetylcysteine, and their combinations. Appl Sci. 2021;11(23):11388.
  58. Amante C, De Soricellis C, Luccheo G, Luccheo L, Russo P, Aquino RP, et al. Flogomicina: A Natural Antioxidant Mixture as an Alternative Strategy to Reduce Biofilm Formation. Life. 2023 Apr;13(4):1005.
  59. Pompilio A, Riviello A, Crocetta V, Di Giuseppe F, Pomponio S, Sulpizio M, et al. Evaluation of antibacterial and antibiofilm mechanisms by usnic acid against methicillin-resistant Staphylococcus aureus. Future Microbiol. 2016 Oct;11:1315–38.
  60. Morroni G, Alvarez-Suarez JM, Brenciani A, Simoni S, Fioriti S, Pugnaloni A, et al. Comparison of the Antimicrobial Activities of Four Honeys From Three Countries (New Zealand, Cuba, and Kenya). Front Microbiol. 2018;9:1378.
  61. Francisconi RS, Huacho PMM, Tonon CC, Bordini EAF, Correia MF, Sardi J de CO, et al. Antibiofilm efficacy of tea tree oil and of its main component terpinen-4-ol against Candida albicans. Braz Oral Res. 2020 Jun 5;34:e050.
  62. Long J, Yang C, Liu J, Ma C, Jiao M, Hu H, et al. Tannic acid inhibits Escherichia coli biofilm formation and underlying molecular mechanisms: Biofilm regulator CsgD. Biomed Pharmacother. 2024 Jun 1;175:116716.
  63. Fleming D, Chahin L, Rumbaugh K. Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds. Antimicrob Agents Chemother. 2017 Feb;61(2):e01998-16.

Photo
Twinkle N. U.
Corresponding author

College of Pharmaceutical Sciences, GMC, Kannur, 670503.

Photo
Shijith K. V.
Co-author

College of Pharmaceutical Sciences, GMC, Kannur, 670503.

Photo
Ansira P.
Co-author

College of Pharmaceutical Sciences, GMC, Kannur, 670503.

Photo
Arya P. V.
Co-author

College of Pharmaceutical Sciences, GMC, Kannur, 670503.

Photo
Baby Nishma
Co-author

College of Pharmaceutical Sciences, GMC, Kannur, 670503.

Twinkle N. U., Shijith K. V., Ansira P., Arya P. V., Baby Nishma, Targeting Wound Biofilms: Biofilm Formation, Resistance, and Natural Antibiofilm Strategies, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 7, 3136-3150. https://doi.org/10.5281/zenodo.16356613

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