Dual-Action Healing: How Chitosan Combats Bacteria and Accelerates Wound Recovery

Professional wound care in action: Advanced chitosan-based dressings provide dual-action protection through antimicrobial defence and accelerated tissue regeneration.

Chronic and infected wounds pose significant healthcare challenges, often leading to prolonged suffering, substantial costs, and severe outcomes including amputation and mortality. The intersection of bacterial infection and impaired tissue regeneration creates a vicious cycle perpetuating wound chronicity. Chitosan, a naturally derived biopolymer, has emerged as a uniquely promising therapeutic candidate, offering a sophisticated dual-action mechanism that simultaneously combats bacterial invasion whilst accelerating wound recovery. This article examines chitosan's antimicrobial properties, regenerative capabilities, and clinical applications in advanced wound care, particularly for chronic and diabetic wounds where conventional therapies frequently fail. Our previous discussions on chitosan-based wound dressings have highlighted its exceptional versatility [Link to Previous Article: "Chitosan-Based Wound Dressings: Improving Healing and Preventing Amputations"].

Chitosan: Structure and Dual-Action Properties

Chitosan is a linear polysaccharide derived from chitin deacetylation, comprising β-(1→4)-linked D-glucosamine and N-acetyl-D-glucosamine residues. This unique structure endows chitosan with exceptional physicochemical and biological properties ideally suited for biomedical applications (Rajkumar et al., 2024; Matica et al., 2019). The polycationic nature arising from amino group protonation represents the cornerstone of its biological functionality, facilitating electrostatic interactions with bacterial membranes, extracellular matrix components, and growth factors (Dai et al., 2011; Guarnieri et al., 2022). Chitosan exhibits remarkable biocompatibility and biodegradability, degrading enzymatically into non-toxic oligosaccharides readily metabolised or incorporated into glycosaminoglycans (Singh et al., 2017; Molaei et al., 2025).

Antimicrobial Mechanisms: Combating Infection

Chitosan's potent antimicrobial activity provides critical protection against bacterial colonisation through multiple synergistic mechanisms.

Microscopic view of bacterial cells: Chitosan's cationic charge enables electrostatic interaction with bacterial membranes, disrupting cell wall integrity and preventing infection in wound sites.

Bacterial Membrane Disruption: The primary mechanism involves electrostatic interactions between chitosan's positively charged amino groups and negatively charged bacterial cell surface components. In Gram-negative bacteria, chitosan interacts with lipopolysaccharides, whilst in Gram-positive bacteria, it binds teichoic acids and peptidoglycans (Guarnieri et al., 2022; Raafat et al., 2008). These interactions disrupt membrane integrity, causing potassium efflux, membrane depolarisation, and leakage of intracellular contents (Raafat et al., 2008; Hemmingsen et al., 2022). Electron microscopy studies reveal visible membrane perforation and pore formation, with damage correlating to chitosan concentration and deacetylation degree (Younes et al., 2017; Kim et al., 2020).

Intracellular Effects: Low molecular weight chitosan oligomers penetrate disrupted membranes, interacting with DNA and RNA to interfere with transcription and translation (Dai et al., 2011; Raafat et al., 2008). Chitosan also chelates essential metal ions and inhibits bacterial enzymes, disrupting metabolic pathways (Guarnieri et al., 2022). Furthermore, chitosan induces oxidative stress by generating reactive oxygen species (ROS), overwhelming bacterial antioxidant defences and causing protein oxidation, lipid peroxidation, and DNA damage (Kim et al., 2020; Hemmingsen et al., 2022).

Biofilm Prevention: Biofilms represent formidable obstacles in chronic wound healing. Chitosan demonstrates remarkable efficacy in preventing biofilm formation and disrupting established biofilms (Yang et al., 2021; Patil et al., 2023). It interferes with bacterial adhesion, penetrates the extracellular polymeric substance matrix, disrupts quorum sensing, and induces bacterial cell death (Yang et al., 2021; Molaei et al., 2025). Studies demonstrate chitosan-based formulations reduce pathogenic biofilm formation by up to 90% (Patil et al., 2023; Hemmingsen et al., 2022).

Wound Healing Acceleration: Regenerative Action

Chitosan's regenerative capabilities accelerate wound healing through modulation of haemostasis, inflammation, proliferation, and remodelling phases.

Chitosan-based dressings accelerate healing through haemostasis, immune modulation, cellular proliferation, and enhanced angiogenesis.

Haemostasis: Chitosan functions as a potent haemostatic agent, initiating rapid blood coagulation through electrostatic attraction and aggregation of erythrocytes and platelets (Lee et al., 2024; Gheorghiță et al., 2023). Groundbreaking research by Lee et al. (2024) revealed chitosan directly activates platelets through Toll-like receptor 2 (TLR2) signalling, inducing calcium influx and integrin activation. This TLR2-mediated pathway remains effective even with anticoagulant and antiplatelet therapies.

Immune Modulation: Chitosan orchestrates balanced inflammatory responses crucial for optimal healing. It promotes transition from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, essential for progression to the proliferative phase (Vasconcelos et al., 2015; Maita et al., 2022). Chitosan suppresses pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) whilst upregulating anti-inflammatory mediators (IL-10, TGF-β), fostering pro-regenerative microenvironments (Mohandas et al., 2025; Feng et al., 2021). Yang et al. (2021) developed ROS-eliminating carboxymethyl chitosan hydrogels that dramatically accelerated burn healing by reducing oxidative damage.

Cellular Proliferation and Angiogenesis: Chitosan stimulates proliferation and migration of fibroblasts, keratinocytes, and endothelial cells. Howling et al. (2001) demonstrated highly deacetylated chitosan increased fibroblast proliferation rates by approximately 50%, upregulating collagen types I and III production (Feng et al., 2021; Loo et al., 2022). Chitosan promotes angiogenesis by enhancing vascular endothelial growth factor (VEGF) production and activity (Mohandas et al., 2015; Vijayan et al., 2019). Studies confirm chitosan scaffolds significantly increase blood vessel density and accelerate healing in diabetic models (Vijayan et al., 2019).

ECM Remodelling: Chitosan facilitates organised collagen deposition and extracellular matrix remodelling, upregulating collagen types I and III genes and promoting strategic transition from provisional to mature collagen (Feng et al., 2021; Molaei et al., 2025). This regulated remodelling reduces scar formation and improves tissue quality through TGF-β/Smad and PI3K/Akt/mTOR pathway activation (Feng et al., 2021; Molaei et al., 2025).

Clinical Evidence

Clinical trials demonstrate chitosan gel achieving 92% wound area reduction, offering hope for patients facing amputation risk

Diabetic Foot Ulcers: The landmark CHITOWOUND randomised controlled trial by Slivnik et al. (2024) evaluated chitosan gel (ChitoCare) in treating non-healing diabetic foot ulcers. The ChitoCare group exhibited median 92.0% wound surface area reduction versus 37.0% in placebo (p=0.008), with 4.62-fold higher likelihood of achieving 75% closure (p=0.012) (Slivnik et al., 2024). Escárcega-Galaz et al. (2017) reported all patients treated with topical chitosan experienced infection resolution and healthy tissue development.

Burn Wounds: Hu et al. (2023) demonstrated chitosan-treated burn patients achieved significantly shorter healing time (19.53±2.74 versus 24.78±4.86 days, p=0.015), higher healing percentage at day 14 (65.00% versus 37.50%, p=0.014), and substantially lower infection rates. Importantly, chitosan groups showed significantly lower scar scores three months post-healing (6.00±0.98 versus 8.77±1.19, p=0.031), indicating superior tissue quality (Hu et al., 2023).

Chronic Refractory Wounds: Liu et al. (2022) found chitosan-based hydrocolloid dressings demonstrated significantly superior healing efficacy, reduced pain scores, and greater wound area reduction compared to controls (all p<0.05), with lower dressing change frequency and reduced treatment costs.

Sustainability: The Entoplast Advantage

Traditional crustacean-derived chitosan faces challenges including seasonal availability, potential allergenicity, and environmental concerns. Black Soldier Fly (Hermetia illucens)-derived chitosan presents a superior alternative characterised by sustainability, scalability, and consistent quality. These insects efficiently convert organic waste into valuable biomass with minimal ecological impact, whilst avoiding shellfish-associated allergenic proteins. Entoplast specialises in producing premium-quality chitin and chitosan from Black Soldier Flies, ensuring superior biomaterials for advanced wound care applications.

Conclusion

Chitosan represents a paradigm shift in wound care management, offering sophisticated dual-action mechanisms that simultaneously combat bacterial infection and accelerate tissue regeneration. The multifaceted antimicrobial properties—membrane disruption, intracellular damage, and biofilm prevention—provide robust protection against pathogens, including multidrug-resistant strains. Concurrently, chitosan's regenerative capabilities orchestrate coordinated healing responses expediting wound closure and enhancing tissue quality.

Clinical evidence in diabetic foot ulcers, burn wounds, and chronic refractory wounds substantiates chitosan's therapeutic efficacy and safety. As global chronic wound burdens escalate, driven by ageing populations and rising diabetes prevalence, effective multifunctional wound care solutions are imperative. Sustainably sourced chitosan from Black Soldier Flies represents an ideal biomaterial meeting this critical need.

Entoplast leads this transformative field, delivering the highest quality, sustainably sourced chitin and chitosan to partners worldwide. Our dedication to research, innovation, and environmental stewardship ensures scientists, academics, and industry professionals have access to superior biomaterials for groundbreaking work. We are not merely suppliers; we are collaborators in advancing healthcare solutions.

We invite researchers, clinicians, pharmaceutical companies, and investors to connect with Entoplast. Discover how our premium chitin and chitosan products can elevate your research, enhance your product lines, and contribute to a future where advanced wound care is accessible and effective for all. Partner with Entoplast to innovate, lead, and make lasting impact in medical and pharmaceutical sectors. Contact us today at hello@entoplast.com to discuss collaborations and explore investment opportunities in our cutting-edge chitosan solutions.