Antimicrobial polymer-loaded hydrogels for the topical treatment of multidrug-resistant wound biofilm infections

Makabenta, Jessa Marie V.; Nabawy, Ahmed; Chattopadhyay, Aritra Nath; Jeon, Taewon; Park, Jungmi; Lo, Pui Chi; Nosovitski, Stas; Huang, Rui; Li, Cheng-Hsuan; Jiang, Mingdi; Rotello, Vincent M.

doi:10.1016/j.jconrel.2023.09.002

Cited by 4 publications

(2 citation statements)

References 52 publications

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“…Besides delivering AMPs, PLGA NPs serve as a lactate supply, which has been associated with accelerated angiogenesis and recruitment of endothelial progenitor cells and enhanced wound healing process [137]. Also, the incorporation of potent cationic antimicrobial polymers into neutral hydrogels that protect the wound and conditions advantageous to wound healing showed to be a promising and clinically translatable strategy to treat resilient wound biofilm infections [138].…”

Section: Biofilm Wound Treatmentmentioning

confidence: 99%

Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches

Cavallo,

Sivori,

Mastrofrancesco

et al. 2024

Biology

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Wound repair and skin regeneration is a very complex orchestrated process that is generally composed of four phases: hemostasis, inflammation, proliferation, and remodeling. Each phase involves the activation of different cells and the production of various cytokines, chemokines, and other inflammatory mediators affecting the immune response. The microbial skin composition plays an important role in wound healing. Indeed, skin commensals are essential in the maintenance of the epidermal barrier function, regulation of the host immune response, and protection from invading pathogenic microorganisms. Chronic wounds are common and are considered a major public health problem due to their difficult-to-treat features and their frequent association with challenging chronic infections. These infections can be very tough to manage due to the ability of some bacteria to produce multicellular structures encapsulated into a matrix called biofilms. The bacterial species contained in the biofilm are often different, as is their capability to influence the healing of chronic wounds. Biofilms are, in fact, often tolerant and resistant to antibiotics and antiseptics, leading to the failure of treatment. For these reasons, biofilms impede appropriate treatment and, consequently, prolong the wound healing period. Hence, there is an urgent necessity to deepen the knowledge of the pathophysiology of delayed wound healing and to develop more effective therapeutic approaches able to restore tissue damage. This work covers the wound-healing process and the pathogenesis of chronic wounds infected by biofilm-forming pathogens. An overview of the strategies to counteract biofilm formation or to destroy existing biofilms is also provided.

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Section: Biofilm Wound Treatmentmentioning

confidence: 99%

Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches

Cavallo,

Sivori,

Mastrofrancesco

et al. 2024

Biology

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“…While there are indeed articles that elucidate the complex interaction between wound healing and biofilm formation, it is surprising that experimental and in vivo wound models that investigate the effects of cellular therapies on wound healing often do not include the consideration of biofilm formation and presence. Therefore, future research is warranted to decipher the bio-pathological mechanisms of biofilm formation in wound beds [ 128 – 131 ]. This lack of consideration may in part explain why promising pre-clinical studies often do not successfully translate into meaningful clinical data.…”

Section: Biofilmsmentioning

confidence: 99%

Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

Huelsboemer,

Knoedler,

Kochen

et al. 2024

Military Med Res

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Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

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Engineered Bacteriophage-Polymer Nanoassemblies for Treatment of Wound Biofilm Infections

Park,

Hassan,

Nabawy

et al. 2024

ACS Nano

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The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of Staphylococcus aureus, including methicillinresistant S. aureus (MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log 10 bacterial reduction (∼99.9%) against MRSA biofilms in vitro. PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto in vivo wound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log 10 reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.

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Antimicrobial polymer-loaded hydrogels for the topical treatment of multidrug-resistant wound biofilm infections

Cited by 4 publications

References 52 publications

Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches

Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches

Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

Engineered Bacteriophage-Polymer Nanoassemblies for Treatment of Wound Biofilm Infections

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