Objective: This study demonstrates the impact of alterations in pressure, vascular compliance, arterial pulsatility, and autoregulation on tissue perfusion following middle cerebral artery (MCA) occlusion using mathematical modeling. Methods: Our previous mathematical model of the cerebral circulation is expanded to include vessel compliance and pulsatility of blood flow. An experimentally-obtained pressure waveform is used as an incoming boundary condition to simulate the effects of vascular compliance and pulsatility of flow on perfusion following MCA occlusion. The waveform is adjusted to model the effects of elevated mean arterial pressure. Results: Increased distensibility reduces the amplitude of oscillations in the time-dependent pressure solutions, whereas decreased distensibility produces more variation in these pressures. Occlusion significantly alters the magnitude of flow changes when incoming pressure is varied. The addition of the pulsatile pressure boundary condition and capacitances in the arteries and veins shifts the autoregulation plateau to higher pressures. Conclusions: This study reveals how changes in incoming pressure affect compensatory responses to ischemic stroke caused by MCA occlusion. Boundary conditions corresponding to elevated mean arterial pressures are associated with lower degrees of ischemia, an improvement that is supported by changes in autoregulation patterns following occlusion. The results also demonstrate how increases in arterial stiffness associated with aging can inhibit the ability of the vasculature to accommodate pulsatile flow by analyzing resulting patterns such as larger amplitudes of pressure and flow oscillations in the microcirculation. The study provides a foundation for modeling the relationships among vessel compliance, arterial blood pressure, and cerebrovascular conditions.

BACKGROUND:Diabetic foot ulcers (DFUs) remain one of the most devastating complications of diabetes, accounting for over 80% of nontraumatic amputations and contributing to a 5-year mortality rate exceeding 30%. Despite significant clinical advances, profound disparities persist. Racial and ethnic minoritized populations, rural communities, and people with low socioeconomic resources experience disproportionate rates of severe ulceration, infection, delayed healing, and amputation. PROBLEM:Traditional research approaches, often developed in academic settings without community input, have insufficiently addressed the contextual, cultural, and structural factors shaping DFU risk and outcomes. APPROACH:Community-engaged research (CEnR) offers a promising pathway to address these inequities; yet, DFU-specific evidence remains limited and heterogeneous. In response, the Diabetic Foot Consortium (DFC), a national research network funded by the National Institute of Diabetes and Digestive and Kidney Diseases, has initiated multisite efforts to embed community advisory boards, faith-based partnerships, mobile outreach, and culturally aligned engagement into DFU research. MODEL:We propose the DFC-CEnR Model, a conceptual framework for integrating community-engaged approaches to DFU prevention, early detection, treatment, and research participation. The model distinguishes CEnR from related approaches (community-based participatory research, patient and public involvement, cultural humility, and equity-focused system interventions), outlining hypothesized mechanisms and evaluation domains. Illustrative consortium examples demonstrate how engagement domains may be operationalized and inform future testing of validated outcome measures. IMPLICATIONS:This article positions community engagement as a hypothesis-generating strategy that requires rigorous empirical testing to determine its impact on DFU outcomes and disparities.

Wound healing emerges from a tightly orchestrated bioelectric landscape shaped by ion gradients, membrane potentials, and redox dynamics physical cues that direct cell migration, immune activation, and epithelial organization long before biochemical gradients take form. Recent advances reveal that electrical signals constitute a master regulatory layer: Transient receptor potential (TRP)-channel mediated ion flux governs early wound polarity; endogenous transepithelial potential collapse triggers rapid electric fields that guide keratinocyte and fibroblast migration; and connexin-dependent gap-junction coupling coordinates tissue-level responses across multicellular sheets. Electroceutical strategies exploit these principles by recalibrating electrical and electrochemical environments rather than targeting single molecules. This shift enables simultaneous modulation of ion-channel gating, cytoskeletal dynamics, growth-factor signaling, and immunometabolic programs reshaping whole-tissue behavior in ways unattainable with classical pharmacology. Key breakthroughs demonstrate that controlled electrical stimulation can reprogram human macrophages toward reparative phenotypes, enhance keratinocyte electrotaxis even under diabetic conditions, accelerate fibroblast-driven matrix assembly, and amplify endothelial angiogenic responses. Microbial communities respond in the opposite direction. Biofilms, long considered antibiotic-impervious, depend on exquisitely tuned membrane potential, proton motive force, and redox stratification for cohesion and persistence. Low-intensity electrical cues disrupt this energetics, collapsing efflux pump function, silencing quorum systems, loosening EPS architecture, and destabilizing metabolic heterogeneity effects impossible to escape through single gene mutation. Overall, these discoveries frame electroceuticals as system-level disruptors of microbial order and restorers of host coordination. With the emergence of AI-enabled, closed-loop bioelectronic dressings capable of sensing and responding to wound physiology in real time, electricity is poised to become a foundational operating principle for next-generation regenerative and anti-infective therapy.

OBJECTIVE:Use a new patient registry to characterize and predict progression of lower-extremity chronic wounds to amputation and/or death, while considering infection history. BACKGROUND:Chronic wounds are a common health issue causing amputation and death. The Regenstrief Chronic Wound Registry, created from one of the U.S.'s largest health information exchanges, can give insights into their epidemiology. METHODS:This retrospective cohort study analyzed 52,916 patients first diagnosed with lower-extremity chronic wounds during 2011-2021, sourced from the registry of 152,237 chronic wound patients. Disease progression was modeled using a multistate model, tracking transitions from initial diagnosis to minor amputation, major amputation, and/or death. Cox proportional-hazards models assessed associations between time-dependent covariates, including infection history and wound type, and each state transition. RESULTS:Three-year pooled mortality rates after wound diagnosis, minor amputation, and major amputation were 10.71%, 13.38%, and 19.47%, respectively. The multistate model showed these associations: diabetic foot ulcer and increased minor amputation; venous ulcer and decreased amputation or death; pressure ulcer, decreased minor amputation, and increased death; osteomyelitis, increased amputation, and decreased death before major amputation; sepsis and increased death before major amputation. Simulated patients' individualized risks were estimated-e.g., probabilities of major amputation for diabetic White patients within three years after minor amputation, with and without prior osteomyelitis diagnosis, were 3.7% and 14.9% respectively. CONCLUSIONS:A multistate model, applied to a state-wide chronic wound patient registry, reveals insights into chronic wound disease progression, enables personalized prognoses for patients with chronic wounds, and has the potential to improve clinical decision-making.

Use a new patient registry to characterize and predict progression of lower-extremity chronic wounds to amputation and/or death, while considering infection history. Chronic wounds are a common health issue causing amputation and death. The Regenstrief Chronic Wound Registry, created from one of the U.S.’s largest health information exchanges, can give insights into their epidemiology. This retrospective cohort study analyzed 52,916 patients first diagnosed with lower-extremity chronic wounds during 2011–2021, sourced from the registry of 152,237 chronic wound patients. Disease progression was modeled using a multistate model, tracking transitions from initial diagnosis to minor amputation, major amputation, and/or death. Cox proportional-hazards models assessed associations between time-dependent covariates, including infection history and wound type, and each state transition. Three-year pooled mortality rates after wound diagnosis, minor amputation, and major amputation were 10.71%, 13.38%, and 19.47%, respectively. The multistate model showed these associations: diabetic foot ulcer and increased minor amputation; venous ulcer and decreased amputation or death; pressure ulcer, decreased minor amputation, and increased death; osteomyelitis, increased amputation, and decreased death before major amputation; sepsis and increased death before major amputation. Simulated patients’ individualized risks were estimated—e.g., probabilities of major amputation for diabetic White patients within three years after minor amputation, with and without prior osteomyelitis diagnosis, were 3.7% and 14.9% respectively. A multistate model, applied to a state-wide chronic wound patient registry, reveals insights into chronic wound disease progression, enables personalized prognoses for patients with chronic wounds, and has the potential to improve clinical decision-making.

OBJECTIVE:The National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Foot Consortium tested the hypothesis that compromised restoration of the skin barrier function of closed diabetic foot ulcers (DFUs), as measured by high transepidermal water loss (TEWL), is associated with an increased risk of DFU recurrence. RESEARCH DESIGN AND METHODS:This was a multicenter noninterventional study measuring TEWL in 418 adult participants with diabetes and a recently healed DFU. TEWL was measured at the center of the closed wound and at an anatomically similar reference area on the contralateral foot within 2 weeks of wound closure (visit 1); measurements were repeated at a wound closure confirmation visit 2 weeks later (visit 2). Participants were observed for up to 16 weeks to assess for wound recurrence. Participant self-reported and clinician assessments of DFU wound recurrence were recorded. RESULTS:DFU recurrence by week 16 occurred in 21.5% of participants. Mean TEWL at the center of the healed DFU at visit 1 was higher for those with recurrence compared with those without (P = 0.006). Among participants with high TEWL (>30.05 g · m-2 · h-1), 35% reported wound recurrence by 16 weeks versus 17% of those with low TEWL. The odds ratio for recurrence for participants with high TEWL was 2.66 (P < 0.001). Self-reported wound recurrence was highly concordant with clinician assessment of wound recurrence. CONCLUSIONS:Compromised wound healing mechanisms culminating in wound closure associated with defective skin barrier function is associated with increased risk of DFU recurrence. Measurement of TEWL has value as a predictor of functional wound healing and could affect clinical practice, leading to better outcomes.

Significant knowledge gaps exist regarding the responses of cells, tissues, and organs to organismal death. Examining the survival mechanisms influenced by metabolism and environment, this research has the potential to transform regenerative medicine, redefine legal death, and provide insights into life’s physiological limits, paralleling inquiries in embryogenesis.

OBJECTIVE:An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. METHODS:The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. RESULTS:An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. CONCLUSIONS:This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m(-2).h(-1) (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

Wound trajectory and outcomes research has applications in different aspects of wound healing: forecasting wound healing time, access and utilization of wound care services, factors associated with disparities in wound care services, and its quality and outcomes. Wound care research benefits from a well-maintained record management system. In this article, we demonstrate the customization of the District Health Information Software (DHIS2) platform to integrate wound care clinical data with social determinants of health from several Comprehensive Wound Centers (CWC) in Indiana. We describe the modules and features of our platform, such as tracker capture, visualization, and maps. DHIS2 is used in more than 60 countries to monitor and evaluate health programs. However, to the best of our knowledge, this is the first attempt to use DHIS2 as a wound care data warehouse, a platform to perform wound care research for academic researchers and clinical practitioners. Clinicians can use the platform as one of the key tools to make an informed decision in determining the treatment for favorable healing trajectory and wound outcomes. We conducted a usability and acceptance survey among researchers at the Indiana Center for Regenerative Medicine and Engineering and found that DHIS2 can be a suitable infrastructure to manage metadata to import and analyze combined data from disparate sources, including Electronic Medical Records, WoundExpert, and clinical trials management software like REDCap.

Repair of epithelial defect is complicated by infection and related metabolites. Pyocyanin (PYO) is one such metabolite that is secreted during Pseudomonas aeruginosa infection. Keratinocyte (KC) migration is required for the closure of skin epithelial defects. This work sought to understand PYO-KC interaction and its significance in tissue repair. Stable Isotope Labeling by Amino acids in Cell culture proteomics identified mitochondrial dysfunction as the top pathway responsive to PYO exposure in human KCs. Consistently, functional studies showed mitochondrial stress, depletion of reducing equivalents, and adenosine triphosphate. Strikingly, despite all stated earlier, PYO markedly accelerated KC migration. Investigation of underlying mechanisms revealed, to our knowledge, a previously unreported function of keratin 6A in KCs. Keratin 6A was PYO inducible and accelerated closure of epithelial defect. Acceleration of closure was associated with poor quality healing, including compromised expression of apical junction proteins. This work recognizes keratin 6A for its role in enhancing KC migration under conditions of threat posed by PYO. Qualitatively deficient junctional proteins under conditions of defensive acceleration of KC migration explain why an infected wound close with deficient skin barrier function as previously reported.

Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression (GTEx) database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such as FOXO1 , FOXO3 , ATF4 and CEBPD . Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. In addition, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix (collagen expression and metabolism). Efforts to understand the significance of death as a biological variable (DABV) in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the involvement of the host immune system. Iterative changes in the host and pathogen during the formation of such clinically relevant biofilm can only occur in vivo. The swine wound model is recognized for its advantages as a powerful pre-clinical model. There are several reported approaches for studying wound biofilms. In vitro and ex vivo systems are deficient in terms of the host immune response. Short-term in vivo studies involve acute responses and, thus, do not allow for biofilm maturation, as is known to occur clinically. The first long-term swine wound biofilm study was reported in 2014. The study recognized that biofilm-infected wounds may close as determined by planimetry, but the skin barrier function of the affected site may fail to be restored. Later, this observation was validated clinically. The concept of functional wound closure was thus born. Wounds closed but deficient in skin barrier function may be viewed as invisible wounds. In this work, we seek to report the methodological details necessary to reproduce the long-term swine model of biofilm-infected severe burn injury, which is clinically relevant and has translational value. This protocol provides detailed guidance on establishing an 8 week wound biofilm infection using P. aeruginosa (PA01). Eight full-thickness burn wounds were created symmetrically on the dorsum of domestic white pigs, which were inoculated with (PA01) at day 3 post-burn; subsequently, noninvasive assessments of the wound healing were conducted at different time points using laser speckle imaging (LSI), high-resolution ultrasound (HUSD), and transepidermal water loss (TEWL). The inoculated burn wounds were covered with a four-layer dressing. Biofilms, as established and confirmed structurally by SEM at day 7 post-inoculation, compromised the functional wound closure. Such an adverse outcome is subject to reversal in response to appropriate interventions.

Biofilm infection is a major contributor to wound chronicity. The establishment of clinically relevant experimental wound biofilm infection requires the involvement of the host immune system. Iterative changes in the host and pathogen during the formation of such clinically relevant biofilm can only occur in vivo. The swine wound model is recognized for its advantages as a powerful pre-clinical model. There are several reported approaches for studying wound biofilms. In vitro and ex vivo systems are deficient in terms of the host immune response. Short-term in vivo studies involve acute responses and, thus, do not allow for biofilm maturation, as is known to occur clinically. The first long-term swine wound biofilm study was reported in 2014. The study recognized that biofilm-infected wounds may close as determined by planimetry, but the skin barrier function of the affected site may fail to be restored. Later, this observation was validated clinically. The concept of functional wound closure was thus born. Wounds closed but deficient in skin barrier function may be viewed as invisible wounds. In this work, we seek to report the methodological details necessary to reproduce the long-term swine model of biofilm-infected severe burn injury, which is clinically relevant and has translational value. This protocol provides detailed guidance on establishing an 8 week wound biofilm infection using P. aeruginosa (PA01). Eight full-thickness burn wounds were created symmetrically on the dorsum of domestic white pigs, which were inoculated with (PA01) at day 3 post-burn; subsequently, noninvasive assessments of the wound healing were conducted at different time points using laser speckle imaging (LSI), high-resolution ultrasound (HUSD), and transepidermal water loss (TEWL). The inoculated burn wounds were covered with a four-layer dressing. Biofilms, as established and confirmed structurally by SEM at day 7 post-inoculation, compromised the functional wound closure. Such an adverse outcome is subject to reversal in response to appropriate interventions.

Objective: Despite advances in the use of topical and parenteral antimicrobial therapy and the practice of early tangential burn wound excision to manage bacterial load, 60% of the mortality from burns is attributed to bacterial biofilm infection. A low electric field (∼1 V) generated by the novel FDA-cleared wireless electroceutical dressing (WED) was previously shown to significantly prevent and disrupt burn biofilm infection in preclinical studies. Based on this observation, the purpose of this clinical trial was to evaluate the efficacy of the WED dressing powered by a silver-zinc electrocouple in the prevention and disruption of biofilm infection. Approach: A prospective, randomized, controlled, single-center clinical trial was performed to evaluate the efficacy of the WED compared with standard-of-care (SoC) dressing to treat biofilms. Burn wounds were randomized to receive either SoC or WED. Biopsies were collected on days 0 and 7 for histology, scanning electron microscopy (SEM) examination of biofilm, and for quantitative bacteriological analyses. Results: In total, 38 subjects were enrolled in the study. In 52% of the WED-treated wounds, little to no biofilm could be detected by SEM. WED significantly lowered or prevented increase of biofilm in all wounds compared with the pair-matched SoC-treated wounds. Innovation: WED is a simple, easy, and rapid method to protect the wound while also inhibiting infection. It is activated by a moist environment and the electrical field induces transient and micromolar amounts of superoxide anion radicals that will prevent bacterial growth. Conclusion: WED decreased biofilm infection better compared with SoC. The study was registered in clinicaltrials.gov as NCT04079998.

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5′-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.

LEARNING OBJECTIVES:After studying this article, the participant should be able to: 1. Understand the basics of biofilm infection and be able to distinguish between planktonic and biofilm modes of growth. 2. Have a working knowledge of conventional and emerging antibiofilm therapies and their modes of action as they pertain to wound care. 3. Understand the challenges associated with testing and marketing antibiofilm strategies and the context within which these strategies may have effective value.SUMMARY:The Centers for Disease Control and Prevention estimate for human infectious diseases caused by bacteria with a biofilm phenotype is 65 percent and the National Institutes of Health estimate is closer to 80 percent. Biofilms are hostile microbial aggregates because, within their polymeric matrix cocoons, they are protected from antimicrobial therapy and attack from host defenses. Biofilm-infected wounds, even when closed, show functional deficits such as deficient extracellular matrix and impaired barrier function, which are likely to cause wound recidivism. The management of invasive wound infection often includes systemic antimicrobial therapy in combination with débridement of wounds to a healthy tissue bed as determined by the surgeon who has no way of visualizing the biofilm. The exceedingly high incidence of false-negative cultures for bacteria in a biofilm state leads to missed diagnoses of wound infection. The use of topical and parenteral antimicrobial therapy without wound débridement have had limited impact on decreasing biofilm infection, which remains a major problem in wound care. Current claims to manage wound biofilm infection rest on limited early-stage data. In most cases, such data originate from limited experimental systems that lack host immune defense. In making decisions on the choice of commercial products to manage wound biofilm infection, it is important to critically appreciate the mechanism of action and significance of the relevant experimental system. In this work, the authors critically review different categories of antibiofilm products, with emphasis on their strengths and limitations as evident from the published literature.