Wound infections pose a substantial clinical challenge and an escalating healthcare burden, further complicated by the rapid increase in multidrug-resistant bacteria. Antimicrobial peptides (AMPs) offer an alternative to conventional antibiotics, but their rapid degradation, hemolytic activity, and potential cytotoxicity complicate systemic delivery and can have negative impact on wound healing. Here we show a bacterial nanocellulose hyaluronan (BC-HA) hybrid hydrogel wound dressing functionalized with mesoporous silica nanoparticles (MSNs) for localized, enzyme responsive delivery of a sequence optimized antimicrobial peptide (SOAP) for treatment of infected wounds. The dressings provide moisture retention and excellent skin conformability while enabling infection-triggered AMP release by bacterial and host proteases. In vitro, SOAP-loaded dressings showed potent activity against clinical wound pathogens while remaining compatible with human primary dermal fibroblasts and keratinocytes. In a contaminated porcine wound model, the dressings significantly reduced bacterial load while accelerating wound re-epithelialization and epithelial maturation compared to the controls. By integrating a dual-function hydrogel that promotes healing and provides on-demand antimicrobial activity, critical limitations in the use of AMPs in wound care can be addressed, providing new possibilities to treat infected wounds.

Bacterial cellulose (BC) is a clinically established nanofibrillar wound dressing material that promotes healing by maintaining a moist and protected wound microenvironment. BC dressings can remain on wounds for extended periods, improving patient outcomes and reducing healthcare costs. However, BC lacks intrinsic antimicrobial properties, and infections in contaminated wounds remain a clinical concern, particularly in vulnerable patient populations. In this study, we present a benign and scalable self-assembly strategy to functionalize clinically used BC dressings with presynthesized colloidal silver nanoparticles (AgNPs) and antimicrobial peptides (C5), resulting in dual-action antimicrobial activity while preserving beneficial BC material properties. Colloidal AgNPs were efficiently adsorbed into the BC matrix by tailoring the interaction potential between the BC nanofibrils and the nanoparticles. Subsequent functionalization with C5 provided complementary antimicrobial mechanisms. The resulting dressings exhibited potent antimicrobial activity against Staphylococcus aureus, while maintaining high cytocompatibility with human primary keratinocytes and fibroblasts. By enabling tunable silver content, improved antimicrobial performance, and low cytotoxicity, the platform offers a promising route toward infection control in hard-to-heal wounds using clinically approved advanced BC dressings.

Since the start of the full-scale invasion of Ukraine by Russian forces in 2022, the war has been characterized by high attrition rates on both sides with hundreds of thousands killed and wounded. 1 2 Haemorrhage is the most common cause of shock in trauma patients, estimated to be responsible for half of preventable deaths. 3 4 To reduce the haemorrhage-related mortality, proper training is vital. To this end, the Tactical Combat Casualty Care curriculum advocates for the use of advanced medical simulators, task-trainers and manikins. 5 Recent publications classify Live Tissue Training (LTT) as a highly valued high-fidelity simulator. 6 The frequent use of heavy weapon systems, such as massed large-calibre artillery, has resulted in an increasing number of casualties displaying wound patterns caused by fragmentation from exploding ordinance. 1 8 Casualties presenting with catastrophic haemorrhages with multiple points of bleeding have increased in frequency. 1 8 9 Due to their size and anatomical location, the preferred treatment of these wounds is packing with gauze or haemostatic dressings. Today, no high-fidelity simulator comparable to live tissue exists for training wound-packing techniques in wounds with multiple points of bleeding. To improve training in the management of massive haemorrhages, the main aim of this project was to develop and validate a repeatable high-fidelity simulator used for skill-training in haemorrhage control using wound packing techniques in a wound with multiple bleeding points. The study was conducted during medical training courses at the Center for Disaster Medicine and Traumatology. All animal experiments were approved by the Regional Ethical Review Board (ID 16652–2020) and were performed in accordance with the guidelines established by the Medical Faculty at Linköping University, Sweden, and the European Convention on Animal Care. The study population consisted of attendees in LTT training (n = 51), divided into two groups based on their skill level (experts vs novices). The new simulator, Repeatable Exsanguination Simulator Using Live Tissue (RESULT), is an artificial artery constructed using readily available materials and implanted into anesthetized animal models. By using external blood (or other fluid) to create bleedings, training with RESULT has no impact on circulatory volume. RESULT was compared against two existing simulators, TrueClot and LTT with real bleedings on anesthetized animals. Parameters measured included evaluating participant performance (time to bleeding control), and validity and fidelity between the different simulators using questionnaires (1–7 Likert scales). Results were compared using two-way analysis of variance coupled with Šídák’s multiple comparisons tests. Numbers are reported as mean ± standard deviation. A p value < than 0.05 was considered statistically significant. Expert participants achieved bleeding control significantly faster in RESULT compared to novices (137±85 vs 207±119 seconds, p < 0.01; figure 1A). There were no significant differences between expert and novices using TrueClot or LTT. RESULT was considered more realistic (6.27±0.8 vs 3.76±1.1, p < 0.0001; figure 1B), more challenging (5.45±1.1 vs 3.43±1.3, p < 0.0001; figure 1C) and gave a more valuable training experience (6.64±0.7 vs 4.80±1.5, p < 0.0001; figure 1D) compared to TrueClot. RESULT was considered equally realistic (6.27±0.8 vs 6.65±0.81, p > 0.05; fig 1B) and challenging (5.45±1.1 vs 5.26±1.3, p > 0.05; fig 1C) as LTT. The value of the training experience with RESULT rated equal to LTT (6.64±0.7 vs 6.73±0.79, p > 0.05; figure 1D). Abstract A15 Figure 1 Graphs summarizing measured parameters. A: Time to achieved bleeding control comparing experts and novices using the three different simulators. B: Perceived realism of the different simulators.1–7 C: Perceived challenge of stopping simulated bleeding.1–7 D: Value of training using the three simulators.1–7* equals p < 0.05, **** equals p < 0.0001 The present study validates RESULT as a reusable high-fidelity simulator for skill training on wound packing techniques in wounds with multiple bleeding points. As revealed by comparing performance in experts and novices, a higher degree of medical experience results in significantly faster bleeding control (70 seconds difference on average), further illustrating the validity of the simulator. Quinn J, Panasenko Si, Leshchenko Y, Gumeniuk K, Onderková A, Stewart D, et al . Prehospital lessons from the war in ukraine: damage control resuscitation and surgery experiences from point of injury to role 2 . Mil Med [Internet]. 2024 Jan 23 [cited 2025 Jul 26]; 189 (1–2). Available from: https://pubmed.ncbi.nlm.nih.gov/37647607/ Institute for the Study of War [Internet]. [cited 2025 Jul 26]. Institute for the Study of War. Available from: http://dev-isw.bivings.com/ ACS Store [Internet]. [cited 2025 Jul 26]. ATLS ® Student Course Manual, 10th Edition. Available from: https://store.facs.org/atls-student-course-manual-10th-edition Eastridge Bj, Holcomb Jb, Shackelford S. Outcomes of traumatic hemorrhagic shock and the epidemiology of preventable death from injury. Transfusion (Paris) [Internet]. 2019 Apr [cited 2025 Jul 26];59(S2). Available from: https://pubmed.ncbi.nlm.nih.gov/30980749/ TCCC Combat Lifesaver [Internet]. [cited 2025 Jul 26]. Available from: https://www.naemt.org/education/trauma-education/naemt-tccc/tccc-cls-guidelines-and-curriculum Swain Cs, Cohen Hml, Helgesson G, Rickard Rf, Karlgren K. A Systematic review of live animal use as a simulation modality (‘live tissue training’) in the emergency management of trauma. J Surg Educ [Internet]. 2023 Sep [cited 2025 Jul 26]; 80 (9). Available from: https://pubmed.ncbi.nlm.nih.gov/37516576/ Mahoney A, Reade Mc, Moffat M. Experiences of medical practitioners in the Australian Defence Force on live tissue trauma training. BMJ Mil Health [Internet]. 2023 Apr [cited 2025 Jul 26]; 169 (2). Available from: https://pubmed.ncbi.nlm.nih.gov/33087539/ Epstein A, Lim R, Johannigman J, Fox Cj, Inaba K, Vercruysse Ga, et al . Putting medical boots on the ground: lessons from the war in ukraine and applications for future conflict with near-peer adversaries. J Am Coll Surg [Internet]. 2023 Aug 1 [cited 2025 Jul 26]; 23 7(2). Available from: https://pubmed.ncbi.nlm.nih.gov/37459197/ Onderková A, Quinn J, Meoli M, Taylor D, Nesterenko S, Schramm Jm, et al . Enhancing prehospital care during the conflict in Ukraine: NATO’s role in global health engagement. Mil Med [Internet]. 2025 Feb 27 [cited 2025 Jul 26]; 190 (3–4). Available from: https://pubmed.ncbi.nlm.nih.gov/39163204/

Wounds are highly prone to infection, which can delay healing and lead to severe complications such as gangrene and sepsis. Non-healing wounds significantly impact patients' physical and mental well-being and place a substantial financial burden on healthcare systems. Timely and effective treatment of wound infections is critical, but the rise of antibiotic-resistant pathogens complicates this process. In this study, we investigate a potent protease resistant antimicrobial peptide (AMP), PLNC8 αβ, for the treatment of wound infections and present a strategy for localized AMP delivery using functionalized advanced nanocellulose (NC) wound dressings. Two types of NC dressings were explored: bacterial cellulose (BC) and TEMPO-oxidized nanocellulose derived from wood powder (TC). In a porcine wound infection model, PLNC8 αβ exhibited high antimicrobial activity, successfully eradicating the infection while promoting wound re-epithelialization. To achieve controlled release of PLNC8 αβ from the NC dressings, the peptides were either physisorbed directly onto the nanofibrils or encapsulated within mesoporous silica nanoparticles (MSNs) that were incorporated into the dressings. The PLNC8 αβ functionalized dressings demonstrated low cytotoxicity toward human primary fibroblasts and keratinocytes. Both BC and TC dressings showed efficient contact inhibition of bacteria but were less effective in inhibiting bacteria in suspension. In contrast, MSN-functionalized dressings, displayed significantly enhanced peptide-loading and sustained release capacities, resulting in improved antimicrobial efficacy. These findings highlight the potential of PLNC8 αβ and PLNC8 αβ-functionalized nanocellulose wound dressings for the treatment of infected wounds, offering an effective alternative to conventional antibiotic therapies.

Wound infections result in delayed healing, morbidity, and increased risks of sepsis. Early detection of wound infections can facilitate treatment and reduce the need for the excessive use of antibiotics. Proteases are normally active during the healing process but are overexpressed during infection as part of the inflammatory response. Proteases are also produced by the bacteria infecting the wounds, making proteases a highly relevant biomarker for infection monitoring. Here, we show a fluorescence turn-on sensor for real-time monitoring of protease activity in advanced nanocellulose wound dressings for rapid detection of wound pathogens. Colloidal gold nanoparticles (AuNPs) were adsorbed on bacterial cellulose (BC) nanofibrils by using a carefully optimized self-assembly process. The AuNPs could either be homogeneously incorporated in BC dressings or 3D printed in wood-derived cellulose nanofiber (CNF) dressings using a BC-AuNP ink. The BC-adsorbed AuNPs were subsequently functionalized with fluorophore-labeled protease substrates. Cleavage of the substrates by proteases produced by the wound pathogens Staphylococcus aureus and Pseudomonas aeruginosa resulted in a significant increase in fluorescence that correlated with the growth phase of the bacteria. Wound dressing with integrated sensors for the detection of proteolytic activity can enable the sensitive and rapid detection of infections, allowing for optimization of treatment and reducing the risks of complications.

Mesoporous silica materials are promising carriers for antimicrobial peptides (AMPs), offering a versatile platform for combating bacterial infections. However, achieving high loading efficiency and controlled AMP release under physiological conditions remains a challenge. This study introduces a protein-capped mesoporous silica-based delivery system for treating topical bacterial infections. The system leverages elevated protease activity at infection sites to trigger the release of the sequence-optimized antimicrobial lipopeptide L-6-C5 (SOAP), facilitating efficient bacterial killing. SOAP was loaded into aminopropyl-functionalized SBA-15 mesoporous silica (amino-SBA-15) and capped with bovine serum albumin (BSA) or casein, forming amino-SBA-15-SOAP@protein. Protein adsorption prevented premature SOAP release while enabling protease-triggered delivery. BSA capping achieved 92.6 ± 0.2 % loading efficiency and enhanced peptide retention by 4.5-fold compared to non-capped particles, while casein yielded only a 1.25-fold increase. In the absence of proteases, SOAP release followed first-order kinetics, resulting in sustained release over 6 days. When exposed to trypsin, the release mechanism changed from diffusion-based to anomalous non-Fickian transport with zero-order kinetics, enabling rapid and efficient SOAP release. Proteolytic degradation of the protein cap also accelerated particle degradation and aggregation, offering insights into release dynamics under physiological conditions. The BSA-capped systems (amino-SBA-15-SOAP@BSA) showed effective bacteriostatic activity against Staphylococcus aureus (S. aureus), low hemolytic activity, and high cytocompatibility toward human dermal fibroblasts, outperforming free SOAP. Additionally, BSA capping reduced nonspecific protein binding in serum-rich media. By integrating sustained SOAP delivery with protease-triggered release, the amino-SBA-15-SOAP@BSA system addresses key limitations in AMP delivery, providing a promising strategy for controlled and localized AMP delivery in the treatment of topical bacterial infections.

Introduction: Proper packing technique is crucial to minimize blood loss and successfully stop fatal junctional (axilla, groin, and neck) bleedings. Several medical simulators and mannequins are used to teach techniques for manual pressure and wound packing. Live tissue training (LTT) using animal models represents a high-fidelity simulator, but the number of times massive hemorrhage can be practiced is limited due to cumulative blood loss of the animal. Moreover, the animal’s potent coagulation limits the reuse of injuries. The study aimed at creating and validating a reproducible and repeatable exsanguination simulator to be used for high-volume training. Method: This study was approved by the regional animal ethics committee (Dnr 17953-2020). All animals were fully anesthetized throughout the duration of experiments. A repeatable exsanguination simulator using live tissue (RESULT) was created using commonly available materials to add reproducible junctional bleedings in an LTT context. A canister of porcine or bovine blood is connected to a standard gravity infusion set with roll clamp and pump chamber removed and added to a 100 cm 3-way stopcock connected to a 60 ml syringe. The free end of tubing is surgically inserted into the hind leg of a pig and placed inside a 5 cm long and 5 cm deep wound cavity. The simulator was evaluated with instructors controlling the rate of bleeding using the syringe while training participants packed the wound. Results: According to the instructors, participants benefited from the additional training made possible by using RESULT. Instructors received direct feedback on applied manual pressure and packing through the resistance of the syringe plunger. Moreover, participants found the increased number of repetitions beneficial to their training. The animals had no change in status from the multiple bleeding interventions. Conclusion: Both participants and instructors found the novel bleeding model useful for high-volume training in stopping massive junctional bleeding.

Introduction: Removal of necrotic tissue is a vital step in the treatment of full-thickness burn wounds, with surgical debridement being the most effective method. Since minor burn wounds are typically treated on an outpatient basis where surgical capabilities can be limited there is a need for alternative treatment options. In this study we aim to evaluate the use of amino acid buffered hypochlorite (AABH) as a chemical enhancement for wound debridement in a porcine infected burn wound model.Method: A total of 60 full-thickness burn wounds, 3 cm in diameter, were created on four pigs using a standardized burn device. The wounds were inoculated with 107 colonyforming units (CFU) of S. aureus. The experimental groups included wounds debrided with a plastic curette, wounds debrided after pretreatment with AABH, and control wounds wiped with gauze. Wounds were treated twice per week for three weeks. Debridement, healing, and infection parameters were evaluated over time.Results: After one week, but not after two and three weeks, the curette and AABH groups had higher debrided weights compared to control (p < 0.05). Percentage of wound area adequately cleared from necrotic tissue was higher in the AABH-group compared to the curette-group and control, after one week. The earliest healing was measured in the AABH group after two weeks (5 % of wounds), which also had the most healed wounds after three weeks (55 %). In both the AABH and the curette groups, bacterial load had fallen below 10(5) CFU/g after two weeks. No CFU were detectable in the AABH group after three weeks. The AABH-group was also the easiest to debride.Conclusion: Our results indicate that AABH facilitates wound debridement and could be a helpful addition to an effective treatment modality for removal of necrotic tissue in full thickness burns.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials.

Hydrogels of cellulose nanofibrils (CNFs) are promising wound dressing candidates due to their biocompatibility, high water absorption, and transparency. Herein, two different commercially available wood species, softwood and hardwood, were subjected to TEMPO-mediated oxidation to proceed with delignification and oxidation in a one-pot process, and thereafter, nanofibrils were isolated using a high-pressure microfluidizer. Furthermore, transparent nanofibril hydrogel networks were prepared by vacuum filtration. Nanofibril properties and network performance correlated with oxidation were investigated and compared with commercially available TEMPO-oxidized pulp nanofibrils and their networks. Softwood nanofibril hydrogel networks exhibited the best mechanical properties, and in vitro toxicological risk assessment showed no detrimental effect for any of the studied hydrogels on human fibroblast or keratinocyte cells. This study demonstrates a straightforward processing route for direct oxidation of different wood species to obtain nanofibril hydrogels for potential use as wound dressings, with softwood having the most potential.

The self-assembly of nanocellulose in the form of cellulose nanofibers (CNFs) can be accomplished via hydrogen-bonding assistance into completely bio-based hydrogels. This study aimed to use the intrinsic properties of CNFs, such as their ability to form strong networks and high absorption capacity and exploit them in the sustainable development of effective wound dressing materials. First, TEMPO-oxidized CNFs were separated directly from wood (W-CNFs) and compared with CNFs separated from wood pulp (P-CNFs). Second, two approaches were evaluated for hydrogel self-assembly from W-CNFs, where water was removed from the suspensions via evaporation through suspension casting (SC) or vacuum-assisted filtration (VF). Third, the W-CNF-VF hydrogel was compared to commercial bacterial cellulose (BC). The study demonstrates that the self-assembly via VF of nanocellulose hydrogels from wood was the most promising material as wound dressing and displayed comparable properties to that of BC and strength to that of soft tissue.

Cutaneous wounds can lead to huge suffering for patients. Early fetal wounds have the capacity to regenerate without scar formation. Amniotic fluid (AF), containing hyaluronic acid (HA), may contribute to this regenerative environment. We aimed to analyse changes in gene expression when human keratinocytes are exposed to AF or HA. Human keratinocytes were cultured to subconfluence, starved for 12 h and then randomised to be maintained in (1) Dulbecco's modified Eagle's medium (DMEM), (2) DMEM with 50% AF, or (3) DMEM with 50% fetal calf serum (FCS). Transcriptional changes were analysed using microarray and enriched with WebGestalt and Enrichr. Additionally, eight diagnostic genes were analysed using semiquantitative real‐time PCR to investigate epidermal differentiation and cellular stress after HA exposure as an alternative for AF exposure. The AF and FCS treatments resulted in enrichment of genes relating to varied aspects of epidermal and keratinocyte biology. In particular, p63‐, AP1‐ and NFE2L2‐ (Nrf2) associated genes were found significantly regulated in both treatments. More genes regulated by FCS treatment were associated with inflammatory signalling, whilst AF treatment was dominantly associated with molecular establishment of epidermis and lipid metabolic activity. HA exposure mostly resulted in gene regulation that was congruent with the AF microarray group, with increased expression of ITGA6 and LOR. We conclude that AF exposure enhances keratinocyte differentiation in vitro, which suggests that AF constituents can be beneficial for wound‐healing applications.

Background: In armed conflicts, infected wounds constitute a large portion of the surgical workload. Treatment consists of debridements, change of dressings, and antibiotics. Many surgeons advocate for the use of honey as an adjunct with the rationale that honey has bactericidal and hyperosmotic properties. However, according to a Cochrane review from 2015 there is insufficient data to draw any conclusions regarding the efficacy of honey in treatment of wounds. We, therefore, decided to evaluate if honey is non-inferior to gentamicin in the treatment of infected wounds in a highly translatable porcine wound model. Material and methods: 50 standardized wounds on two pigs were infected with S. aureus and separately treated with either topically applied Manuka honey or intramuscular gentamicin for eight days. Treatment efficacy was evaluated with quantitative cultures, wound area measurements, histological, immunohistochemical assays, and inflammatory response. Results: Topically applied Manuka honey did not reduce bacterial count or wound area for the duration of treatment. Intramuscular gentamicin initially reduced bacterial count (geometric mean 5.59*,0.37 - 4.27 *,0.80 log10 (GSD) CFU/g), but this was not sustained for the duration of the treatment. However, wound area was significantly reduced with intramuscular gentamicin at the end of treatment (mean 112.8 +/- 30.0-67.7 +/- 13.2 (SD) mm(2)). ANOVA-analysis demonstrated no variation in bacterial count for the two treatments but significant variation in wound area (p = 0.0001). The inflammatory response was more persistent in the pig with wounds treated with topically applied Manuka honey than in the pig treated with intramuscular gentamicin. Conclusion: At the end of treatment S. aureus count was the same with topically applied Manuka honey and intramuscular gentamicin. The wound area was unchanged with topically applied Manuka honey and decreased with intramuscular gentamicin. Topically applied Manuka honey could consequently be non inferior to intramuscular gentamicin in reducing S. aureus colonization on the wound's surface, but not in reducing wound size. The use of Manuka honey dressings to prevent further progression of a wound infection may therefore be of value in armed conflicts, where definite care is not immediately available. (C) 2021 The Author(s). Published by Elsevier Ltd.