Modulation of macrophage functions by ECM-inspired wound dressings – a promising therapeutic approach for chronic wounds

Abstract Nonhealing chronic wounds are among the most common skin disorders with increasing incidence worldwide. However, their treatment is still dissatisfying, that is why novel therapeutic concepts targeting the sustained inflammatory process have emerged. Increasing understanding of chronic wound pathologies has put macrophages in the spotlight of such approaches. Herein, we review current concepts and perspectives of therapeutic macrophage control by ECM-inspired wound dressing materials. We provide an overview of the current understanding of macrophage diversity with particular view on their roles in skin and in physiological and disturbed wound healing processes. Based on this we discuss strategies for their modulation in chronic wounds and how such strategies can be tailored in ECM-inspired wound dressing. The latter utilize and mimic general principles of ECM-mediated cell control, such as binding and delivery of signaling molecules and direct signaling to cells specifically adapted for macrophage regulation in wounds. In this review, we present examples of most recent approaches and discuss ideas for their further development.

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Peptide-Cellulose Conjugates on Cotton-Based Materials Have Protease Sensor/Sequestrant Activity

Sensors ◽

10.3390/s18072334 ◽

2018 ◽

Vol 18 (7) ◽

pp. 2334 ◽

Cited By ~ 7

Author(s):

J. Edwards ◽

Krystal Fontenot ◽

Falk Liebner ◽

Brian Condon

Keyword(s):

Wound Dressing ◽

Chronic Wounds ◽

Chronic Wound ◽

Point Of Care ◽

Absorption Capacity ◽

Wound Dressings ◽

Human Neutrophil Elastase ◽

World Population ◽

Molecular Features ◽

Sensor Sensitivity

The growing incidence of chronic wounds in the world population has prompted increased interest in chronic wound dressings with protease-modulating activity and protease point of care sensors to treat and enable monitoring of elevated protease-based wound pathology. However, the overall design features needed for the combination of a chronic wound dressing that lowers protease activity along with protease detection capability as a single platform for semi-occlusive dressings has scarcely been addressed. The interface of dressing and sensor specific properties (porosity, permeability, moisture uptake properties, specific surface area, surface charge, and detection) relative to sensor bioactivity and protease sequestrant performance is explored here. Measurement of the material’s zeta potential demonstrated a correlation between negative charge and the ability of materials to bind positively charged Human Neutrophil Elastase. Peptide-cellulose conjugates as protease substrates prepared on a nanocellulosic aerogel were assessed for their compatibility with chronic wound dressing design. The porosity, wettability and absorption capacity of the nanocellulosic aerogel were consistent with values observed for semi-occlusive chronic wound dressing designs. The relationship of properties that effect dressing functionality and performance as well as impact sensor sensitivity are discussed in the context of the enzyme kinetics. The sensor sensitivity of the aerogel-based sensor is contrasted with current clinical studies on elastase. Taken together, comparative analysis of the influence of molecular features on the physical properties of three forms of cellulosic transducer surfaces provides a meaningful assessment of the interface compatibility of cellulose-based sensors and corresponding protease sequestrant materials for potential use in chronic wound sensor/dressing design platforms.

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Fabrication of Hybrid Nanofibers from Biopolymers and Poly (Vinyl Alcohol)/Poly (ε-Caprolactone) for Wound Dressing Applications

Polymers ◽

10.3390/polym13132104 ◽

2021 ◽

Vol 13 (13) ◽

pp. 2104

Author(s):

Sibusiso Alven ◽

Blessing Atim Aderibigbe

Keyword(s):

Mechanical Properties ◽

Wound Healing ◽

Vinyl Alcohol ◽

Wound Dressing ◽

Chronic Wounds ◽

Cellular Adhesion ◽

Wound Dressings ◽

Poly Vinyl Alcohol ◽

High Porosity ◽

Hybrid Nanofibers

The management of chronic wounds is challenging. The factors that impede wound healing include malnutrition, diseases (such as diabetes, cancer), and bacterial infection. Most of the presently utilized wound dressing materials suffer from severe limitations, including poor antibacterial and mechanical properties. Wound dressings formulated from the combination of biopolymers and synthetic polymers (i.e., poly (vinyl alcohol) or poly (ε-caprolactone) display interesting properties, including good biocompatibility, improved biodegradation, good mechanical properties and antimicrobial effects, promote tissue regeneration, etc. Formulation of these wound dressings via electrospinning technique is cost-effective, useful for uniform and continuous nanofibers with controllable pore structure, high porosity, excellent swelling capacity, good gaseous exchange, excellent cellular adhesion, and show a good capability to provide moisture and warmth environment for the accelerated wound healing process. Based on the above-mentioned outstanding properties of nanofibers and the unique properties of hybrid wound dressings prepared from poly (vinyl alcohol) and poly (ε-caprolactone), this review reports the in vitro and in vivo outcomes of the reported hybrid nanofibers.

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Nanofiber Wound Dressing Materials—A Comparative Study of Wound Healing on a Porcine Model

Military Medicine ◽

10.1093/milmed/usab155 ◽

2021 ◽

Author(s):

Katerina Menclová ◽

Petr Svoboda ◽

Jan Hadač ◽

Štefan Juhás ◽

Jana Juhásová ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Blood Count ◽

Serum Amyloid A ◽

Porcine Model ◽

Serum Amyloid ◽

Wound Dressings ◽

Amyloid A ◽

Inflammatory Phase ◽

Dressing Materials

ABSTRACT Background Nanofiber wound dressings remain the domain of in vitro studies. The purpose of our study was to verify the benefits of chitosan (CTS) and polylactide (PLA)-based nanofiber wound dressings on a porcine model of a naturally contaminated standardized wound and compare them with the conventional dressings, i.e., gauze and Inadine. Material and Methods The study group included 32 pigs randomized into four homogeneous groups according to the wound dressing type. Standardized wounds were created on their backs, and wound dressings were regularly changed. We evaluated difficulty of handling individual dressing materials and macroscopic appearance of the wounds. Wound swabs were taken for bacteriological examination. Blood samples were obtained to determine blood count values and serum levels of acute phase proteins (serum amyloid A, C-reactive protein, and haptoglobin). The crucial point of the study was histological analysis. Microscopic evaluation was focused on the defect depth and tissue reactions, including formation of the fibrin exudate with neutrophil granulocytes, the layer of granulation and cellular connective tissue, and the reepithelialization. Statistical analysis was performed by using SPSS software. The analysis was based on the Kruskal–Wallis H test and Mann–Whitney U test followed by Bonferroni correction. Significance was set at P < .05. Results Macroscopic examination did not show any difference in wound healing among the groups. However, evaluation of histological findings demonstrated that PLA-based nanofiber dressing accelerated the proliferative (P = .025) and reepithelialization (P < .001) healing phases, while chitosan-based nanofiber dressing potentiated and accelerated the inflammatory phase (P = .006). No statistically significant changes were observed in the blood count or acute inflammatory phase proteins during the trial. Different dynamics were noted in serum amyloid A values in the group treated with PLA-based nanofiber dressing (P = .006). Conclusion Based on the microscopic examination, we have documented a positive effect of nanofiber wound dressings on acceleration of individual phases of the healing process. Nanofiber wound dressings have a potential to become in future part of the common wound care practice.

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Marine Algae Polysaccharides as Basis for Wound Dressings, Drug Delivery, and Tissue Engineering: A Review

Journal of Marine Science and Engineering ◽

10.3390/jmse8070481 ◽

2020 ◽

Vol 8 (7) ◽

pp. 481 ◽

Cited By ~ 6

Author(s):

Tatyana A. Kuznetsova ◽

Boris G. Andryukov ◽

Natalia N. Besednova ◽

Tatyana S. Zaporozhets ◽

Andrey V. Kalinin

Keyword(s):

Drug Delivery ◽

Tissue Engineering ◽

Regenerative Medicine ◽

Wound Dressing ◽

Biological Properties ◽

Wound Dressings ◽

Tissue Engineering Scaffolds ◽

Treatment Of Wounds ◽

New Generation ◽

Dressing Materials

The present review considers the physicochemical and biological properties of polysaccharides (PS) from brown, red, and green algae (alginates, fucoidans, carrageenans, and ulvans) used in the latest technologies of regenerative medicine (tissue engineering, modulation of the drug delivery system, and the design of wound dressing materials). Information on various types of modern biodegradable and biocompatible PS-based wound dressings (membranes, foams, hydrogels, nanofibers, and sponges) is provided; the results of experimental and clinical trials of some dressing materials in the treatment of wounds of various origins are analyzed. Special attention is paid to the ability of PS to form hydrogels, as hydrogel dressings meet the basic requirements set out for a perfect wound dressing. The current trends in the development of new-generation PS-based materials for designing drug delivery systems and various tissue-engineering scaffolds, which makes it possible to create human-specific tissues and develop target-oriented and personalized regenerative medicine products, are also discussed.

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Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies

Polymers ◽

10.3390/polym12092168 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2168

Author(s):

Ibrahim N. Amirrah ◽

Mohd Farhanulhakim Mohd Razip Wee ◽

Yasuhiko Tabata ◽

Ruszymah Bt Hj Idrus ◽

Abid Nordin ◽

...

Keyword(s):

Wound Healing ◽

Clinical Trials ◽

Clinical Studies ◽

Wound Dressing ◽

Chronic Wounds ◽

Gentian Violet ◽

Antibacterial Properties ◽

Small Sample ◽

Wound Dressings ◽

Sample Sizes

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

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ACTIVE PRINCIPLES APPLIED ON BIOMATERIALS FOR THE CURATIVE THERAPY OF INFLAMMATORY SKIN DISEASES - A REVIEW

TEXTEH Proceedings ◽

10.35530/tt.2021.04 ◽

2021 ◽

Vol 2021 ◽

pp. 229-237

Author(s):

A. Țigău ◽

G. Vasile ◽

L. Chirilă ◽

A. Popescu ◽

S. Olaru

Keyword(s):

Drug Delivery ◽

Wound Dressing ◽

Metallic Nanoparticles ◽

Chronic Wounds ◽

Skin Diseases ◽

Trauma Surgery ◽

External Environment ◽

Wound Dressings ◽

Drug Release Profile ◽

Inflammatory Skin Diseases

Every year, millions of peoples are affected by skin injuries of either an acute or chronic nature. Worldwide 300,000 people die every year in lower-middle-income countries due to chronic wounds and burn injuries. Wounds are described as the disruption in the skin integrity and function, which arises from different causes such as trauma, surgery, diabetes, and burns. Skin provides a mechanical barrier against the external environment and has further roles in thermoregulation, metabolism and regulation of fluid balance. Skin diseases can affect each of these regions and they can be influenced by body size, sex, age, medications, diet, and microenvironment. Also, they can manifest whether the skin is healthy or diseased. Wound dressings are critical to wound care, providing a physical barrier between the wound and the external environment to prevent further damage or infection. The most promising wound dressings are biocompatible, enable physical protection of the wound milieu against penetration of bacteria and are highly porous. The use of natural biocompatible drugs is highly desirable in wound dressing compared to synthetic chemicals. To achieve an adequate therapeutic effect, different polymeric systems are used for drug delivery. To improve drug efficacy, safety, patient compliance and convenience a drug delivery system is modified to enhance drug release profile, absorption, distribution and elimination of the drug. The present review is an attempt to brief readers about the engineering of wound dressing materials from natural and synthetic sources upfront using active principles, such as bee products, drugs, essential oils, metallic nanoparticles and vitamins.

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Current Trends in Advanced Alginate-Based Wound Dressings for Chronic Wounds

Journal of Personalized Medicine ◽

10.3390/jpm11090890 ◽

2021 ◽

Vol 11 (9) ◽

pp. 890

Author(s):

Andreea Barbu ◽

Bogdan Neamtu ◽

Marius Zăhan ◽

Gabriela Mariana Iancu ◽

Ciprian Bacila ◽

...

Keyword(s):

Wound Healing ◽

Chronic Inflammation ◽

Wound Dressing ◽

Chronic Wounds ◽

Healing Process ◽

Wound Dressings ◽

In Vivo Studies ◽

Public Health Issue ◽

Wound Healing Process ◽

Special Importance

Chronic wounds represent a major public health issue, with an extremely high cost worldwide. In healthy individuals, the wound healing process takes place in different stages: inflammation, cell proliferation (fibroblasts and keratinocytes of the dermis), and finally remodeling of the extracellular matrix (equilibrium between metalloproteinases and their inhibitors). In chronic wounds, the chronic inflammation favors exudate persistence and bacterial film has a special importance in the dynamics of chronic inflammation in wounds that do not heal. Recent advances in biopolymer-based materials for wound healing highlight the performance of specific alginate forms. An ideal wound dressing should be adherent to the wound surface and not to the wound bed, it should also be non-antigenic, biocompatible, semi-permeable, biodegradable, elastic but resistant, and cost-effective. It has to give protection against bacterial, infectious, mechanical, and thermal agents, to modulate the level of wound moisture, and to entrap and deliver drugs or other molecules This paper explores the roles of alginates in advanced wound-dressing forms with a particular emphasis on hydrogels, nanofibers networks, 3D-scaffolds or sponges entrapping fibroblasts, keratinocytes, or drugs to be released on the wound-bed. The latest research reports are presented and supported with in vitro and in vivo studies from the current literature.

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Healing Effect of Vicenin-2 (VCN-2) on Human Dermal Fibroblast (HDF) and Development VCN-2 Hydrocolloid Film Based on Alginate as Potential Wound Dressing

BioMed Research International ◽

10.1155/2020/4730858 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Woan Sean Tan ◽

Palanisamy Arulselvan ◽

Shiow-Fern Ng ◽

Che Norma Mat Taib ◽

Murni Nazira Sarian ◽

...

Keyword(s):

Wound Healing ◽

Drug Release ◽

Wound Dressing ◽

Wound Repair ◽

Chronic Wounds ◽

Dermal Fibroblast ◽

Wound Dressings ◽

Dependent Manner ◽

Synthetic Compound ◽

Study Results

Chronic wounds represent serious globally health care and economic issues especially for patients with hyperglycemic condition. Wound dressings have a predominant function in wound treatment; however, the dressings for the long-lasting and non-healing wounds are still a significant challenge in the wound care management market. Astonishingly, advanced wound dressing which is embedded with a synthetic drug compound in a natural polymer compound that acts as drug release carrier has brought about promising treatment effect toward injured wound. In the current study, results have shown that Vicenin-2 (VCN-2) compound in low concentration significantly enhanced cell proliferation and migration of HDF. It also regulated the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α from HDF in wound repair. Treatment of VCN-2 also has facilitated the expression of TGF-1β and VEGF wound healing maker in a dose-dependent manner. A hydrocolloid film based on sodium alginate (SA) incorporated with VCN-2 synthetic compound which targets to promote wound healing particularly in diabetic condition was successfully developed and optimized for its physico-chemical properties. It was discovered that all the fabricated film formulations prepared were smooth, translucent, and good with flexibility. The thickness and weight of the formulations were also found to be uniform. The hydrophilic polymer comprised of VCN-2 were shown to possess desirable wound dressing properties and superior mechanical characteristics. The drug release profiles have revealed hydrocolloid film, which is able to control and sustain the VCN-2 released to wound area. In short, hydrocolloid films consisting of VCN-2 formulations are suitably used as a potential wound dressing to promote restoration of wound injury.

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Electrospun Gelatin Fibers Surface Loaded ZnO Particles as a Potential Biodegradable Antibacterial Wound Dressing

Nanomaterials ◽

10.3390/nano9040525 ◽

2019 ◽

Vol 9 (4) ◽

pp. 525 ◽

Cited By ~ 9

Author(s):

Yu Chen ◽

Weipeng Lu ◽

Yanchuan Guo ◽

Yi Zhu ◽

Yeping Song

Keyword(s):

Antibacterial Activity ◽

Wound Dressing ◽

Wound Dressings ◽

X Ray ◽

E Coli ◽

Particle Size Analyzer ◽

Zno Particles ◽

Electrospun Gelatin ◽

Dressing Materials ◽

Application Prospects

Traditional wound dressings require frequent replacement, are prone to bacterial growth and cause a lot of environmental pollution. Therefore, biodegradable and antibacterial dressings are eagerly desired. In this paper, gelatin/ZnO fibers were first prepared by side-by-side electrospinning for potential wound dressing materials. The morphology, composition, cytotoxicity and antibacterial activity were characterized by using Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), particle size analyzer (DLS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), thermogravimetry (TGA) and Incucyte™ Zoom system. The results show that ZnO particles are uniformly dispersed on the surface of gelatin fibers and have no cytotoxicity. In addition, the gelatin/ZnO fibers exhibit excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with a significant reduction of bacteria to more than 90%. Therefore, such a biodegradable, nontoxic and antibacterial fiber has excellent application prospects in wound dressing.

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In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator

Polymers ◽

10.3390/polym13020249 ◽

2021 ◽

Vol 13 (2) ◽

pp. 249

Author(s):

Anna Blasi-Romero ◽

Carlos Palo-Nieto ◽

Corine Sandström ◽

Jonas Lindh ◽

Maria Strømme ◽

...

Keyword(s):

Protease Activity ◽

Chronic Wounds ◽

Chronic Wound ◽

Cellulose Nanofibrils ◽

Dermal Fibroblasts ◽

Wound Dressings ◽

Thiol Groups ◽

The Stability ◽

Over Time

There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1–0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.

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