Efficiency of Enzymatic Debridement in the Healing Process of Chronic Wounds in Small Animal Practice

Abstract Skin wounds are a common presentation in small animal practice. These wounds may be acute or chronic with a complicated healing process. An important aspect of the healing of wounds is debridement which may be carried out by surgical, autolytic, mechanical or enzymatic methods. The debridement method is chosen according to the individual skin defect and influenced by factors such as wound size and location, the age of the wound, and the presence of infection or exudate. Enzymatic debridement is a method that is not commonly used in veterinary practice, and involves the use of enzyme preparations to remove necrotic tissue from a wound. The aim of this study was to investigate the effects of the enzymatic ointment collagenase as a method of debridement, and its effect on the macroscopic appearance of chronic skin wounds in cats and dogs. We observed that the application of Iruxol Mono directly to the wound changes the progress of the healing process, with no obvious adverse effects. The time of healing of chronic wounds was decreased and healthy granulation tissue was developed within a couple of days after application of the ointment. Enzymatic debridement appears to be a promising method of debridement for use in chronic wounds, and should be considered in cases where more conventional methods of debridement are ineffective or unsuitable.

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Systematic Review: Adipose-Derived Mesenchymal Stem Cells, Platelet-Rich Plasma and Biomaterials as New Regenerative Strategies in Chronic Skin Wounds and Soft Tissue Defects

International Journal of Molecular Sciences ◽

10.3390/ijms22041538 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1538 ◽

Cited By ~ 2

Author(s):

Pietro Gentile ◽

Simone Garcovich

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Wound Healing ◽

Soft Tissue ◽

Chronic Wounds ◽

Platelet Rich Plasma ◽

Skin Wounds ◽

Soft Tissue Defects ◽

Chronic Skin ◽

Tissue Defects

The number of clinical trials evaluating adipose-derived mesenchymal stem cells (AD-MSCs), platelet-rich plasma (PRP), and biomaterials efficacy in regenerative plastic surgery has exponentially increased during the last ten years. AD-MSCs are easily accessible from various fat depots and show intrinsic plasticity in giving rise to cell types involved in wound healing and angiogenesis. AD-MSCs have been used in the treatment of soft tissue defects and chronic wounds, employed in conjunction with a fat grafting technique or with dermal substitute scaffolds and platelet-rich plasma. In this systematic review, an overview of the current knowledge on this topic has been provided, based on existing studies and the authors’ experience. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, PRP, and biomaterials used in soft tissue defects and chronic wounds. Of the 2136 articles initially identified, 422 articles focusing on regenerative strategies in wound healing were selected and, consequently, only 278 articles apparently related to AD-MSC, PRP, and biomaterials were initially assessed for eligibility. Of these, 85 articles were excluded as pre-clinical, experimental, and in vitro studies. For the above-mentioned reasons, 193 articles were selected; of this amount, 121 letters, expert opinions, commentary, and editorials were removed. The remaining 72 articles, strictly regarding the use of AD-MSCs, PRP, and biomaterials in chronic skin wounds and soft tissue defects, were analyzed. The studies included had to match predetermined criteria according to the patients, intervention, comparator, outcomes, and study design (PICOS) approach. The information analyzed highlights the safety and efficacy of AD-MSCs, PRP, and biomaterials on soft tissue defects and chronic wounds, without major side effects.

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Hydrogel-Based Strategies to Advance Therapies for Chronic Skin Wounds

Annual Review of Biomedical Engineering ◽

10.1146/annurev-bioeng-060418-052422 ◽

2019 ◽

Vol 21 (1) ◽

pp. 145-169 ◽

Cited By ~ 19

Author(s):

Lucília P. da Silva ◽

Rui L. Reis ◽

Vitor M. Correlo ◽

Alexandra P. Marques

Keyword(s):

Tissue Engineering ◽

Chronic Wounds ◽

Significant Risk ◽

Skin Regeneration ◽

Wound Management ◽

Skin Wounds ◽

Preclinical Models ◽

Moist Environment ◽

Chronic Skin ◽

Bioactive Agents

Chronic skin wounds are the leading cause of nontraumatic foot amputations worldwide and present a significant risk of morbidity and mortality due to the lack of efficient therapies. The intrinsic characteristics of hydrogels allow them to benefit cutaneous healing essentially by supporting a moist environment. This property has long been explored in wound management to aid in autolytic debridement. However, chronic wounds require additional therapeutic features that can be provided by a combination of hydrogels with biochemical mediators or cells, promoting faster and better healing. We survey hydrogel-based approaches with potential to improve the healing of chronic wounds by reviewing their effects as observed in preclinical models. Topics covered include strategies to ablate infection and resolve inflammation, the delivery of bioactive agents to accelerate healing, and tissue engineering approaches for skin regeneration. The article concludes by considering the relevance of treating chronic skin wounds using hydrogel-based strategies.

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Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.773866 ◽

2021 ◽

Vol 8 ◽

Author(s):

Denis C. Szondi ◽

Jason K. Wong ◽

Leah A. Vardy ◽

Sheena M. Cruickshank

Keyword(s):

Chronic Wounds ◽

Chronic Wound ◽

Urea Cycle ◽

Inflammatory Responses ◽

Healing Process ◽

Cell Types ◽

Intersection Point ◽

Multiple Cell ◽

Chronic Skin ◽

Skin Conditions

Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production. The ARG pathways help balance pro- and anti-inflammatory responses in the context of wound healing. However, local and systemic dysfunctionalities of the ARG pathways have been shown to contribute to the hindrance of the healing process and the occurrence of chronic wounds. This review discusses the functions of ARG in macrophages and fibroblasts while detailing the deleterious implications of a malfunctioning ARG enzyme in chronic skin conditions such as leg ulcers. The review also highlights how ARG links with the microbiota and how this impacts on infected chronic wounds. Lastly, the review depicts chronic wound treatments targeting the ARG pathway, alongside future diagnosis and treatment perspectives.

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Interleukin-17: Potential Target for Chronic Wounds

Mediators of Inflammation ◽

10.1155/2019/1297675 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Yasmin Hadian ◽

Michelle D. Bagood ◽

Sara E. Dahle ◽

Apra Sood ◽

R. Rivkah Isseroff

Keyword(s):

Wound Healing ◽

Clinical Studies ◽

Tissue Repair ◽

Chronic Wounds ◽

Family Members ◽

Interleukin 17 ◽

Skin Wounds ◽

Interleukin 17A ◽

Chronic Skin ◽

Skin Conditions

Chronic wounds exhibit persistent inflammation with markedly delayed healing. The significant burden of chronic wounds, which are often resistant to standard therapy, prompts further research on novel therapies. Since the interleukin-17 family has been implicated as a group of proinflammatory cytokines in immune-mediated diseases in the gut and connective tissue, as well as inflammatory skin conditions, we consider here if it may contribute to the pathogenesis of chronic wounds. In this review, we discuss the interleukin-17 family’s signaling pathways and role in tissue repair. A PubMed review of the English literature on interleukin-17, wound healing, chronic wounds, and inflammatory skin conditions was conducted. Interleukin-17 family signaling is reviewed in the context of tissue repair, and preclinical and clinical studies examining its role in the skin and other organ systems are critically reviewed. The published work supports a pathologic role for interleukin-17 family members in chronic wounds, though this needs to be more conclusively proven. Clinical studies using monoclonal interleukin-17 antibodies to improve healing of chronic skin wounds have not yet been performed, and only a few studies have examined interleukin-17 family expression in chronic skin wounds. Furthermore, different interleukin-17 family members could be playing selective roles in the repair process. These studies suggest a therapeutic role for targeting interleukin-17A to promote wound healing; therefore, interleukin-17A may be a target worthy of pursuing in the near future.

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Advances in Gelatin-based Hydrogels for Wound Management

Journal of Materials Chemistry B ◽

10.1039/d0tb02582h ◽

2021 ◽

Author(s):

Jeon Il Kang ◽

Kyung Min Park

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Healing Process ◽

Wound Management ◽

Wound Healing Process ◽

Skin Wounds ◽

Normal Wound Healing

Skin wounds can be classified into two categories, namely acute and chronic. While acute wounds are healed by the normal wound healing process, chronic wounds are not normally healed, causing...

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Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds

International Journal of Molecular Sciences ◽

10.3390/ijms22083931 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3931

Author(s):

Hiromasa Tanno ◽

Emi Kanno ◽

Suzuna Sato ◽

Yu Asao ◽

Mizuki Shimono ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Wound Healing ◽

Natural Killer ◽

Chronic Wounds ◽

Bacterial Load ◽

Healing Process ◽

Skin Wounds ◽

Inkt Cells ◽

Invariant Natural Killer ◽

Natural Killer T

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.

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Effects of detergent on the sulphation of chondroitin by cell-free preparations from chick-embryo epiphyseal cartilage

Biochemical Journal ◽

10.1042/bj2850577 ◽

1992 ◽

Vol 285 (2) ◽

pp. 577-583 ◽

Cited By ~ 2

Author(s):

G Sugumaran ◽

J E Silbert

Keyword(s):

Chick Embryo ◽

Supernatant Fraction ◽

Random Pattern ◽

Type I ◽

Type Ii ◽

Enzyme Preparations ◽

Enzyme Substrate ◽

Ionic Detergent ◽

The Individual ◽

Triton X

The effects of the non-ionic detergent Triton X-100 on 6-sulphation of two species of endogenous nascent proteochondroitin by a chick-embryo cartilage microsomal system was examined. Sulphation of the larger (Type I) species with adenosine 3′-phosphate 5′-phosphosulphate was slightly diminished when Triton X-100 was present, whereas sulphation of the smaller (Type II) species was slightly enhanced. An ordered rather than random pattern of sulphation was obtained for the smaller proteoglycan, but with a considerably lower degree of sulphation than that of the larger proteochondroitin. These differences were consistent with other differences between these two species as described previously. Sulphation of exogenous [14C]chondroitin and exogenous proteo[3H]chondroitin by the microsomal system with Triton X-100 present produced ordered rather than random sulphation patterns. When a 100,000 g supernatant fraction was utilized for sulphation of [14C]chondroitin or proteo[3H]chondroitin, Triton X-100 was not needed, and ordered sulphation was still obtained. When hexasaccharide was used, sulphation of multiple N-acetylgalactosamine residues of the individual hexasaccharides resulted. This was relatively independent of Triton X-100 or the concentration of the hexasaccharide acceptors. With soluble enzyme, sulphation of multiple N-acetylgalactosamine residues on the individual hexasaccharide molecules was even greater, so that tri-sulphated products were found. This suggests that ordered rather than random sulphation of chondroitin with these enzyme preparations is due to enzyme-substrate interaction rather than to membrane organization.

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Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

Pharmaceutics ◽

10.3390/pharmaceutics13070961 ◽

2021 ◽

Vol 13 (7) ◽

pp. 961

Author(s):

Sibusiso Alven ◽

Vuyolwethu Khwaza ◽

Opeoluwa O. Oyedeji ◽

Blessing A. Aderibigbe

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Mechanical Performance ◽

Healing Process ◽

Aloe Vera ◽

Antimicrobial Properties ◽

Biological Properties ◽

Wound Management ◽

Wound Healing Process ◽

Treatment Of Wounds

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

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Identifying New Pathways and Targets for Wound Healing and Therapeutics from Natural Sources

Current Drug Delivery ◽

10.2174/1567201818666210111101257 ◽

2021 ◽

Vol 18 ◽

Author(s):

Xinchi Feng ◽

Jinsong Hao

Keyword(s):

Wound Healing ◽

Molecular Mechanisms ◽

Chronic Wounds ◽

Wound Care ◽

Healing Process ◽

Unmet Need ◽

Wound Dressings ◽

Wound Healing Process ◽

Natural Sources ◽

Viable Approach

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.

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