Keratin Biomaterials in Skin Wound Healing, an Old Player in Modern Medicine: A Mini Review

Impaired wound healing is a major medical problem. To solve it, researchers around the world have turned their attention to the use of tissue-engineered products to aid in skin regeneration in case of acute and chronic wounds. One of the primary goals of tissue engineering and regenerative medicine is to develop a matrix or scaffold system that mimics the structure and function of native tissue. Keratin biomaterials derived from wool, hair, and bristle have been the subjects of active research in the context of tissue regeneration for over a decade. Keratin derivatives, which can be either soluble or insoluble, are utilized as wound dressings since keratins are dynamically up-regulated and needed in skin wound healing. Tissue biocompatibility, biodegradability, mechanical durability, and natural abundance are only a few of the keratin biomaterials’ properties, making them excellent wound dressing materials to treat acute and chronic wounds. Several experimental and pre-clinical studies described the beneficial effects of the keratin-based wound dressing in faster wound healing. This review focuses exclusively on the biomedical application of a different type of keratin biomaterials as a wound dressing in pre-clinical and clinical conditions.

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Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽

10.3390/molecules26092554 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2554

Author(s):

Marek Konop ◽

Anna K. Laskowska ◽

Mateusz Rybka ◽

Ewa Kłodzińska ◽

Dorota Sulejczak ◽

...

Keyword(s):

Wound Healing ◽

Wound Dressing ◽

Healing Process ◽

Skin Wound ◽

Wound Healing Process ◽

Diabetic Mice ◽

Full Thickness ◽

Skin Wound Healing ◽

Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

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The Role of Extracellular Matrix in Skin Wound Healing

Journal of Clinical Medicine ◽

10.3390/jcm10245947 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5947

Author(s):

Nikolai N. Potekaev ◽

Olga B. Borzykh ◽

German V. Medvedev ◽

Denis V. Pushkin ◽

Marina M. Petrova ◽

...

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Modern Medicine ◽

Skin Wound ◽

Economic Losses ◽

Skin Wound Healing ◽

Impaired Wound Healing ◽

Risk Levels ◽

Fundamental Research ◽

Chronic Skin

Impaired wound healing is one of the unsolved problems of modern medicine, affecting patients’ quality of life and causing serious economic losses. Impaired wound healing can manifest itself in the form of chronic skin wounds or hypertrophic scars. Research on the biology and physiology of skin wound healing disorders is actively continuing, but, unfortunately, a single understanding has not been developed. The attention of clinicians to the biological and physiological aspects of wound healing in the skin is necessary for the search for new and effective methods of prevention and treatment of its consequences. In addition, it is important to update knowledge about genetic and non-genetic factors predisposing to impaired wound healing in order to identify risk levels and develop personalized strategies for managing such patients. Wound healing is a very complex process involving several overlapping stages and involving many factors. This thematic review focuses on the extracellular matrix of the skin, in particular its role in wound healing. The authors analyzed the results of fundamental research in recent years, finding promising potential for their transition into real clinical practice.

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Hydrogel Preparation Methods and Biomaterials for Wound Dressing

Life ◽

10.3390/life11101016 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1016

Author(s):

Jingjing Su ◽

Jiankang Li ◽

Jiaheng Liang ◽

Kun Zhang ◽

Jingan Li

Keyword(s):

Wound Dressing ◽

Wound Repair ◽

Chronic Wounds ◽

Healing Process ◽

3D Structure ◽

Skin Wound ◽

Wound Dressings ◽

Wound Healing Process ◽

Skin Wound Healing ◽

Preparation Methods

Wounds have become one of the causes of death worldwide. The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds that bring great pain to patients, and there is currently no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal dressing candidate because of its 3D structure, good permeability, excellent biocompatibility, and ability to provide a moist environment for wound repair, which overcomes the shortcomings of traditional dressings. This article first briefly introduces the skin wound healing process, then the preparation methods of hydrogel dressings and the characteristics of hydrogel wound dressings made of natural biomaterials and synthetic materials are introduced. Finally, the development prospects and challenges of hydrogel wound dressings are discussed.

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The role of miRNAs in the inflammatory phase of skin wound healing

AIMS Allergy and Immunology ◽

10.3934/allergy.2021020 ◽

2021 ◽

Vol 5 (4) ◽

pp. 264-278

Author(s):

Federica Serra ◽

◽

Lisa Aielli ◽

Erica Costantini ◽

◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Chronic Wounds ◽

Medical Problem ◽

Skin Wound ◽

Skin Wound Healing ◽

Damage Site ◽

Inflammatory Phase ◽

Peripheral Cells

<abstract> <p>Wound healing (WH) is a fundamental physiological process to keep the integrity of the skin, therefore impaired and chronic WH is a common and severe medical problem and represent one of the biggest challenges of public health. The resolution of the WH inflammatory phase is characterized by a complex series of events that involves many cellular types, especially neutrophils, macrophages and inflammatory mediators, which are crucial for a correct wound closure. MicroRNAs (miRNAs) play essential roles in wound repair. In fact, miR-142 is linked to inflammation modulating neutrophils' chemotaxis and polarization, while the polarization of M1 toward the M2 phenotype is driven by miR-223 and miR-132 is linked to chemokines and cytokines that activate endothelial cells and attract leukocytes and peripheral cells to the damage site. Thus, understanding the dysregulation of miRNAs in WH will be decisive for the development of new and more effective therapies for the management of chronic wounds.</p> </abstract>

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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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The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽

10.3390/nano11020457 ◽

2021 ◽

Vol 11 (2) ◽

pp. 457

Author(s):

Andreu Blanquer ◽

Jana Musilkova ◽

Elena Filova ◽

Johanka Taborska ◽

Eduard Brynda ◽

...

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Chronic Wounds ◽

Human Keratinocytes ◽

Skin Wound ◽

Platelet Lysate ◽

Therapeutic Approaches ◽

Skin Wound Healing ◽

New Therapeutic Approaches ◽

Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020190001e1498 ◽

2020 ◽

Vol 33 (1) ◽

Author(s):

Letícia Fuganti CAMPOS ◽

Eliane TAGLIARI ◽

Thais Andrade Costa CASAGRANDE ◽

Lúcia de NORONHA ◽

Antônio Carlos L. CAMPOS ◽

...

Keyword(s):

Diabetes Mellitus ◽

Wound Healing ◽

Type I Collagen ◽

Chronic Wounds ◽

Skin Wound ◽

Diabetic Rats ◽

Control Group ◽

Type I ◽

Collagen Deposition ◽

Skin Wound Healing

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

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Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Burns & Trauma ◽

10.1093/burnst/tkaa028 ◽

2020 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Pengcheng Xu ◽

Yaguang Wu ◽

Lina Zhou ◽

Zengjun Yang ◽

Xiaorong Zhang ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Wound Repair ◽

Chronic Wounds ◽

Platelet Rich Plasma ◽

Skin Wound ◽

Local Inflammation ◽

Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

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Resveratrol-loaded peptide-hydrogels inhibit scar formation in wound healing through suppressing inflammation

Regenerative Biomaterials ◽

10.1093/rb/rbz041 ◽

2019 ◽

Cited By ~ 2

Author(s):

Chen-Chen Zhao ◽

Lian Zhu ◽

Zheng Wu ◽

Rui Yang ◽

Na Xu ◽

...

Keyword(s):

Wound Healing ◽

Damage Model ◽

Skin Wound ◽

Scar Formation ◽

Wound Dressings ◽

Skin Damage ◽

Skin Wound Healing ◽

Accelerate Wound Healing ◽

Peptide Hydrogels

Abstract Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason. The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix, hydration environment and serving as drug delivery systems. In our study, resveratrol, a polyphenol compound with anti-inflammatory effect, is loaded into peptide-hydrogel (Fmoc-FFGGRGD) to form a wound dressing (Pep/RES). Resveratrol is slowly released from the hydrogel in situ, and the release amount is controlled by the loading amount. The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages. The Pep/RES hydrogels are used as wound dressings in rat skin damage model. The results suggest that the Pep/RES dressing can accelerate wound healing rate, exhibit well-organized collagen deposition, reduce inflammation and eventually prevent scar formation. The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.

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