scholarly journals A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1622 ◽  
Author(s):  
Agata Przekora
Keyword(s):  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Topical Delivery ◽  
Artificial Skin ◽  
Skin Tissue ◽  
Wound Treatment ◽  
Skin Grafts ◽  
Skin Substitutes ◽  
Modern Approach

Chronic wounds occur as a consequence of a prolonged inflammatory phase during the healing process, which precludes skin regeneration. Typical treatment for chronic wounds includes application of autografts, allografts collected from cadaver, and topical delivery of antioxidant, anti-inflammatory, and antibacterial agents. Nevertheless, the mentioned therapies are not sufficient for extensive or deep wounds. Moreover, application of allogeneic skin grafts carries high risk of rejection and treatment failure. Advanced therapies for chronic wounds involve application of bioengineered artificial skin substitutes to overcome graft rejection as well as topical delivery of mesenchymal stem cells to reduce inflammation and accelerate the healing process. This review focuses on the concept of skin tissue engineering, which is a modern approach to chronic wound treatment. The aim of the article is to summarize common therapies for chronic wounds and recent achievements in the development of bioengineered artificial skin constructs, including analysis of biomaterials and cells widely used for skin graft production. This review also presents attempts to reconstruct nerves, pigmentation, and skin appendages (hair follicles, sweat glands) using artificial skin grafts as well as recent trends in the engineering of biomaterials, aiming to produce nanocomposite skin substitutes (nanofilled polymer composites) with controlled antibacterial activity. Finally, the article describes the composition, advantages, and limitations of both newly developed and commercially available bioengineered skin substitutes.

scholarly journals Cellular Response to Vitamin C-Enriched Chitosan/Agarose Film with Potential Application as Artificial Skin Substitute for Chronic Wound Treatment

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1185 ◽  
Author(s):  
Vladyslav Vivcharenko ◽  
Michal Wojcik ◽  
Agata Przekora
Keyword(s):  
Growth Factor ◽  
Vitamin C ◽  
Human Skin ◽  
Cellular Response ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Artificial Skin ◽  
Skin Substitute ◽  
Wound Treatment ◽  
Human Skin Fibroblasts

The treatment of chronic wounds is still a meaningful challenge to physicians. The aim of this work was to produce vitamin C-enriched chitosan/agarose (CHN/A) film that could serve as potential artificial skin substitute for chronic wound treatment. The biomaterial was fabricated by a newly developed and simplified method via mixing acidic chitosan solution with alkaline agarose solution that allowed to obtain slightly acidic pH (5.97) of the resultant material, which is known to support skin regeneration. Vitamin C was immobilized within the matrix of the film by entrapment method during production process. Produced films (CHN/A and CHN/A + vit C) were subjected to comprehensive evaluation of cellular response with the use of human skin fibroblasts, epidermal keratinocytes, and macrophages. It was demonstrated that novel biomaterials support adhesion and growth of human skin fibroblasts and keratinocytes, have ability to slightly reduce transforming growth factor-beta 1 (TGF-β1) (known to be present at augmented levels in the epidermis of chronic wounds), and increase platelet-derived growth factor-BB (PDGF-BB) secretion by the cells. Nevertheless, addition of vitamin C to the biomaterial formulation does not significantly improve its biological properties due to burst vitamin release profile. Obtained results clearly demonstrated that produced CHN/A film has great potential to be used as cellular dermal, epidermal, or dermo-epidermal graft pre-seeded with human skin cells for chronic wound treatment.

scholarly journals Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3401
Author(s):  
David Meléndez-Martínez ◽  
Luis Fernando Plenge-Tellechea ◽  
Ana Gatica-Colima ◽  
Martha Sandra Cruz-Pérez ◽  
José Manuel Aguilar-Yáñez ◽  
...  
Keyword(s):  
Wound Healing ◽  
Serine Proteases ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Wound Healing Process ◽  
Major Health Problem ◽  
Normal Wound Healing ◽  
Alternative Sources ◽  
Fibrin Clots

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

scholarly journals Antlerogenic stem cells extract accelerate chronic wound healing: a preliminary study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Janusz Kmiecik ◽  
Michał Jerzy Kulus ◽  
Jarosław Popiel ◽  
Agnieszka Cekiera ◽  
Marek Cegielski
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Wound Care ◽  
Small Population ◽  
Area Ratio ◽  
Wound Treatment ◽  
Ki 67 ◽  
Pressure Therapy

Abstract Background Chronic wounds constitute a significant medical and social problem. Chronic wound treatment may be supported by various techniques, such as negative pressure therapy, phototherapy or stem cells therapy, yet most of those supporting therapies need more evidence to be used for standard wound care. Current study covers the use of sonicated Antlerogenic Stem Cells (ASC) extract on chronic wounds. Methods Study was performed on 20 dermatological patients with venous leg ulcers, divided into two groups – treated with and without ASC extract respectively. The area and circumference of the wounds during the follow-up visits were measured on the wound imprint. Dynamics of wound healing was determined and compared between control and study group; statistics includes changes in absolute values (wound area, circumference), as well as relative (percentage of wound decrease, circumference/area ratio) and their change in time. For the purpose of Ki-67 immunohistochemical staining, sections were sampled from the wound edge at distinct check-points during therapy. Results of both groups were compared with Student test or Mann-Whitney test, depending on results distribution. Results Besides Ki-67 expression, all tested wound healing parameters (including relative and absolute wound decrease and changes in circumference/area ratio) were statistically significant more favorable in experimental group. Conclusion ASC extract significantly supported standard chronic wound treatment. Due to small population of study the results should be considered preliminary, yet promising for further research.

scholarly journals Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Álvaro Sierra-Sánchez ◽  
Kevin H. Kim ◽  
Gonzalo Blasco-Morente ◽  
Salvador Arias-Santiago
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Human Cell ◽  
Chronic Wounds ◽  
Healing Process ◽  
Wound Healing Process ◽  
Future Perspectives ◽  
Skin Substitutes ◽  
Cell Potential ◽  
Engineered Skin Substitutes

AbstractWound healing is an important function of skin; however, after significant skin injury (burns) or in certain dermatological pathologies (chronic wounds), this important process can be deregulated or lost, resulting in severe complications. To avoid these, studies have focused on developing tissue-engineered skin substitutes (TESSs), which attempt to replace and regenerate the damaged skin. Autologous cultured epithelial substitutes (CESs) constituted of keratinocytes, allogeneic cultured dermal substitutes (CDSs) composed of biomaterials and fibroblasts and autologous composite skin substitutes (CSSs) comprised of biomaterials, keratinocytes and fibroblasts, have been the most studied clinical TESSs, reporting positive results for different pathological conditions. However, researchers’ purpose is to develop TESSs that resemble in a better way the human skin and its wound healing process. For this reason, they have also evaluated at preclinical level the incorporation of other human cell types such as melanocytes, Merkel and Langerhans cells, skin stem cells (SSCs), induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs). Among these, MSCs have been also reported in clinical studies with hopeful results. Future perspectives in the field of human-TESSs are focused on improving in vivo animal models, incorporating immune cells, designing specific niches inside the biomaterials to increase stem cell potential and developing three-dimensional bioprinting strategies, with the final purpose of increasing patient’s health care. In this review we summarize the use of different human cell populations for preclinical and clinical TESSs under research, remarking their strengths and limitations and discuss the future perspectives, which could be useful for wound healing purposes.

scholarly journals An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4610
Author(s):  
Hye-Jin Lee ◽  
Moses Jeong ◽  
Young-Guk Na ◽  
Sung-Jin Kim ◽  
Hong-Ki Lee ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Double Emulsion ◽  
Average Diameter ◽  
Diabetic Rats ◽  
Wound Healing Process ◽  
Nanostructured Lipid Carrier

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF–Cur-NLC). EGF–Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF–Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF–Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF–Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF–Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

scholarly journals Immunology of Acute and Chronic Wound Healing

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 700
Author(s):  
Kamila Raziyeva ◽  
Yevgeniy Kim ◽  
Zharylkasyn Zharkinbekov ◽  
Kuat Kassymbek ◽  
Shiro Jimi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Inflammatory Factors ◽  
Wound Healing Process ◽  
Macrophage Phenotype ◽  
Microbial Biofilms ◽  
Inflammatory Phase ◽  
Persistent Inflammation

Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

scholarly journals Preliminary Characterization of a Polycaprolactone-SurgihoneyRO Electrospun Mesh for Skin Tissue Engineering

Materials ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 89
Author(s):  
Enes Aslan ◽  
Cian Vyas ◽  
Joel Yupanqui Mieles ◽  
Gavin Humphreys ◽  
Carl Diver ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Healing Process ◽  
Antibacterial Properties ◽  
Dermal Fibroblasts ◽  
Wound Dressings ◽  
Skin Tissue ◽  
Loss Of Function ◽  
Skin Substitutes ◽  
Disk Diffusion Test ◽  
Skin Tissue Engineering

Skin is a hierarchical and multi-cellular organ exposed to the external environment with a key protective and regulatory role. Wounds caused by disease and trauma can lead to a loss of function, which can be debilitating and even cause death. Accelerating the natural skin healing process and minimizing the risk of infection is a clinical challenge. Electrospinning is a key technology in the development of wound dressings and skin substitutes as it enables extracellular matrix-mimicking fibrous structures and delivery of bioactive materials. Honey is a promising biomaterial for use in skin tissue engineering applications and has antimicrobial properties and potential tissue regenerative properties. This preliminary study investigates a solution electrospun composite nanofibrous mesh based on polycaprolactone and a medical grade honey, SurgihoneyRO. The processing conditions were optimized and assessed by scanning electron microscopy to fabricate meshes with uniform fiber diameters and minimal presence of beads. The chemistry of the composite meshes was examined using Fourier transform infrared spectroscopy and X-ray photon spectroscopy showing incorporation of honey into the polymer matrix. Meshes incorporating honey had lower mechanical properties due to lower polymer content but were more hydrophilic, resulting in an increase in swelling and an accelerated degradation profile. The biocompatibility of the meshes was assessed using human dermal fibroblasts and adipose-derived stem cells, which showed comparable or higher cell metabolic activity and viability for SurgihoneyRO-containing meshes compared to polycaprolactone only meshes. The meshes showed no antibacterial properties in a disk diffusion test due to a lack of hydrogen peroxide production and release. The developed polycaprolactone-honey nanofibrous meshes have potential for use in skin applications.

scholarly journals Molecular systems for targeted delivery and controlled release of growth factors for chronic wound treatment

2020 ◽  
Vol 5 (3) ◽  
pp. 6-15
Author(s):  
A. R. Lipunov ◽  
I. M. Afanasov ◽  
E. S. Vorobeva ◽  
A. B. Chuhnina ◽  
M. G. Gladkova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Controlled Release ◽  
Targeted Delivery ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Healing Process ◽  
Free Form ◽  
Signaling Proteins ◽  
Molecular Systems ◽  
Proliferation And Differentiation

Growth factors (GFs) are endogenous signaling proteins, that regulate cell migration, proliferation and differentiation in tissue regeneration. GFs’ concentrations in chronic wounds are pathologically reduced. This leads to a disruption of the healing process and makes chronic wounds treatment more complicated. There are drugs currently used in clinical practice, that contain GFs in a free form. However, their efficiency for chronic wounds treatment is limited, as GFs are quickly degraded in a proteolytic environment of chronic wounds. In order to overcome this limitation biocompatible molecular systems for targeted delivery and controlled release are proposed, such as: micro- and nanoparticles, hydrogels, scaffolds. GFs roles in the healing process, chronic wounds pathophysiology and molecular systems for GFs targeted delivery and controlled release are reviewed.

scholarly journals Honey in wound healing: An updated review

2021 ◽  
Vol 16 (1) ◽  
pp. 1091-1100
Author(s):  
Hanaa Tashkandi
Keyword(s):  
Wound Healing ◽  
Antimicrobial Agents ◽  
Chronic Wounds ◽  
Healing Process ◽  
Trauma Surgery ◽  
Resistant Bacteria ◽  
Multiple Drug ◽  
Wound Healing Process ◽  
Wound Treatment ◽  
Application Procedure

Abstract Wound healing is a complex process with many interdependent pathophysiological and immunological mediators to restore the cellular integrity of damaged tissue. Cutaneous wound healing is the repair response to a multitude of pathologies induced by trauma, surgery, and burn leading to the restoration and functionality of the compromised cells. Many different methods have been employed to treat acute and chronic wounds, such as antimicrobial therapy, as most wounds are susceptible to infection from microbes and are difficult to treat. However, many antimicrobial agents have become ineffective in wound treatment due to the emergence of multiple drug-resistant bacteria, and failures in current wound treatment methods have been widely reported. For this reason, alternative therapies have been sought, one of which is the use of honey as a wound treatment agent. The use of honey has recently gained clinical popularity for possible use in wound treatment and regenerative medicine. With this high demand, a better delivery and application procedure is required, as well as research aiming at its bioactivity. Honey is a safe natural substance, effective in the inhibition of bacterial growth and the treatment of a broad range of wound types, including burns, scratches, diabetic boils (Skin abscesses associated with diabetic), malignancies, leprosy, fistulas, leg ulcers, traumatic boils, cervical and varicose ulcers, amputation, burst abdominal wounds, septic and surgical wounds, cracked nipples, and wounds in the abdominal wall. Honey comprises a wide variety of active compounds, including flavonoids, phenolic acid, organic acids, enzymes, and vitamins, that may act to improve the wound healing process. Tissue-engineered scaffolds have recently attracted a great deal of attention, and various scaffold fabrication techniques are being researched. Some incorporate honey to improve their delivery during wound treatment. Hence, the aim of this review is to summarize recent studies on the wound healing properties of honey.

Conductive dual hydrogen bonding hydrogels for the electrical stimulation of infected chronic wounds

2021 ◽  
Vol 9 (38) ◽  
pp. 8138-8146
Author(s):  
Ye Wu ◽  
Yuhui Lu ◽  
Can Wu ◽  
Jiali Chen ◽  
Ning Ning ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Antimicrobial Activity ◽  
Hydrogen Bonding ◽  
Electrical Stimulation ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Great Promise ◽  
Wound Treatment ◽  
Conductive Hydrogels ◽  
Stimulation Of

Polyaniline provides skin-mimic electrical conductivity and functionalized quaternary ammonium groups show intense antimicrobial activity. Electrical stimulation using conductive hydrogels shows great promise for chronic wound treatment.

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