Epigallocatechin Gallate: The Emerging Wound Healing Potential of Multifunctional Biomaterials for Future Precision Medicine Treatment Strategies

Immediate treatment for cutaneous injuries is a realistic approach to improve the healing rate and minimise the risk of complications. Multifunctional biomaterials have been proven to be a potential strategy for chronic skin wound management, especially for future advancements in precision medicine. Hence, antioxidant incorporated biomaterials play a vital role in the new era of tissue engineering. A bibliographic investigation was conducted on articles focusing on in vitro, in vivo, and clinical studies that evaluate the effect and the antioxidants mechanism exerted by epigallocatechin gallate (EGCG) in wound healing and its ability to act as reactive oxygen species (ROS) scavengers. Over the years, EGCG has been proven to be a potent antioxidant efficient for wound healing purposes. Therefore, several novel studies were included in this article to shed light on EGCG incorporated biomaterials over five years of research. However, the related papers under this review’s scope are limited in number. All the studies showed that biomaterials with scavenging ability have a great potential to combat chronic wounds and assist the wound healing process against oxidative damage. However, the promising concept has faced challenges extending beyond the trial phase, whereby the implementation of these biomaterials, when exposed to an oxidative stress environment, may disrupt cell proliferation and tissue regeneration after transplantation. Therefore, thorough research should be executed to ensure a successful therapy.

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Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

International Journal of Molecular Sciences ◽

10.3390/ijms22084087 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4087

Author(s):

Maria Quitério ◽

Sandra Simões ◽

Andreia Ascenso ◽

Manuela Carvalheiro ◽

Ana Paula Leandro ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

In Vitro Release ◽

Peptide Hormone ◽

Plga Nanoparticles ◽

Wound Healing Process ◽

Target Area ◽

Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

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In Vivo Testing of Sericin-Polyurethane Nanofiber Mats for Wound Healing in Rats

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.751.581 ◽

2017 ◽

Vol 751 ◽

pp. 581-585 ◽

Cited By ~ 1

Author(s):

Piyaporn Kampeerapappun ◽

Pornpen Siridamrong

Keyword(s):

Wound Healing ◽

Healing Process ◽

Active Agent ◽

L929 Cell ◽

Wound Healing Process ◽

Original Size ◽

Nanofiber Mats ◽

Dressing Materials

The objective of this study was to investigate sericin-polyurethane nanofiber cover (SUC) for wound dressing materials in a rat skin. Sericin-polyurethane blended nanofibers were fabricated by using electrospinning. The composition of 3%w/v polyurethane in ethanol and 19% w/v sericin were blended and electrospun at 15 kV, 20 cm from tip to collector with a feed rate of 6.2 ml/hr. The mats, approximately 1.5 mm thick, were sterile by gamma irradiation with a radiation dose of 15 kGy. The samples of in vitro and in vivo testing were separated into three groups; gauze, polyurethane nanofiber cover (UC), and SUC. In vitro cultured L929 cell lines were investigated with inverted microscope. It was found that cells migrated to SCU. For in vivo tests, the remaining wound in rats was measured on day 2-14 after excision. Compared to original size of wound samples, the size of the wound remained 24% for SUC, 33% for gauze, and 34% for UC at day 8. The sericin, an active agent, contained in SUC mats was about 5 µl at 1.5 ×1.5 cm. It can be concluded that sericin is non-toxic to cells and can promote wound healing process in rats.

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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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The Efficacy of Silver-Based Electrospun Antimicrobial Dressing in Accelerating the Regeneration of Partial Thickness Burn Wounds Using a Porcine Model

Polymers ◽

10.3390/polym13183116 ◽

2021 ◽

Vol 13 (18) ◽

pp. 3116

Author(s):

Thien Do ◽

Tien Nguyen ◽

Minh Ho ◽

Nghi Nguyen ◽

Thai Do ◽

...

Keyword(s):

Wound Healing ◽

Burn Injury ◽

Healing Process ◽

Bactericidal Effect ◽

Wound Healing Process ◽

Burn Wounds ◽

Partial Thickness Burn ◽

Tissue Damages

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel® Ag and UrgoTulTM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.

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Systemic and topical administration of spermidine accelerates skin wound healing

10.21203/rs.3.rs-111107/v1 ◽

2020 ◽

Author(s):

Daisuke Ito ◽

Hiroyasu Ito ◽

Takayasu Ideta ◽

Ayumu Kanbe ◽

Soranobu Ninomiya ◽

...

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Wound Repair ◽

Healing Process ◽

Topical Administration ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

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The Wound Healing Potential of Aspilia africana (Pers.) C. D. Adams (Asteraceae)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/7957860 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Richard Komakech ◽

Motlalepula Gilbert Matsabisa ◽

Youngmin Kang

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Antioxidant Activities ◽

Healing Process ◽

Flowering Plant ◽

Wound Healing Process ◽

Integral Role ◽

Low Toxicity

Wounds remain one of the major causes of death worldwide. Over the years medicinal plants and natural compounds have played an integral role in wound treatment. Aspilia africana (Pers.) C. D. Adams which is classified among substances with low toxicity has been used for generations in African traditional medicine to treat wounds, including stopping bleeding even from severed arteries. This review examined the potential of the extracts and phytochemicals from A. africana, a common herbaceous flowering plant which is native to Africa in wound healing. In vitro and in vivo studies have provided strong pharmacological evidences for wound healing effects of A. africana-derived extracts and phytochemicals. Singly or in synergy, the different bioactive phytochemicals including alkaloids, saponins, tannins, flavonoids, phenols, terpenoids, β-caryophyllene, germacrene D, α-pinene, carene, phytol, and linolenic acid in A. africana have been observed to exhibit a very strong anti-inflammatory, antimicrobial, and antioxidant activities which are important processes in wound healing. Indeed, A. africana wound healing ability is furthermore due to the fact that it can effectively reduce wound bleeding, hasten wound contraction, increase the concentration of basic fibroblast growth factor (BFGF) and platelet derived growth factor, and stimulate the haematological parameters, including white and red blood cells, all of which are vital components for the wound healing process. Therefore, these facts may justify why A. africana is used to treat wounds in ethnomedicine.

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Gelatin-Based Hybrid Scaffolds: Promising Wound Dressings

Polymers ◽

10.3390/polym13172959 ◽

2021 ◽

Vol 13 (17) ◽

pp. 2959 ◽

Cited By ~ 2

Author(s):

Sindi P. Ndlovu ◽

Kwanele Ngece ◽

Sibusiso Alven ◽

Blessing A. Aderibigbe

Keyword(s):

Mechanical Properties ◽

Antimicrobial Activity ◽

Wound Healing ◽

Antimicrobial Agents ◽

Healing Process ◽

Wound Dressings ◽

Wound Healing Process ◽

Delayed Wound Healing

Wound care is a major biomedical field that is challenging due to the delayed wound healing process. Some factors are responsible for delayed wound healing such as malnutrition, poor oxygen flow, smoking, diseases (such as diabetes and cancer), microbial infections, etc. The currently used wound dressings suffer from various limitations, including poor antimicrobial activity, etc. Wound dressings that are formulated from biopolymers (e.g., cellulose, chitin, gelatin, chitosan, etc.) demonstrate interesting properties, such as good biocompatibility, non-toxicity, biodegradability, and attractive antimicrobial activity. Although biopolymer-based wound dressings display the aforementioned excellent features, they possess poor mechanical properties. Gelatin, a biopolymer has excellent biocompatibility, hemostatic property, reduced cytotoxicity, low antigenicity, and promotes cellular attachment and growth. However, it suffers from poor mechanical properties and antimicrobial activity. It is crosslinked with other polymers to enhance its mechanical properties. Furthermore, the incorporation of antimicrobial agents into gelatin-based wound dressings enhance their antimicrobial activity in vitro and in vivo. This review is focused on the development of hybrid wound dressings from a combination of gelatin and other polymers with good biological, mechanical, and physicochemical features which are appropriate for ideal wound dressings. Gelatin-based wound dressings are promising scaffolds for the treatment of infected, exuding, and bleeding wounds. This review article reports gelatin-based wound dressings which were developed between 2016 and 2021.

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Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9674809 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Yan Xu ◽

Ze Lin ◽

Lei He ◽

Yanzhen Qu ◽

Liu Ouyang ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Platelet Rich Plasma ◽

Healing Process ◽

Cell Counting ◽

Wound Healing Process ◽

Hacat Cells ◽

Epithelial Regeneration

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.

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HvRNASET2 Regulate Connective Tissue and Collagen I Remodeling During Wound Healing Process

Frontiers in Physiology ◽

10.3389/fphys.2021.632506 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nicolò Baranzini ◽

Laura Pulze ◽

Gianluca Tettamanti ◽

Francesco Acquati ◽

Annalisa Grimaldi

Keyword(s):

Immune Response ◽

Wound Healing ◽

Muscle Tissue ◽

Tissue Regeneration ◽

Immune Modulation ◽

Healing Process ◽

Wound Healing Process ◽

Collagen Production

Several studies have recently demonstrated that the correct regeneration of damaged tissues and the maintaining of homeostasis after wounds or injuries are tightly connected to different biological events, involving immune response, fibroplasia, and angiogenetic processes, in both vertebrates and invertebrates. In this context, our previous data demonstrated that the Hirudo verbana recombinant protein rHvRNASET2 not only plays a pivotal role in innate immune modulation, but is also able to activate resident fibroblasts leading to new collagen production, both in vivo and in vitro. Indeed, when injected in the leech body wall, which represents a consolidated invertebrate model for studying both immune response and tissue regeneration, HvRNASET2 induces macrophages recruitment, fibroplasia, and synthesis of new collagen. Based on this evidence, we evaluate the role of HvRNASET2 on muscle tissue regeneration and extracellular matrix (ECM) remodeling in rHvRNASET2-injected wounded leeches, compared to PBS-injected wounded leeches used as control. The results presented here not only confirms our previous evidence, reporting that HvRNASET2 leads to an increased collagen production, but also shows that an overexpression of this protein might influence the correct progress of muscle tissue regeneration. Moreover, due to its inhibitory effect on vasculogenesis and angiogenesis, HvRNASET2 apparently interfere with the recruitment of the myoendothelial vessel-associated precursor cells that in turn are responsible for muscle regeneration during wound healing repair.

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Bioinspired mechanically active adhesive dressings to accelerate wound closure

Science Advances ◽

10.1126/sciadv.aaw3963 ◽

2019 ◽

Vol 5 (7) ◽

pp. eaaw3963 ◽

Cited By ~ 61

Author(s):

S. O. Blacklow ◽

J. Li ◽

B. R. Freedman ◽

M. Zeidi ◽

C. Chen ◽

...

Keyword(s):

Wound Healing ◽

Wound Closure ◽

Healing Process ◽

Skin Wound ◽

Wound Management ◽

In Vivo Studies ◽

Skin Wound Healing ◽

Accelerate Wound Healing

Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.

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