A Novel Three-Polysaccharide Blend In Situ Gelling Powder for Wound Healing Applications

In this paper, alginate/pectin and alginate/pectin/chitosan blend particles, in the form of an in situ forming hydrogel, intended for wound repair applications, have been successfully developed. Particles have been used to encapsulate doxycycline in order to control the delivery of the drug, enhance its antimicrobial properties, and the ability to inhibit host matrix metalloproteinases. The presence of chitosan in the particles strongly influenced their size, morphology, and fluid uptake properties, as well as drug encapsulation efficiency and release, due to both chemical interactions between the polymers in the blend and interactions with the drug demonstrated by FTIR studies. In vitro antimicrobial studies highlighted an increase in antibacterial activity related to the chitosan amount in the powders. Moreover, in situ gelling powders are able to induce a higher release of IL-8 from the human keratinocytes that could stimulate the wound healing process in difficult-healing. Interestingly, doxycycline-loaded particles are able to increase drug activity against MMPs, with good activity against MMP-9 even at 0.5 μg/mL over 72 h. Such results suggest that such powders rich in chitosan could be a promising dressing for exudating wounds.

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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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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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RELEVANCE AND PERSPECTIVES OF EXPERIMENTAL WOUND MODELS IN WOUND HEALING RESEARCH

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i7.18276 ◽

2017 ◽

Vol 10 (7) ◽

pp. 57 ◽

Cited By ~ 1

Author(s):

Santram Lodhi ◽

Gautam P Vadnere

Keyword(s):

Wound Healing ◽

Search Engines ◽

Wound Repair ◽

Healing Process ◽

Chorioallantoic Membrane ◽

Tube Formation ◽

Wound Healing Process ◽

Burn Wound

The wound healing process consists of four highly integrated and overlapping phases: Hemostasis, inflammation, proliferation, and tissue remodeling. These phases and their biophysiological functions must occur in the proper sequence, at a specific time and continue for a specific duration at an optimal intensity. There are many factors that can affect wound healing which interferes with one or more phases in this process, thus causing improper or impaired tissue repair. This review was aimed to collect data and made a critical analysis. This will provide concise information regarding different models and parameters used for wound healing study. The data related to different wound models are collected using popular search engines as well as relevant science search engines and database including Google Scholar, Science Direct, and PubMed. A new drug substance can be evaluated for wound healing activity using different in vitro models such as cell culture, chick chorioallantoic membrane model, tube formation on metrigel and capillary growth model. The in vivo wound models such as incision, excision, dead space, burn wound, ischemic wound, and diabetic wound models are frequently used. Each model has specific importance. The limitations and advantages of each are described in this review. Although animal wound repair is an imperfect reflection of human wound healing and its clinical challenges, these models can be fundamental tools for the development of new approaches to rational wound therapy.

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PCL/Mesoglycan Devices Obtained by Supercritical Foaming and Impregnation

Pharmaceutics ◽

10.3390/pharmaceutics11120631 ◽

2019 ◽

Vol 11 (12) ◽

pp. 631 ◽

Cited By ~ 4

Author(s):

Paola Franco ◽

Raffaella Belvedere ◽

Emanuela Pessolano ◽

Sara Liparoti ◽

Roberto Pantani ◽

...

Keyword(s):

Wound Healing ◽

Biological Effects ◽

Healing Process ◽

Human Keratinocytes ◽

Skin Lesions ◽

Wound Healing Process ◽

Process Conditions ◽

Phosphate Buffered Saline

In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent with respect to MSG. The main objective is to produce an innovative topical device for application on skin lesions, promoting prolonged pro-resolving effects. The obtained device offers a protective barrier to ensure a favorable and sterilized environment for the wound healing process. The impregnation kinetics revealed that a pressure of 17 MPa, a temperature of 35 °C, and a time of impregnation of 24 h assured a proper foaming of PCL in addition to the impregnation of the maximum amount of MSG; i.e., 0.22 mgMSG/mgPCL. After a preliminary study conducted on PCL granules used as brought, the MSG impregnation was performed at the optimized process conditions also on a PCL film, produced by compression molding, with the final goal of producing medical patches. Comparing the dissolution profiles in phosphate buffered saline solution (PBS) of pure MSG and MSG impregnated on foamed PCL, it was demonstrated that the release of MSG was significantly prolonged up to 70 times. Next, we performed functional assays of in vitro wound healing, cell invasion, and angiogenesis to evaluate the biological effects of the PCL-derived MSG. Interestingly, we found the ability of this composite system to promote the activation of human keratinocytes, fibroblasts, and endothelial cells, as the main actors of tissue regeneration, confirming what we previously showed for the MSG alone.

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Systemic and topical administration of spermidine accelerates skin wound healing

Cell Communication and Signaling ◽

10.1186/s12964-021-00717-y ◽

2021 ◽

Vol 19 (1) ◽

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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Design of Portable Multicolor LED-Based Optical System for the Photobiomodulation Therapy on Wound Healing Process

Journal of Intelligent Systems with Applications ◽

10.54856/jiswa.202105159 ◽

2021 ◽

pp. 61-67

Author(s):

Nermin Topaloglu Avsar ◽

Ufuk Balkaya ◽

Ziysan Buse Yarali Cevik

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Optical System ◽

Healing Process ◽

Human Keratinocytes ◽

Light Therapy ◽

Optical Systems ◽

Wound Healing Process ◽

Noninvasive Treatment

Photobiomodulation is a practical and noninvasive treatment that triggers cell proliferation, cell differentiation, wound healing, new tissue formation, inflammation and pain reduction with low-level light therapy. Light-emitting diodes (LEDs) are energy-saving, affordable and safe alternatives to laser devices which are recently preferred in photobiomodulation. Although the wavelengths between 600-700 nm are most preferred ones, there is a lack of practical optical systems which study this mechanism in vitro with different wavelengths simultaneously. In this study, a portable and remotely controlled multicolor LED-based system was designed and tested on the wound healing process of human keratinocytes by irradiating the cells homogenously with 3 different wavelengths (460-475 nm as blue, 515-535 nm as green, and 585-595 nm as orange) on different experimental groups at the same time. Its proliferative and wound healing effect was evaluated with cell viability (MTT) analysis and cell migration (scratch) assay, respectively. It was observed that orange-LEDs were designated as the most triggering wavelength in terms of cell proliferation. Also, it was revealed with this device that different wavelengths can reach the intended accelerated wound healing process, so this optical system will be an advantageous design for future practical photobiomodulation studies in vitro.

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Hypotonic, Acidic Oxidizing Solution Containing Hypochlorous Acid (HClO) as a Potential Treatment of Hailey-Hailey Disease

Molecules ◽

10.3390/molecules24244427 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4427

Author(s):

Samantha Cialfi ◽

Salvatore Calabro ◽

Matteo Franchitto ◽

Azzurra Zonfrilli ◽

Isabella Screpanti ◽

...

Keyword(s):

Oxidative Stress ◽

Wound Healing ◽

Wound Repair ◽

Hypochlorous Acid ◽

Healing Process ◽

Skin Lesions ◽

Wound Healing Process ◽

Causative Role

Hailey–Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, characterized by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. Mutation of the Golgi Ca2+-ATPase ATP2C1 has been identified as having a causative role in Hailey–Hailey disease. HHD-derived keratinocytes have increased oxidative-stress that is associated with impaired proliferation and differentiation. Additionally, HHD is characterized by skin lesions that do not heal and by recurrent skin infections, indicating that HHD keratinocytes might not respond well to challenges such as wounding or infection. Hypochlorous acid has been demonstrated in vitro and in vivo to possess properties that rescue both oxidative stress and altered wound repair process. Thus, we investigated the potential effects of a stabilized form of hypochlorous acid (APR-TD012) in an in vitro model of HHD. We found that treatment of ATP2C1-defective keratinocytes with APR-TD012 contributed to upregulation of Nrf2 (nuclear factor (erythroid-derived 2)-like 2). Additionally, APR TD012-treatment restored the defective proliferative capability of siATP2C1-treated keratinocytes. We also found that the APR-TD012 treatment might support wound healing process, due to its ability to modulate the expression of wound healing associated cytokines. These observations suggested that the APR-TD012 might be a potential therapeutic agent for HHD-lesions.

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Design of Portable Multicolor LED-Based Optical System for the Photobiomodulation Therapy on Wound Healing Process

10.21203/rs.3.rs-354873/v2 ◽

2021 ◽

Author(s):

Nermin Topaloglu ◽

Ufuk Balkaya ◽

Ziyşan Buse Yaralı Çevik

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Optical System ◽

Healing Process ◽

Human Keratinocytes ◽

Light Therapy ◽

Optical Systems ◽

Wound Healing Process ◽

Invasive Treatment

Abstract Photobiomodulation is a practical and non-invasive treatment that triggers cell proliferation, cell differentiation, wound healing, new tissue formation, inflammation and pain reduction with low-level light therapy. Light-emitting diodes (LEDs) are energy-saving, affordable and safe alternatives to laser devices which are recently preferred in photobiomodulation. Although the wavelengths between 600-700 nm are most preferred ones, there is a lack of practical optical systems which study this mechanism in vitro with different wavelengths simultaneously. In this study, a portable and remotely controlled multicolor LED-based system was designed and tested on the wound healing process of human keratinocytes by irradiating the cells homogenously with 3 different wavelengths (460-475 nm as blue, 515-535 nm as green, and 585-595 nm as orange) on different experimental groups at the same time. Its proliferative and wound healing effect was evaluated with cell viability (MTT) analysis and cell migration (scratch) assay, respectively. It was observed that orange-LEDs were designated as the most triggering wavelength in terms of cell proliferation. Also, it was revealed with this device that different wavelengths can reach the intended accelerated wound healing process, so this optical system will be an advantageous design for future practical photobiomodulation studies in vitro.

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Portable Multicolor LED-Based System for the Photobiomodulation Therapy on Wound Healing Process In Vitro

10.21203/rs.3.rs-354873/v1 ◽

2021 ◽

Author(s):

Nermin Topaloglu ◽

Ufuk Balkaya ◽

Ziyşan Buse Yaralı Çevik

Keyword(s):

Cell Proliferation ◽

Wound Healing ◽

Healing Process ◽

Human Keratinocytes ◽

Light Therapy ◽

Optical Systems ◽

Wound Healing Process ◽

Invasive Treatment ◽

Light Emitting

Abstract Photobiomodulation is a practical and non-invasive treatment that triggers cell proliferation, cell differentiation, wound healing, new tissue formation, inflammation and pain reduction with low-level light therapy. Light-emitting diodes (LEDs) are energy-saving, affordable and safe alternatives to laser devices which are recently preferred in photobiomodulation. Although the wavelengths between 600–700 nm are most preferred ones, there is a lack of practical optical systems which study this mechanism in vitro with different wavelengths simultaneously. In this study, a portable and remotely controlled multicolor LED-based system was designed and tested on the wound healing process of human keratinocytes by irradiating the cells homogenously with 3 different wavelengths (460–475 nm as blue, 515–535 nm as green, and 585–595 nm as orange) on different experimental groups at the same time. Its proliferative and wound healing effect was evaluated with cell viability (MTT) analysis and cell migration (scratch) assay, respectively. It was observed that orange-LEDs were designated as the most triggering wavelength in terms of cell proliferation. Also, it was revealed with this device that different wavelengths can reach the intended accelerated wound healing process, so this optical system will be an advantageous design for future practical photobiomodulation studies in vitro.

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

10.21203/rs.3.rs-552400/v1 ◽

2021 ◽

Author(s):

Yan Xu ◽

Ze Lin ◽

Lei He ◽

Yanzhen Qu ◽

Ouyang Liu ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Platelet Rich Plasma ◽

Healing Process ◽

Wound Healing Process ◽

Hacat Cells ◽

Epithelial Regeneration ◽

Wound Healing Activity

Abstract Background: Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can be employed to 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. Results: We found that PRP-derived exosomes (PRP-Exos) effectively promoted the in vitro proliferation, migration, and wound healing activity of human immortalized keratinocytes (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. Conclusions: PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.

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