The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process

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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Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms23020941 ◽

2022 ◽

Vol 23 (2) ◽

pp. 941

Author(s):

Valeska Ormazabal ◽

Estefanía Nova-Lampeti ◽

Daniela Rojas ◽

Felipe A. Zúñiga ◽

Carlos Escudero ◽

...

Keyword(s):

Type 2 Diabetes ◽

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Healing Process ◽

Human Mesenchymal Stem Cells ◽

Wound Healing Process ◽

Diabetes Mouse

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.

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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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Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness

Frontiers in Immunology ◽

10.3389/fimmu.2021.722469 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laryssa C. Manigat ◽

Mitchell E. Granade ◽

Suchet Taori ◽

Charlotte Anne Miller ◽

Luke R. Vass ◽

...

Keyword(s):

Wound Healing ◽

T Cell ◽

Healing Process ◽

Cell Activity ◽

Regulatory Function ◽

Burned Area ◽

Wound Healing Process ◽

Wound Model ◽

Complex Wound

The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint. In fact, the only significant phenotype previously observed in Dgka knockout (KO) mice is the enhancement of T-cell activity. Herein we reveal a novel, macrophage-specific, immune-regulatory function of DGKα. In bone marrow-derived macrophages (BMDMs) cultured from wild-type (WT) and KO mice, we observed increased responsiveness of KO macrophages to diverse stimuli that yield different phenotypes, including LPS, IL-4, and the chemoattractant MCP-1. Knockdown (KD) of Dgka in a murine macrophage cell line resulted in similar increased responsiveness. Demonstrating in vivo relevance, we observed significantly smaller wounds in Dgka-/- mice with full-thickness cutaneous burns, a complex wound healing process in which macrophages play a key role. The burned area also demonstrated increased numbers of macrophages. In a cortical stab wound model, Dgka-/- brains show increased Iba1+ cell numbers at the needle track versus that in WT brains. Taken together, these findings identify a novel immune-regulatory checkpoint function of DGKα in macrophages with potential implications for wound healing, cancer therapy, and other settings.

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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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Simple synthesis of multifunctional photosensitizers for mitochondrial and bacterial imaging and photodynamic anticancer and antibacterial therapy

Journal of Materials Chemistry B ◽

10.1039/d0tb01669a ◽

2020 ◽

Vol 8 (39) ◽

pp. 9035-9042

Author(s):

Ming-Yu Wu ◽

Li Liu ◽

Qian Zou ◽

Jong-Kai Leung ◽

Jia-Li Wang ◽

...

Keyword(s):

Wound Healing ◽

Antibacterial Therapy ◽

Healing Process ◽

Simple Synthesis ◽

Wound Healing Process

An isoquinolinium-based photosensitizer was developed for mitochondrial and bacterial imaging, and used in photodynamic anticancer and antibacterial therapy in a wound healing process in vivo.

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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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