Upregulating mTOR/ERK signaling with leonurine for promoting angiogenesis and tissue regeneration in a full-thickness cutaneous wound model

2018 ◽  
Vol 9 (4) ◽  
pp. 2374-2385 ◽  
Author(s):  
Chenggui Wang ◽  
Zengjie Zhang ◽  
Tianzhen Xu ◽  
Yiting Lou ◽  
Qingqing Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Healing Process ◽  
Erk Signaling ◽  
Wound Healing Process ◽  
Erk Pathway ◽  
Full Thickness ◽  
Cutaneous Wound ◽  
Wound Model

LN promoted the angiogenesis of endothelial cells by activating the mTOR/ERK pathway, and efficiently enhanced the wound-healing processin vivo.

scholarly journals Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness

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.

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

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.

Icariin-Loaded Polyvinyl Alcohol/Agar Hydrogel: Development, Characterization, and In Vivo Evaluation in a Full-Thickness Burn Model

2019 ◽  
Vol 18 (3) ◽  
pp. 323-335 ◽  
Author(s):  
Varuna Naga Venkata Arjun Uppuluri ◽  
T. S. Shanmugarajan
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Polyvinyl Alcohol ◽  
Tissue Regeneration ◽  
Healing Process ◽  
Wound Healing Process ◽  
Full Thickness ◽  
Burn Wound ◽  
In Vivo Evaluation ◽  
Hydrogel Scaffolds

Tissue regeneration has become a promising strategy for repairing damaged skin tissues. Among the hydrogels for tissue regeneration applications, topical hydrogels have demonstrated great potential for use as 3D-scaffolds in the burn wound healing process. Currently, no report has been published specifically on icariin-loaded polyvinyl alcohol (PVA)/agar hydrogel on full-thickness burn wounds. In the present study, burn tissue regeneration based on biomimetic hydrogel scaffolds was used for repairing damaged extracellular matrix. Furthermore, a skin burn model was developed in rats, and the icariin-loaded PVA/agar hydrogels were implanted into the damaged portions. The regeneration of the damaged tissues with the help of the icariin-loaded hydrogel group exhibited new translucent skin tissues and repaired extracellular matrix, indicating that the hydrogel can enhance the wound healing process. Moreover, characterization studies such as X-ray diffraction, Fourier-transformed infrared spectroscopy, and differential scanning calorimetry reported the extent of compatibility between icariin and its polymers. Results of the field emission scanning electron microscopy images revealed the extent of the spread of icariin within the polymer-based hydrogel. Furthermore, the wound healing potential, confirmed by histopathological and histochemical findings at the end of 21 days, revealed the visual evidence for the biomimetic property of icariin-loaded PVA/agar hydrogel scaffolds with the extracellular matrix for tissue regeneration.

scholarly journals Effect of Polysaccharides from Bletilla striata on the Healing of Dermal Wounds in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chen Zhang ◽  
Yanan He ◽  
Zhejie Chen ◽  
Jinfeng Shi ◽  
Yan Qu ◽  
...  
Keyword(s):  
Health Care ◽  
Wound Healing ◽  
Healing Process ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Wound Healing Process ◽  
Skin Defect ◽  
Full Thickness ◽  
Bletilla Striata

Bletilla striata has been largely used in traditional folk medicine in China as a wound healing agent and to treat gastritis and several other health problems. Some studies have shown that plant polysaccharides may have the ability to promote wound healing. The aim of this work was to evaluate the wound healing activity of the polysaccharide extracted from Bletilla striata. Firstly, a Bletilla striata polysaccharide was extracted by water extraction and alcohol precipitation and characterized by Fourier transform infrared spectroscopy. The Bletilla striata polysaccharide was then tested for cell migration and proliferation using the mouse fibroblast cell line. Then, the Bletilla striata hydrogel was fabricated for acute wound health care of the mouse full-thickness excision. The results showed that the BSP enhanced the proliferation and migration of L929 cells. The superior wound healing capacity of the BSP hydrogel was demonstrated that it significantly accelerated the wound healing process in vivo in full-thickness skin defect wounded models. Compared to the saline group, the BSP hydrogel could accelerate wound healing and promote re-epithelialization and collagen deposition by means of TGF-β/Smad signal pathway activation. Taken together, BSP hydrogel would be a useful pharmaceutic candidate for acute cutaneous wound health care.

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

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.

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

Molecules ◽  
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.

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

2017 ◽  
Vol 751 ◽  
pp. 581-585 ◽  
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.

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

Polymers ◽  
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.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

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.

Influence of sensory neuropeptides on human cutaneous wound healing process

2014 ◽  
Vol 74 (3) ◽  
pp. 193-203 ◽  
Author(s):  
J. Chéret ◽  
N. Lebonvallet ◽  
V. Buhé ◽  
J.L. Carre ◽  
L. Misery ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Sensory Neuropeptides
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