scholarly journals Injectable Self-Healing Adhesive pH-Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jiahui He ◽  
Zixi Zhang ◽  
Yutong Yang ◽  
Fenggang Ren ◽  
Jipeng Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endoscopic Treatment ◽  
Healing Process ◽  
Gelation Time ◽  
Type I ◽  
Self Healing ◽  
Ph Responsive ◽  
Gastric Hemorrhage ◽  
Wound Model ◽  
Arterial Bleeding

AbstractEndoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.

scholarly journals A Prototype Skin Substitute, Made of Recycled Marine Collagen, Improves the Skin Regeneration of Sheep

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1219
Author(s):  
Luca Melotti ◽  
Tiziana Martinello ◽  
Anna Perazzi ◽  
Ilaria Iacopetti ◽  
Cinzia Ferrario ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Sea Urchin ◽  
Healing Process ◽  
Skin Wound ◽  
Skin Substitute ◽  
Large Animal ◽  
Type I ◽  
Skin Wound Healing ◽  
Skin Adnexa

Skin wound healing is a complex and dynamic process that aims to restore lesioned tissues. Collagen-based skin substitutes are a promising treatment to promote wound healing by mimicking the native skin structure. Recently, collagen from marine organisms has gained interest as a source for producing biomaterials for skin regenerative strategies. This preliminary study aimed to describe the application of a collagen-based skin-like scaffold (CBSS), manufactured with collagen extracted from sea urchin food waste, to treat experimental skin wounds in a large animal. The wound-healing process was assessed over different time points by the means of clinical, histopathological, and molecular analysis. The CBSS treatment improved wound re-epithelialization along with cell proliferation, gene expression of growth factors (VEGF-A), and development of skin adnexa throughout the healing process. Furthermore, it regulated the gene expression of collagen type I and III, thus enhancing the maturation of the granulation tissue into a mature dermis without any signs of scarring as observed in untreated wounds. The observed results (reduced inflammation, better re-epithelialization, proper development of mature dermis and skin adnexa) suggest that sea urchin-derived CBSS is a promising biomaterial for skin wound healing in a “blue biotechnologies” perspective for animals of Veterinary interest.

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 Sufficient therapeutic effect of cryopreserved frozen adipose-derived regenerative cells on burn wounds

2018 ◽  
Author(s):  
Yasuhiko Kaita ◽  
Takehiko Tarui ◽  
Hideaki Yoshino ◽  
Takeaki Matsuda ◽  
Yoshihiro Yamaguchi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Therapeutic Effect ◽  
Healing Process ◽  
Control Group ◽  
Type I ◽  
Burn Wound ◽  
Burn Wounds ◽  
Burn Wound Healing ◽  
Significant Difference ◽  
Regenerative Cells

AbstractThe purpose of this study was to evaluate whether cryopreserved (frozen) adipose-derived regenerative cells (ADRCs) have a therapeutic effect on burn wound healing as well as freshly isolated (fresh) ADRCs.Full thickness burns were created on dorsum of nude mice and burn wound was excised. The wound was covered by artificial dermis with; (i) fresh ADRCs, (ii) frozen ADRCs, and (iii) PBS (control). The assessment for wound healing was performed by morphological, histopathological and immunohistochemical analyses.In vivo analyses exhibited the significant therapeutic effect of frozen ADRCs on burn wound healing up to the similar or higher level of fresh ADRCs. There were significant differences of wound closure, epithelized tissue thickness, and neovascularization between the treatment groups and control group. Although there was no significant difference of therapeutic efficacy between fresh ADRC group and frozen ADRC group, frozen ADRCs improved burn wound healing process in dermal regeneration with increased great type I collagen synthesis compared with fresh ADRCs.These findings indicate that frozen ADRCs allow us to apply not only quickly but also for multiple times, and the cryopreserved ADRCs could therefore be useful for the treatment of burn wounds in clinical settings.

scholarly journals Specific PKC βII inhibitor: one stone two birds in the treatment of diabetic foot ulcers

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li
Keyword(s):  
Wound Healing ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Wound Closure ◽  
Type I Diabetes ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peripheral Blood Flow ◽  
Type I ◽  
Diabetic Mice

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.

651 NLRP3 Activation Induced by Neutrophil Extracellular Traps Sustains Inflammatory Response in the Diabetic Wound

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S171-S172
Author(s):  
Dan Liu
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Healing Process ◽  
Dnase I ◽  
Cell Infiltration ◽  
Type I ◽  
Diabetic Wound ◽  
Extracellular Traps ◽  
Diabetic Wounds

Abstract Introduction Persistent inflammatory response in the diabetic wound impairs the healing process, resulting in significant morbidity and mortality. Mounting evidence indicates that the activation of NLRP3 inflammasome in macrophages (MF) contributes to the sustained inflammatory response and impaired wound healing associated with diabetes. However, the main trigger of NLRP3 inflammasome in the wounds is not known. Neutrophils, as sentinels of the innate immune system and key stimulators of MF, are immune cells that play the main role in the early phase of healing. Neutrophils release extracellular traps (NETs) as defense against pathogens. On the other hand, NETs induce tissue damage. NETs have been detected in the diabetic wound and implicated in the impaired healing process, but the mechanism of NETs suspend wound healing are elusive. Methods WB, immunofluorescence and immunocoprecipitation were used to detect the expression of NETs, NLRP3 inflammasome and IL-1b in diabetic foot ulcer wounds and the expression and activation of NLRP3 inflammsome after lowering the level of NETs. The role of NETs in activating macrophage inflammsome was verified and its mechanism was explored. Induced type I diabetic rats by STZ injection to detect the expression of NETs in the wound and observe the effects of exogenous DNase I on the expression of inflammasome and IL-1b in the wound, inflammatory cell infiltration and wound healing. Results NLRP3 and NETs are elevated in human and rat diabetic wounds. NETs overproduced in the diabetic wounds triggered NLRP3 inflammasome activation and IL-1b release. NETs up-regulated NLRP3 and pro-IL-1b levels via the TLR-4/TLR-9/NF-kB signalling pathway. NETs elicited ROS, which facilitated the association between NLRP3 and TXNIP, and activated the NLRP3 inflammasome. DNase I alleviated the activation of NLRP3 inflammasome, regulated the immune cell infiltration, and accelerated wound healing. Conclusions NETs contribute to the activation of NLRP3 inflammasome and sustained inflammatory response in the diabetic wound. NET digestion by DNase I alleviated the activation of NLRP3 inflammasome and accelerated wound healing. Applicability of Research to Practice

Two-Stage Patterned Cell-Based Treatments for Skin Regeneration

2020 ◽  
Vol 16 (12) ◽  
pp. 1740-1754
Author(s):  
Chih-Long Chen ◽  
Chieh-Yi Tsai ◽  
Yu-Shan Chen ◽  
Teng-Yen Lin ◽  
Yi-Jung Hsu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Wound Closure ◽  
Network Formation ◽  
Therapeutic Option ◽  
Healing Process ◽  
Skin Regeneration ◽  
Two Stage ◽  
Wound Model ◽  
Fetal Wound

During the process of wound healing, avoiding the formation of aligned collagen fibrils and subsequent scarring has become the focus of numerous research efforts. However, the goal of regeneration of native or scar-free skin remains a challenge. The complex and equivocal connection between inflammation and regeneration within the process of healing contributes to unsatisfactory treatment outcomes. Inspired by the scarless repair observed in fetal wound healing, we create a two-stage treatment combining the hydrocolloid dressing to attenuate the immune response in the initial three days, and the biomimetic cell-laden hydrogel to improve skin regeneration, which meet the specific needs of each stage in the healing process. To further accelerate the skin regeneration, the patterned cell-laden hydrogels were fabricated by photo-mask based photolithography technique. The efficacy and possible mechanisms of skin regeneration using this patterned cell-laden hydrogel therapy was investigated. Results show that these two-stage patterned cell-laden treatments were able to promote vascular network formation, accelerate wound closure, decrease scar formation, increase tissue regeneration and restore structure and mechanical properties of the skin in a full-thickness murine wound model. These data suggest that our patterned cell-based two-stage treatments can be used as a promising therapeutic option for wound healing by accelerating skin tissue regeneration.

Glucocorticoid-induced contractility and F-actin content of human lung fibroblasts in three-dimensional culture

2000 ◽  
Vol 278 (1) ◽  
pp. L13-L18 ◽  
Author(s):  
Hiroyuki Miki ◽  
Tadashi Mio ◽  
Sonoko Nagai ◽  
Yuma Hoshino ◽  
Takeo Tsutsumi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Lung ◽  
Healing Process ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Wound Healing Process ◽  
Architectural Distortion ◽  
Type I ◽  
Dependent Manner ◽  
Human Lung Fibroblast

Fibroblast contractility plays a useful role in the wound healing process but contributes to architectural distortion in the lungs. Glucocorticoids (GCs) have been reported to reduce dermal fibroblast contractility, which may result in delaying wound healing, but the effects on lung fibroblasts are unknown. In this study, we examined how human lung fibroblast contractility is altered in the presence of GCs. Lung fibroblast cell lines ( n = 5) were established from normal parts of surgically resected lung tissue. The effects of GCs on contractility were investigated with a type I collagen gel contraction assay. Filamentous actin (F-actin) content was detected by confocal microscopy and measured with a fluorescent phalloidin binding assay. GCs augmented fibroblast contraction in a concentration-dependent manner, with an approximate EC50 of 1.8 × 10−8 M, whereas other steroid derivatives had no effects. GC contractility needed de novo protein synthesis. The GC-induced increase in contractility was found to be consistent with an increase in F-actin content. In conclusion, lung fibroblast contractility was enhanced with GCs through an upregulation of lung fibroblast F-actin.

scholarly journals Effectiveness of Aqueous Extract of Marine Baitworm Marphysa moribidii Idris, Hutchings and Arshad, 2014 (Annelida, Polychaeta), on Acute Wound Healing Using Sprague Dawley Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Hannah Syahirah Rapi ◽  
Nor ‘Awatif Che Soh ◽  
Nurul Shahirah Mohd Azam ◽  
M. Maulidiani ◽  
Suvik Assaw ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Skin Irritation ◽  
Wound Healing Process ◽  
Histopathological Analysis ◽  
Pharmaceutical Drugs ◽  
Sprague Dawley ◽  
Normal Wound Healing ◽  
Wound Model ◽  
Ability To Regenerate

Wound healing is a well-coordinated process that restores skin integrity upon injury. However, some wound treatment poses harmful effects on the skin, which delay the normal wound healing process. Marphysa moribidii, a marine baitworm or polychaete, represents unique ability to regenerate posterior segment after injury, which may be beneficial in the wound healing treatment. The effectiveness of the polychaete as wound healing treatment was discovered through skin irritation, microbial testing, animal wound model, and chemical identifications. Three polychaete extracts (PE) emulsifying ointment (0.1%, 0.5%, and 1.0%) were topically applied to the full thickness wound model once daily for 14 days. Interestingly, PE 1.0% revealed the most rapid wound healing effects as compared to other treatments, including gamat (sea cucumber) oil (15% w/v) and acriflavine (0.1% w/v). Histopathological analysis using Masson’s trichrome staining further confirms that PE treated wound exhibited minimal scar, high collagen deposition, and the emergence of neovascularisation. The extract also displayed a minimum inhibitory concentration (MIC) of 0.4 g/ml against Escherichia coli and absence of skin irritation, infectious bacteria, and heavy metals from the extract. Moreover, chemical compounds such as alkaloid, flavonoid, amino acids, and organic acid were detected in M. moribidii extracts, which could contribute to wound healing activity. In conclusion, this study further justifies the beneficial use of polychaete in treating wound healing and could be developed as a novel bioactive agent in nutraceuticals and pharmaceutical drugs.

scholarly journals EVALUATION OF WOUND HEALING ACTIVITY OF POLYHERBAL FORMULATION

2017 ◽  
Vol 9 (6) ◽  
pp. 12
Author(s):  
Madhuri A. Theng ◽  
G. R. Sitaphale ◽  
K. R. Biyani
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Soxhlet Extraction ◽  
Wound Healing Process ◽  
Burn Wound ◽  
Butea Monosperma ◽  
Polyherbal Formulation ◽  
Wound Model ◽  
Acacia Arabica ◽  
Wound Healing Activity

Objective: The present study describes the anti-microbial acivity of Acacia arabica and Butea monosperma bark extract.Methods: For this purpose aqueous extract of bark were prepared by “Soxhlet extraction method”. The experimentally induced burn wound model in rats by “Excision method”.Results: As a result of this study it was found that the extract of bark generally revealed antimicrobial and wound healing activity.Conclusion: The result of the study suggest that the Acacia arabica and Butea monosperma bark of polyherbal gel effective in accelerating wound healing process.

scholarly journals Original Research: Adipose-derived stem cells from younger donors, but not aging donors, inspire the host self-healing capability through its secreta

2016 ◽  
Vol 242 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Ning Ma ◽  
Chenhui Qiao ◽  
Weihua Zhang ◽  
Hong Luo ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Associated Factors ◽  
Original Research ◽  
Adipose Derived Stem Cells ◽  
Self Healing ◽  
Cutaneous Wound ◽  
Epidermal Keratinocyte ◽  
Wound Model ◽  
Keratinocyte Stem Cells

Adipose-derived stem cells demonstrate promising effects in promoting cutaneous wound healing, but the mechanisms are still not well defined and contradictory views are still debatable. In the present research, we established a mouse cutaneous wound model and investigated the effects of adipose-derived stem cells in wound healing. Adipocyte, adipose-derived stem cells, and epidermal keratinocyte stem cells were isolated from younger and aged donors according to the standard protocol. The conditioned medium either from adipose-derived stem cells or from adipocytes was used to treat epidermal keratinocyte cells. The results showed that adipocytes or adipose-derived stem cells isolated from younger donors demonstrated mild advantage over those cells isolated from aging donors. Adipose-derived stem cells showed stronger stimuli than adipocytes, and the adipose-derived stem cells or adipocytes from younger donors enabled to support higher growth rate of keratinocyte stem cells. The invasion of vasculature was observed at day 10 after posttransplantation in the mice bearing the keratinocyte stem cells or combination of keratinocyte stem cells with adipose-derived stem cells; however, simply inoculating keratinocyte stem cells from aging donors did not result in vasculature formation. Adipose-derived stem cells isolated from younger donors were able to inspire the host’s self-healing capabilities, and age-associated factors should be taken into consideration when designing a feasible therapeutic treatment for skin regeneration.

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