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 ◽  
...  

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.

2018 ◽  
Vol 9 (4) ◽  
pp. 2374-2385 ◽  
Author(s):  
Chenggui Wang ◽  
Zengjie Zhang ◽  
Tianzhen Xu ◽  
Yiting Lou ◽  
Qingqing Wang ◽  
...  

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


Author(s):  
Mengsi Ma ◽  
Yalan Zhong ◽  
Xulin Jiang

Prevention of the bacterial infection, acceleration of wound closure and promotion of skin regeneration are crucial in the wound healing process. In this work, the photothermal activity of the injectable...


2020 ◽  
pp. 484-490
Author(s):  
Chelombitko ◽  
Vasilieva ◽  
Fedorov ◽  
Kutyrev ◽  
Mazur

In this work, the wound healing potential of the extract from plerocercoids of gulltapeworm D. dendriticus was first estimated in the mouse full-thickness wound model. Both the evaluation of wound closure rate and the histological characteristics of the healing process were performed. In the course of the study, the effect of the extract on contraction and epithelization of wound was not revealed. At the same time, the results of histological analysis showed that the epidermis in the group of mice whose wounds were treated with the extract was less differentiated, and the newly formed connective tissue was less mature than in the group of control animals. In addition, differences were found in the composition of leukocyte infiltrate in the granulation tissue of experimental animals – there was a significant increase in the number of eosinophils and a tendency to a lower content of neutrophils. The results obtained indicate that treatment of wounds with extract from plerocercoids slows down the reparative processes, which, however, does not lead to significant changes in the rate of wound contraction. Perhaps, this difference is due to a change in the early stages of healing: extract stimulates eosinophils migration to the area of damage, while the number of neutrophils decreases. This can lead to a prolonged inflammatory phase and the associated slowdown in repair.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jiahui He ◽  
Zixi Zhang ◽  
Yutong Yang ◽  
Fenggang Ren ◽  
Jipeng Li ◽  
...  

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.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hamed Nosrati ◽  
Reza Aramideh Khouy ◽  
Ali Nosrati ◽  
Mohammad Khodaei ◽  
Mehdi Banitalebi-Dehkordi ◽  
...  

AbstractSkin is the body’s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.


2021 ◽  
Vol 30 (5) ◽  
pp. 350-370
Author(s):  
Ruan Na ◽  
Tian Wei

Objective: The burden of the management of problematic skin wounds characterised by a compromised skin barrier is growing rapidly. Almost six million patients are affected in the US alone, with an estimated market of $25 billion annually. There is an urgent requirement for efficient mechanism-based treatments and more efficacious drug delivery systems. Novel strategies are needed for faster healing by reducing infection, moisturising the wound, stimulating the healing mechanisms, speeding up wound closure and reducing scar formation. Methods: A systematic review of qualitative studies was conducted on the recent perspectives of nanotechnology in burn wounds management. Pubmed, Scopus, EMBASE, CINAHL and PsychINFO databases were all systematically searched. Authors independently rated the reporting of the qualitative studies included. A comprehensive literature search was conducted covering various resources up to 2018–2019. Traditional techniques aim to simply cover the wound without playing any active role in wound healing. However, nanotechnology-based solutions are being used to create multipurpose biomaterials, not only for regeneration and repair, but also for on-demand delivery of specific molecules. The chronic nature and associated complications of nonhealing wounds have led to the emergence of nanotechnology-based therapies that aim at facilitating the healing process and ultimately repairing the injured tissue. Conclusion: Nanotechnology-based therapy is in the forefront of next-generation therapy that is able to advance wound healing of hard-to-heal wounds. In this review, we will highlight the developed nanotechnology-based therapeutic agents and assess the viability and efficacy of each treatment. Herein we will explore the unmet needs and future directions of current technologies, while discussing promising strategies that can advance the wound-healing field


2021 ◽  
Vol 12 ◽  
Author(s):  
Laryssa C. Manigat ◽  
Mitchell E. Granade ◽  
Suchet Taori ◽  
Charlotte Anne Miller ◽  
Luke R. Vass ◽  
...  

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.


2019 ◽  
Vol 34 (8) ◽  
pp. 1171-1187
Author(s):  
Farnoush Oveissi ◽  
Naser Tavakoli ◽  
Mohsen Minaiyan ◽  
Mohammad Reza Mofid ◽  
Azade Taheri

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.


2019 ◽  
Vol 81 (4) ◽  
Author(s):  
Ulfah Anwar ◽  
Siti Pauliena Mohd Bohari

The aim of this research is to investigate the wound healing process in in vitro by combining the Manihot esculenta aqueous extract and therapeutic ultrasound. Firstly, the optimization seeding densities of HSF cell 1184 in six-well plate, and then followed by the scratch assay experiment. The scratched that made was treated with the remedial treatments (Manihot esculenta aqueous extract only; ascorbic acid+ therapeutic ultrasound; Manihot esculenta aqueous extract+ ascorbic acid; Manihot esculenta aqueous extract+ therapeutic ultrasound and also the combination of these three materials). The rate of wound closure was observed and analysed at a time interval of 0, 2, 4, 6, 8, 10 and 24 h by using image J software. Then, the cells viability were analysed using the MTT assay. The result showed that Manihot esculenta aqueous extract coupled with specific dose therapeutic ultrasound represents a significantly high rate of wound closure at 96.10 % with the cell numbers at 5.44×105 cells/mL when compared to the other combination therapy. The finding of this study revealed that Manihot esculenta aqueous extract 200 µg/mL and the therapeutic ultrasound specific dose (3 MHz, 300 mWatt/cm2, 50% in 5 min) have the potential in accelerating wound healing process of cells in in vitro.


2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li

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.


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