scholarly journals Demonstration of re-epithelialization in a bioprinted human skin equivalent wound model

2020 ◽  
Author(s):  
Carlos Poblete Jara ◽  
Carolina Motter Catarino ◽  
Yuguo Lei ◽  
Lício Augusto Velloso ◽  
Pankaj Karande ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Skin ◽  
Wound Closure ◽  
Skin Wound ◽  
Skin Equivalent ◽  
Surrounding Tissue ◽  
Skin Wound Healing ◽  
Over The Top ◽  
Human Skin Equivalent

AbstractObjectiveThe development of an in vitro platform for modeling human skin injury and the re-epithelization process.ApproachA fibrin provisional matrix (FPM) was installed into a wound facsimile of a bioprinted human skin equivalent (HSE). A mixture of plasma-derived fibrinogen-containing factor XIII, fibronectin, thrombin, and macrophages (an FPM “bioink”) was extruded into the wound site. The surrounding in vitro tissue culture became a source of keratinocytes to achieve wound closure by a re-epithelialization process signaled by the FPM.ResultsAn in vitro analog of wound closure and re-epithelialization by keratinocytes occurred over the FPM after a normal migration initiation at 3 days.InnovationA physiologic mixture of macrophage/fibrinogen/fibronectin that supports macrophage differentiation was applied to a mechanically wounded, bioprinted dermal tissue. We developed a transitional culture medium to mimic the changing microenvironment during the initial phases of wound healing. As a reference, we temporally compared our in vitro model with a murine skin wound healing.ConclusionThis co-culture model was shown to temporally synchronize a re-epithelization process for initiation of keratinocyte migration from a surrounding tissue and the migration process over the top of an FPM. A future study of the analogous subepithelial healing pathway is envisioned using the same in vitro bioprinted tissue study platform for co-culture of keratinocytes, melanocytes, fibroblasts, endothelial cells, and macrophages using more specialized FPMs.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

scholarly journals Bioinspired mechanically active adhesive dressings to accelerate wound closure

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw3963 ◽  
Author(s):  
S. O. Blacklow ◽  
J. Li ◽  
B. R. Freedman ◽  
M. Zeidi ◽  
C. Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Management ◽  
In Vivo Studies ◽  
Skin Wound Healing ◽  
Accelerate Wound Healing

Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.

scholarly journals Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 222
Author(s):  
Suneel Kumar ◽  
Yuying Tan ◽  
Francois Berthiaume
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Substance P ◽  
Wound Closure ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Male And Female ◽  
Low Serum

Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10−7 M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.

Desmosomal distribution in the epidermis of a non-contracting human skin equivalent

1992 ◽  
Vol 50 (1) ◽  
pp. 896-897
Author(s):  
L.X. Oakford ◽  
S.D. Dimitrijevich ◽  
R. Gracy
Keyword(s):  
Human Skin ◽  
Basal Layer ◽  
Skin Equivalent ◽  
Tissue Component ◽  
Intact Skin ◽  
Similar Sequence ◽  
Sequence Of Events ◽  
Suprabasal Keratinocytes ◽  
Human Skin Equivalent

In intact skin the epidermal layer is a dynamic tissue component which is maintained by a basal layer of mitotically active cells. The protective upper epidermis, the stratum corneum, is generated by differentiation of the suprabasal keratinocytes which eventually desquamate as anuclear comeocytes. A similar sequence of events is observed in vitro in the non-contracting human skin equivalent (HSE) which was developed in this lab (1). As a part of the definition process for this model of living skin we are examining its ultrastructural features. Since desmosomes are important in maintaining cell-cell interactions in stratified epithelia their distribution in HSE was examined.

Fabrication of gelatin/sodium alginate-poly (3-hydroxybutyric acid) bilayer electrospun biosheet as wound healing material in nursing care on pediatric fracture surgery

2020 ◽  
pp. 152808372097634
Author(s):  
Daiqi Jiang ◽  
Zaiju Tong ◽  
Lingjun Peng ◽  
Lingzhi Zhang ◽  
Qianzi Ruan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Sodium Alginate ◽  
Wound Closure ◽  
Skin Wound ◽  
Tissue Formation ◽  
Hydroxybutyric Acid ◽  
Physiochemical Properties ◽  
Pediatric Fracture ◽  
Fracture Surgery

Novel the bilayered electrospun biosheet with rapid cell mimiciking and proliferative efficacy will be suitable for wound healing application. The optimized concentration of gelatin (G) and sodium alginate (A) biosheet with nanofibrous Poly (3-hydroxybutyric acid) (P) as a bilayered elctrospun matrix through electrospinning. The engineered GAP bilayered biosheet involves tissue formation at extra cellular matrix (ECM) which further characterized its function in vitro and invivo. Here we fabricated GAP which exhibit better physiochemical properties, biological and mechanical properties with superior prosomes it enhance air passable at skin wounds. The Bilayered biosheet matrix possess better biocompatibility, cell adherence, fructuous and cell to cell interactions evaluated using cell lines. Furthermore, GAP bilayered matrix regulates growth factors to attain maximum wound closure efficiency during invivo. Thus, the fabricated GAP electrospun biosheet would be a possible wound dressing for skin wound applications.

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.

Development of a Three-Dimensional Human Skin Equivalent Wound Model for Investigating Novel Wound Healing Therapies

2010 ◽  
Vol 16 (5) ◽  
pp. 1111-1123 ◽  
Author(s):  
Yan Xie ◽  
Simone C. Rizzi ◽  
Rebecca Dawson ◽  
Emily Lynam ◽  
Sean Richards ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Skin ◽  
Three Dimensional ◽  
Skin Equivalent ◽  
Wound Model ◽  
Human Skin Equivalent

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.

Different Trypanosoma cruzi calreticulin domains mediate migration and proliferation of fibroblasts in vitro and skin wound healing in vivo

2018 ◽  
Vol 310 (8) ◽  
pp. 639-650 ◽  
Author(s):  
Jose Ignacio Arias ◽  
Natalia Parra ◽  
Carolina Beato ◽  
Cristian Gabriel Torres ◽  
Christopher Hamilton-West ◽  
...  
Keyword(s):  
Wound Healing ◽  
Trypanosoma Cruzi ◽  
Skin Wound ◽  
Skin Wound Healing

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

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