Wound Healing - New insights into Ancient Challenges (original) (raw)
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The Use of Amniotic Membrane in the Management of Complex Chronic Wounds
Wound Healing - New insights into Ancient Challenges, 2016
Chronic wounds do not follow the usual wound healing process; instead, they are stuck in the inflammatory or proliferative phase. This is particularly evident in large, massive wounds with considerable tissue loss, which become senescent and do not epithelialize. In these wounds, we need to remove all the factors that prevent or delay normal wound healing. After that, soft tissue granulation is stimulated by local negative pressure therapy. Lastly, after the granulation is completed, the epithelialization process must be activated. Although a plethora of wound dressings and devices are available, chronic wounds persist as a unresolved medical concern. We have been using frozen amniotic membrane (AM) to treat this type of wounds with good results. Our studies have shown that AM is able to induce epithelialization in large wounds that were unable to epithelialize. AM induces several signaling pathways involved in cell migration and/or proliferation. Among those, we can highlight the mitogen-activated protein kinase (MAPK) and Jun N-terminal kinase (JNK) signaling pathways. Additionally, AM is able to selectively antagonise the anti-proliferative effect of TGFß by modifying its genetic program on keratinocytes. The combined effect of AM on keratinocytes, promoting cell proliferation/migration and antagonising TGFß-effect, is the perfect combination allowing chronic wounds to progress into epithelialization.
Frontiers in Bioengineering and Biotechnology, 2021
The application of amniotic membrane (AM) on chronic wounds has proven very effective at resetting wound healing, particularly in re-epithelialization. Historically, several aspects of AM effect on wound healing have been evaluated using cell models. In keratinocytes, the presence of AM induces the activation of mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) pathways, together with the high expression of c-Jun, an important transcription factor for the progression of the re-epithelialization tongue. In general, the levels of transforming growth factor (TGF)-β present in a wound are critical for the process of wound healing; they are elevated during the inflammation phase and remain high in some chronic wounds. Interestingly, the presence of AM, through epidermal growth factor (EGF) signaling, produces a fine-tuning of the TGF-β signaling pathway that re-conducts the stalled process of wound healing. However, the complete suppression of TGF-β signaling has p...
Amniotic membrane induces epithelialization in massive posttraumatic wounds
Wound Repair and Regeneration, 2010
Large-surface or deep wounds often become senescent in the inflammatory or proliferation stages and cannot progress to reepithelialization. This failure makes intervention necessary to provide the final sealing epithelial layer. The best current treatment is autologous skin graft, although there are other choices such as allogenic or autologous skin substitutes and synthetic dressings. Amniotic membrane (AM) is a tissue of interest as a biological dressing due to its biological properties and immunologic characteristics. It has low immunogenicity and beneficial reepithelialization effects, with antiinflammatory, antifibrotic, antimicrobial, and nontumorigenic properties. These properties are related to its capacity to synthesize and release cytokines and growth factors. We report the use of AM as a wound dressing in two patients with large and deep traumatic wounds. Negative pressure wound therapy followed by AM application was capable of restoring skin integrity avoiding the need for skin graft reconstruction. AM induced the formation of a well-structured epidermis. To understand this effect, we designed some assays on human keratinocyte-derived HaCaT cells. AM treatment of HaCaT induced ERK1/2 and SAP/JNK kinases phosphorylation and c-jun expression, a gene critical for keratinocytes migration; however, it did not affect cell cycle distribution. These data suggest that AM substantially modifies the behavior of keratinocytes in chronic wounds, thereby allowing effective reepithelialization.
International Journal of Molecular Sciences
Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-β (TFG-β) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-β1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation ...
PLOS ONE, 2015
Background Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. Methods and Findings To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. Conclusions The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization.
Effect of freeze dried bovine amniotic membrane extract on full thickness wound healing
Archives of Pharmacal Research, 2013
This study explored the feasibility of development of solubilized amniotic membrane extract (AME) as a potential wound healing substrate with improved efficacy. Bovine amniotic membrane was extracted using a mixture of acetic acid and 2-mercaptopropionic acid under sonication, which was followed by the frozen, and then lyophilized processes. The effects of AME on cell migration and growth properties were evaluated from 0 to 24 h of post injury using primary human foreskin fibroblast monolayer culture with one line scratch as an in vitro wound model. Its wound healing efficacy and scar preventive effects were investigated using whole thickness biopsy punch (8 mm) wound model obtained from rabbit ear. Intra dermal injections of AME fluid (10 ll of 1.2 lg/ll) on four wound sites were performed at 1 h pre injury, post 1, 2 and 3 day. The processes and levels of re-epithelialization and dermal regeneration were examined through histological assessment with HE staining. In cell migration study conducted at 24 h post injury, AME (1.7 lg/ml) treated cells significantly increased wound closure with 54.9 % compared to control. Histological image analysis on AME treated wound sites at 36 days post injury showed properly developed epidermal basal cell layers and weave-like dermal collagen bundles, whereas those of untreated control skin showed over-proliferation of epidermis and aggregated collagen bundles with defected dermal regeneration. The results of this study verified the feasibility of dermal injections of freeze dried AME as a potential wound healing substrate which can promote epidermal and dermal regeneration, while avoiding undesirable hyper-proliferation of damaged tissue.
Amniotic Membrane in the Treatment of Hard-to-Heal Wounds
IntechOpen eBooks, 2024
Chronic or hard to heal wounds result in protracted healing trajectories that place a significant burden on both the patient and the society. Wounds that are classified as hard to heal often result in management challenges for which adjunctive therapies are indicated to assist in the healing process. Adjunctive therapy in wound management refers to additional treatment methods that are used to support or enhance the effectiveness of the primary wound therapy. Several types of adjunctive therapies are available, each with its own merit. Adjunctive therapy is used in conjunction with standard wound care practices to promote healing and assist in preventing complications. In the race against increasing costs, an aging population and increased incidence and prevalence of debilitating co-morbid conditions like diabetes, clinicians need to be innovative in the utilization of recourses that could assist in improving outcomes for patients that suffer from chronic or hard to heal wounds. The use of adjunctive therapy like amniotic membrane (AM) is supported by elevated levels of evidence in that this therapy could, when incorporated into an evidence-based standard of care regime, support or enhance the effectiveness of care and improve outcomes for patients suffering with chronic or hard to heal wounds. The following sections will give an overview of chronic wound healing, where in the treatment algorithm an adjunctive therapy like amniotic membrane could be utilized as well as the practical application of amniotic membrane.
Amniotic membrane stimulates cell migration by modulating Transforming Growth Factor-β signaling
Journal of tissue engineering and regenerative medicine, 2017
Keratinocyte migration is a mandatory aspect of wound-healing. We have previously shown that Amniotic Membrane (AM) applied to chronic wounds assists healing through a process resulting in overexpression of c-Jun at the wound's leading edge. Also, we have demonstrated that amniotic membrane modifies the genetic program induced by TGF-ß in chronic wounds. In this paper, we used a scratch assay of Mv1Lu and HaCaT cells to examine the influence of AM application on the underlying signaling during scratch closure. AM-application induced c-Jun phosphorylation at the leading-edge of scratch wounds in a process dependent on MAPK and JNK signaling. Strikingly, when the TGF-ß-dependent Smad-activation inhibitor SB431542 was used together with AM, migration improvement was partially restrained, while addition of TGF-ß had a synergistic effect on the AM induced cell migration. Moreover, antagonizing TGF-ß with specific antibodies in both cell lines or knocking out TGF-ß receptors in Mv1Lu ...