Wound Healing and Tissue Regeneration

A special issue of Journal of Developmental Biology (ISSN 2221-3759).

Deadline for manuscript submissions: closed (31 October 2015) | Viewed by 86473

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Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
Interests: Akt family of kinases; angiogenesis; wound healing; mitochondrial function and control

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Published Papers (8 papers)

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Research

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3549 KiB  
Article
Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site
by Jean-Christophe Tille, Sarra De Valence, Delia Mandracchia, Benjamin Nottelet, Francesco Innocente, Robert Gurny, Michael Möller and Beat H. Walpoth
J. Dev. Biol. 2016, 4(1), 11; https://doi.org/10.3390/jdb4010011 - 20 Feb 2016
Cited by 8 | Viewed by 6528
Abstract
Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some extent, [...] Read more.
Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some extent, be useful to forecast results for vascular prostheses. We compared biological and histological responses to scaffolds in different implantation sites. Polycaprolactone (PCL), paclitaxel-loaded PCL (PCL-PTX) and dexamethasone-loaded PCL (PCL-DXM) electrospun scaffolds were implanted subcutaneously and in an infrarenal abdominal aortic model in rats for up to 12 weeks. At the conclusion of the study, a histological analysis was performed. Cellular graft invasion revealed differences in the progression of cellular infiltration between PCL-PTX and PCL/PCL-DXM groups in both models. Cell infiltration increased over time in the aortic model compared to the subcutaneous model for all groups. Cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation in all groups and models over time. Macrophages and giant cells increased in the PCL aortic model; whereas in the subcutaneous model these cell types increased only after three weeks or even decreased in the drug-eluting PCL groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. The subcutaneous implant model can be used for screening, especially when drug-eluting effects are studied. However, major histological differences were observed in cell type reaction and depth of cell penetration compared to the aortic model. Our results demonstrate that the implantation site is a critical determinant of the biological response. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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13672 KiB  
Article
Regeneration of the Epiphysis Including the Articular Cartilage in the Injured Knees of the Lizard Podarcis muralis
by Lorenzo Alibardi
J. Dev. Biol. 2015, 3(2), 71-89; https://doi.org/10.3390/jdb3020071 - 12 May 2015
Cited by 10 | Viewed by 6654
Abstract
Cartilage regeneration is massive during tail regeneration in lizards but little is known about cartilage regeneration in other body regions of the skeleton. The recovery capability of injured epiphyses of femur and tibia of lizard knees has been studied by histology and 5BrdU [...] Read more.
Cartilage regeneration is massive during tail regeneration in lizards but little is known about cartilage regeneration in other body regions of the skeleton. The recovery capability of injured epiphyses of femur and tibia of lizard knees has been studied by histology and 5BrdU immunohistochemistry in lizards kept at high environmental temperatures. Lizard epiphyses contain a secondary ossified center of variable extension surrounded peripherally by an articular cartilage and basally by columns of chondrocytes that form the mataphyseal or growth plate. After injury of the knee epiphyses, a broad degeneration of the articular cartilage during the first days post-injury is present. However a rapid regeneration of cartilaginous tissue is observed from 7 to 14 days post-injury and by 21 days post-lesions, a large part of the epiphyses are reformed by new cartilage. Labeling with 5BrdU indicates that the proliferating cells are derived from both the surface of the articular cartilage and from the metaphyseal plate, two chondrogenic regions that appear proliferating also in normal, uninjured knees. Chondroblasts proliferate by interstitial multiplication forming isogenous groups with only a scant extracellular matrix that later increases. The high regenerative power of lizard articular cartilage appears related to the permanence of growing cartilaginous centers in the epiphyses of long bones such as those of the knee during adulthood. It is likely that these regions contain resident stem cells that give rise to new chondroblasts of the articular and metaphyseal cartilage during most of the lizard’s lifetime, but can produce an excess of cartilaginous tissues when stimulated by the lesion. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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4653 KiB  
Article
Observations on Lumbar Spinal Cord Recovery after Lesion in Lizards Indicates Regeneration of a Cellular and Fibrous Bridge Reconnecting the Injured Cord
by Lorenzo Alibardi
J. Dev. Biol. 2014, 2(4), 210-229; https://doi.org/10.3390/jdb2040210 - 19 Dec 2014
Cited by 9 | Viewed by 6740
Abstract
The lumbar spinal cords of lizards were transected, but after the initial paralysis most lizards recovered un-coordinated movements of hind limbs. At 25-45 days post-lesion about 50% of lizards were capable of walking with a limited coordination. Histological analysis showed that the spinal [...] Read more.
The lumbar spinal cords of lizards were transected, but after the initial paralysis most lizards recovered un-coordinated movements of hind limbs. At 25-45 days post-lesion about 50% of lizards were capable of walking with a limited coordination. Histological analysis showed that the spinal cord was transected and the ependyma of the central canal formed two enlargements to seal the proximal and distal ends of the severed spinal cord. Glial and few small neurons were formed while bridge axons crossed the gap between the proximal and the distal stumps of the transected spinal cord as was confirmed by retrograde tract-tracing technique. The bridging fibers likely derived from interneurons located in the central and dorsal grey matter of the proximal spinal cord stump suggesting they belong to the local central locomotory pattern generator circuit. The limited recovery of hind limb movements may derive from the regeneration or sprouting of short proprio-spinal axons joining the two stumps of the transected spinal cord. The present observations indicate that the study on spinal cord regeneration in lizards can give insights on the permissive conditions that favor nerve regeneration in amniotes. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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Article
A Novel Three-Dimensional Wound Healing Model
by Zhuo J. Chen, Jessica P. Yang, Benjamin M. Wu and Bill Tawil
J. Dev. Biol. 2014, 2(4), 198-209; https://doi.org/10.3390/jdb2040198 - 19 Dec 2014
Cited by 26 | Viewed by 11273
Abstract
Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds [...] Read more.
Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitationit lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more complex wound healing assay than existing wound models. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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Review

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638 KiB  
Review
Signalling by Transforming Growth Factor Beta Isoforms in Wound Healing and Tissue Regeneration
by Richard W.D. Gilbert, Matthew K. Vickaryous and Alicia M. Viloria-Petit
J. Dev. Biol. 2016, 4(2), 21; https://doi.org/10.3390/jdb4020021 - 22 Jun 2016
Cited by 114 | Viewed by 13259
Abstract
Transforming growth factor beta (TGFβ) signalling is essential for wound healing, including both non-specific scar formation and tissue-specific regeneration. Specific TGFβ isoforms and downstream mediators of canonical and non-canonical signalling play different roles in each of these processes. Here we review the role [...] Read more.
Transforming growth factor beta (TGFβ) signalling is essential for wound healing, including both non-specific scar formation and tissue-specific regeneration. Specific TGFβ isoforms and downstream mediators of canonical and non-canonical signalling play different roles in each of these processes. Here we review the role of TGFβ signalling during tissue repair, with a particular focus on the prototypic isoforms TGFβ1, TGFβ2, and TGFβ3. We begin by introducing TGFβ signalling and then discuss the role of these growth factors and their key downstream signalling mediators in determining the balance between scar formation and tissue regeneration. Next we discuss examples of the pleiotropic roles of TGFβ ligands during cutaneous wound healing and blastema-mediated regeneration, and how inhibition of the canonical signalling pathway (using small molecule inhibitors) blocks regeneration. Finally, we review various TGFβ-targeting therapeutic strategies that hold promise for enhancing tissue repair. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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247 KiB  
Review
Beyond the Mammalian Heart: Fish and Amphibians as a Model for Cardiac Repair and Regeneration
by Kyle Jewhurst and Kelly A. McLaughlin
J. Dev. Biol. 2016, 4(1), 1; https://doi.org/10.3390/jdb4010001 - 23 Dec 2015
Cited by 12 | Viewed by 7327
Abstract
The epidemic of heart disease, the leading cause of death worldwide, is made worse by the fact that the adult mammalian heart is especially poor at repair. Damage to the mammal heart—such as that caused by myocardial infarction—leads to scarring, resulting in cardiac [...] Read more.
The epidemic of heart disease, the leading cause of death worldwide, is made worse by the fact that the adult mammalian heart is especially poor at repair. Damage to the mammal heart—such as that caused by myocardial infarction—leads to scarring, resulting in cardiac dysfunction and heart failure. In contrast, the hearts of fish and urodele amphibians are capable of complete regeneration of cardiac tissue from multiple types of damage, with full restoration of functionality. In the last decades, research has revealed a wealth of information on how these animals are able to perform this remarkable feat, and non-mammalian models of heart repair have become a burgeoning new source of data on the morphological, cellular, and molecular processes necessary to heal cardiac damage. In this review we present the major findings from recent research on the underlying mechanisms of fish and amphibian heart regeneration. We also discuss the tools and techniques that have been developed to answer these important questions. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
1999 KiB  
Review
Roles of Antioxidative Enzymes in Wound Healing
by Toshihiro Kurahashi and Junichi Fujii
J. Dev. Biol. 2015, 3(2), 57-70; https://doi.org/10.3390/jdb3020057 - 27 Apr 2015
Cited by 176 | Viewed by 18357
Abstract
Since skin is the first barrier separating the body from the external environment, impaired wound healing can be life threatening to living organisms. Delayed healing processes are observed in animals under certain circumstances, such as advanced age, diabetes, and immunosuppression, but the underlying [...] Read more.
Since skin is the first barrier separating the body from the external environment, impaired wound healing can be life threatening to living organisms. Delayed healing processes are observed in animals under certain circumstances, such as advanced age, diabetes, and immunosuppression, but the underlying mechanisms of the abnormality remain elusive. Redox homeostasis is defined as the balance between the levels of reactive oxygen species (ROS) and antioxidants in which antioxidative enzymes play central roles in scavenging ROS. In addition to deleterious effects, ROS also exert beneficial functions on some cellular processes such as transducing phosphorylation signaling, but excessive antioxidants may impede the healing process. Hence, strict control over the amounts of antioxidants is desirable when applied for therapeutic purposes. Here we overview recent findings regarding the relationships between antioxidative enzymes and wound healing. Unveiling the role of antioxidative enzymes is expected to contribute to our understanding of the wound healing processes. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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2017 KiB  
Review
Inhibition of SERPINE1 Function Attenuates Wound Closure in Response to Tissue Injury: A Role for PAI-1 in Re-Epithelialization and Granulation Tissue Formation
by Tessa M. Simone and Paul J. Higgins
J. Dev. Biol. 2015, 3(1), 11-24; https://doi.org/10.3390/jdb3010011 - 2 Mar 2015
Cited by 13 | Viewed by 15303
Abstract
Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) is a prominent member of the serine protease inhibitor superfamily (SERPIN) and a causative factor of multi-organ fibrosis as well as a key regulator of the tissue repair program. PAI-1 attenuates pericellular proteolysis by inhibiting the catalytic activity [...] Read more.
Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) is a prominent member of the serine protease inhibitor superfamily (SERPIN) and a causative factor of multi-organ fibrosis as well as a key regulator of the tissue repair program. PAI-1 attenuates pericellular proteolysis by inhibiting the catalytic activity of both urokinase and tissue-type protease activators (uPA and tPA) effectively modulating, thereby, plasmin-mediated fibrinolysis and the overall pericellular proteolytic cascade. PAI-1 also impacts cellular responses to tissue injury and stress situations (growth, survival, migration) by titering the locale and temporal activation of multimeric cell-surface signaling complexes. This review will describe PAI-1 structure and function and detail the role of PAI-1 in the tissue repair program with an emphasis on cutaneous wound healing. Full article
(This article belongs to the Special Issue Wound Healing and Tissue Regeneration)
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