Forceful closure: cytoskeletal networks in embryonic wound repair

Embryonic tissues heal wounds rapidly and without scarring, in a process conserved across species and driven by collective cell movements. The mechanisms of coordinated cell movement during embryonic wound closure also drive tissue development and cancer metastasis; therefore, embryonic wound repair has received considerable attention as a model of collective cell migration. During wound closure, a supracellular actomyosin cable at the wound edge coordinates cells, while actin-based protrusions contribute to cell crawling and seamless wound healing. Other cytoskeletal networks are reorganized during wound repair: microtubules extend into protrusions and along cell–cell boundaries as cells stretch into damaged regions, septins accumulate at the wound margin, and intermediate filaments become polarized in the cells adjacent to the wound. Thus, diverse cytoskeletal networks work in concert to maintain tissue structure, while also driving and organizing cell movements to promote rapid repair. Understanding the signals that coordinate the dynamics of different cytoskeletal networks, and how adhesions between cells or with the extracellular matrix integrate forces across cells, will be important to elucidate the mechanisms of efficient embryonic wound healing and may have far-reaching implications for developmental and cancer cell biology.

Download Full-text

Management of Acute Wounds

10.2310/anes.2022 ◽

2019 ◽

Author(s):

Lee D. Faucher ◽

Angela L. Gibson

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Wound Closure ◽

Wound Care ◽

Connective Tissue Diseases ◽

Skin Grafting ◽

Adjunctive Treatment ◽

Local Trauma ◽

Life Threatening ◽

Acute Wound

Acute wounds are the result of local trauma and may be associated with severe life-threatening injuries. All patients with acute wounds should be assessed for comorbidities such as malnutrition, diabetes, peripheral vascular disease, neuropathy, obesity, immune deficiency, autoimmune disorders, connective tissue diseases, coagulopathy, hepatic dysfunction, malignancy, smoking practices, medication use that could interfere with healing, and allergies. The authors address the key considerations in management of the acute wound, including anesthesia, location of wound repair (e.g. operating room or emergency department), hemostasis, irrigation, débridement, closure materials, timing and methods of closure, adjunctive treatment (e.g. tetanus and rabies prophylaxis, antibiotics, and nutritional supplementation), appropriate closure methods for specific wound types, dressings, postoperative wound care, and potential disturbances of wound healing. This review contains 11 figures, 31 tables, and 92 references. Keywords: wound, wound infection, burns, suture, staple, wound closure, wound healing, dehiscence, skin grafting

Download Full-text

Actin and myosin dynamics are independent during Drosophila embryonic wound repair

Molecular Biology of the Cell ◽

10.1091/mbc.e18-11-0703 ◽

2019 ◽

Vol 30 (23) ◽

pp. 2901-2912

Author(s):

Anna B. Kobb ◽

Katheryn E. Rothenberg ◽

Rodrigo Fernandez-Gonzalez

Keyword(s):

Wound Repair ◽

Wound Closure ◽

Molecular Motor ◽

Wound Edge ◽

Cell Movements ◽

Nonmuscle Myosin Ii ◽

Wound Margin ◽

Wound Healing Response ◽

Disease Cell ◽

Drosophila Embryos

Collective cell movements play a central role in embryonic development, tissue repair, and metastatic disease. Cell movements are often coordinated by supracellular networks formed by the cytoskeletal protein actin and the molecular motor nonmuscle myosin II. During wound closure in the embryonic epidermis, the cells around the wound migrate collectively into the damaged region. In Drosophila embryos, mechanical tension stabilizes myosin at the wound edge, facilitating the assembly of a supracellular myosin cable around the wound that coordinates cell migration. Here, we show that actin is also stabilized at the wound edge. However, loss of tension or myosin activity does not affect the dynamics of actin at the wound margin. Conversely, pharmacological stabilization of actin does not affect myosin levels or dynamics around the wound. Together, our data suggest that actin and myosin are independently regulated during embryonic wound closure, thus conferring robustness to the embryonic wound healing response.

Download Full-text

Eradication of Mature Bacterial Biofilms with Concurrent Improvement in Chronic Wound Healing Using Silver Nanoparticle Hydrogel Treatment

Biomedicines ◽

10.3390/biomedicines9091182 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1182

Author(s):

Hanif Haidari ◽

Richard Bright ◽

Sanjay Garg ◽

Krasimir Vasilev ◽

Allison J. Cowin ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Wound Closure ◽

In Vivo Studies ◽

Release Mechanism ◽

Impaired Wound Healing ◽

Biofilm Model ◽

Infected Wounds ◽

Delivery Platform

Biofilm-associated infections are a major cause of impaired wound healing. Despite the broad spectrum of anti-bacterial benefits provided by silver nanoparticles (AgNPs), these materials still cause controversy due to cytotoxicity and a lack of efficacy against mature biofilms. Herein, highly potent ultrasmall AgNPs were combined with a biocompatible hydrogel with integrated synergistic functionalities to facilitate elimination of clinically relevant mature biofilms in-vivo combined with improved wound healing capacity. The delivery platform showed a superior release mechanism, reflected by high biocompatibility, hemocompatibility, and extended antibacterial efficacy. In vivo studies using the S. aureus wound biofilm model showed that the AgNP hydrogel (200 µg/g) was highly effective in eliminating biofilm infection and promoting wound repair compared to the controls, including silver sulfadiazine (Ag SD). Treatment of infected wounds with the AgNP hydrogel resulted in faster wound closure (46% closure compared to 20% for Ag SD) and accelerated wound re-epithelization (60% for AgNP), as well as improved early collagen deposition. The AgNP hydrogel did not show any toxicity to tissue and/or organs. These findings suggest that the developed AgNP hydrogel has the potential to be a safe wound treatment capable of eliminating infection and providing a safe yet effective strategy for the treatment of infected wounds.

Download Full-text

Optimal Support of Wound Healing: New Insights

Dermatology ◽

10.1159/000505291 ◽

2020 ◽

Vol 236 (6) ◽

pp. 593-600 ◽

Cited By ~ 7

Author(s):

Jens Malte Baron ◽

Martin Glatz ◽

Ehrhardt Proksch

Keyword(s):

Wound Healing ◽

Best Practices ◽

Wound Closure ◽

Wound Care ◽

Clinical Approach ◽

Visual Appearance ◽

Rapid Repair ◽

Wound Recovery ◽

Scar Management ◽

Three Phases

Background: The ultimate goal of wound healing following minor injury is to form a tissue regenerate that has functionality and visual appearance as close to the original skin as possible. The body’s physiological response to any wound is traditionally characterised by three distinct steps: inflammation, proliferation and remodelling. Summary: New insights suggest that the three phases overlap (and even occur in parallel) in both time and space in the wound, necessitating a clinical approach that targets each stage simultaneously to ensure rapid repair and wound closure without further complications. Ingredients that exhibit activity across each of the three phases, such as dexpanthenol, are of value in the context of minor wound care and scar management. Key Messages: In addition to treatment and ingredient selection, it is also important to consider broader clinical best practices and self-care options that can be used to optimise the management of minor wounds. An individualised approach that can account for a patient’s unique requirements and preferences is critical in achieving effective wound recovery.

Download Full-text

A central role for vimentin in regulating repair function during healing of the lens epithelium

Molecular Biology of the Cell ◽

10.1091/mbc.e12-12-0900 ◽

2014 ◽

Vol 25 (6) ◽

pp. 776-790 ◽

Cited By ~ 64

Author(s):

A. S. Menko ◽

B. M. Bleaken ◽

A. A. Libowitz ◽

L. Zhang ◽

M. A. Stepp ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Wound Closure ◽

Cell Function ◽

Healing Process ◽

Critical Role ◽

Focal Adhesions ◽

Lens Epithelium ◽

Wound Healing Process ◽

Vimentin Filaments

Mock cataract surgery provides a unique ex vivo model for studying wound repair in a clinically relevant setting. Here wound healing involves a classical collective migration of the lens epithelium, directed at the leading edge by an innate mesenchymal subpopulation of vimentin-rich repair cells. We report that vimentin is essential to the function of repair cells as the directors of the wound-healing process. Vimentin and not actin filaments are the predominant cytoskeletal elements in the lamellipodial extensions of the repair cells at the wound edge. These vimentin filaments link to paxillin-containing focal adhesions at the lamellipodial tips. Microtubules are involved in the extension of vimentin filaments in repair cells, the elaboration of vimentin-rich protrusions, and wound closure. The requirement for vimentin in repair cell function is revealed by both small interfering RNA vimentin knockdown and exposure to the vimentin-targeted drug withaferin A. Perturbation of vimentin impairs repair cell function and wound closure. Coimmunoprecipitation analysis reveals for the first time that myosin IIB is associated with vimentin, linking vimentin function in cell migration to myosin II motor proteins. These studies reveal a critical role for vimentin in repair cell function in regulating the collective movement of the epithelium in response to wounding.

Download Full-text

Adenosine A2A receptors promote adenosine-stimulated wound healing in bronchial epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00373.2005 ◽

2006 ◽

Vol 290 (5) ◽

pp. L849-L855 ◽

Cited By ~ 32

Author(s):

D. S. Allen-Gipson ◽

J. Wong ◽

J. R. Spurzem ◽

J. H. Sisson ◽

T. A. Wyatt

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Adenosine Receptor ◽

Wound Repair ◽

Wound Closure ◽

Bronchial Epithelial Cells ◽

Dependent Manner ◽

Closure Rate ◽

Concentration Dependent Manner ◽

Bronchial Epithelial

Adenosine produces a wide variety of physiological effects through the activation of specific adenosine receptors (A1, A2A, A2B, A3). Adenosine, acting particularly at the A2A adenosine receptor (A2AAR), is a potent endogenous anti-inflammatory agent and sensor of inflammatory tissue damage. The complete healing of wounds is the final step in a highly regulated response to injury. Recent studies on epidermal wounds have identified the A2AAR as the main adenosine receptor responsible for altering the kinetics of wound closure. We hypothesized that A2AAR promotes wound healing in bronchial epithelial cells (BECs). To test this hypothesis, the human BEC line BEAS-2B and bovine BECs (BBECs) were used. Real-time RT-PCR of RNA from unstimulated BEAS-2B cells revealed transcriptional expression of A1, A2A, A2B and A3 receptors. Western blot analysis of lysates from BEAS-2B cells and BBECs detected a single band at 44.7 kDa in both the BECs, indicating the presence of A2AAR. In a wound healing model, we found that adenosine stimulated wound repair in cultured BBECs in a concentration-dependent manner, with an optimal closure rate observed between 4 and 6 h. Similarly, the A2AAR agonist 5′-( N-cyclopropyl)carboxamidoadenosine (CPCA) augmented wound closure, with a maximal closure rate occurring between 4 and 6 h. Inhibition of A2AAR with ZM-241385, a known A2AAR antagonist, impeded wound healing. In addition, ZM-241385 also attenuated adenosine-mediated wound repair. Kinase studies revealed that adenosine-stimulated airway repair activates PKA by ligating A2AAR. Collectively, the data suggest that the A2AAR is involved in BEC adenosine-stimulated wound healing and may prove useful in understanding purinergic-mediated actions on airway epithelial repair.

Download Full-text

Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

Molecular Biology of the Cell ◽

10.1091/mbc.e17-05-0305 ◽

2017 ◽

Vol 28 (19) ◽

pp. 2579-2588 ◽

Cited By ~ 25

Author(s):

Puja Sharma ◽

Colin Ng ◽

Aniket Jana ◽

Abinash Padhi ◽

Paige Szymanski ◽

...

Keyword(s):

Cell Migration ◽

Cell Biology ◽

Cancer Metastasis ◽

Rubber Band ◽

Cell Junctions ◽

Collective Cell Migration ◽

Cell Sheets ◽

Cell Monolayers ◽

Fiber Arrays

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.

Download Full-text

Collective Cell Migration: A Mechanistic Perspective

Physiology ◽

10.1152/physiol.00033.2013 ◽

2013 ◽

Vol 28 (6) ◽

pp. 370-379 ◽

Cited By ~ 61

Author(s):

Sri Ram Krishna Vedula ◽

Andrea Ravasio ◽

Chwee Teck Lim ◽

Benoit Ladoux

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Social Behavior ◽

Cancer Metastasis ◽

Collective Cell Migration ◽

Biological Processes ◽

The Social ◽

Holistic Understanding ◽

Broad Overview

Collective cell migration is fundamental to gaining insights into various important biological processes such as wound healing and cancer metastasis. In particular, recent in vitro studies and in silico simulations suggest that mechanics can explain the social behavior of multicellular clusters to a large extent with minimal knowledge of various cellular signaling pathways. These results suggest that a mechanistic perspective is necessary for a comprehensive and holistic understanding of collective cell migration, and this review aims to provide a broad overview of such a perspective.

Download Full-text

Principles of wound healing and growth factor considerations

Journal of the American Podiatric Medical Association ◽

10.7547/87507315-83-4-223 ◽

1993 ◽

Vol 83 (4) ◽

pp. 223-227 ◽

Cited By ~ 7

Author(s):

SJ Skokan ◽

RH Davis

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Growth Factor ◽

Wound Repair ◽

Wound Closure ◽

Cellular Proliferation ◽

Positive Influence ◽

Surgical Wounds ◽

And Migration ◽

Proliferation And Migration

This review examines some of the important principles in wound repair and significant considerations for the use of growth factors. Moisture provides a positive influence on the mechanical and hormonal aspects of wounds. Atraumatic closure of surgical wounds and postoperative care and the types of wound closure are discussed. Cellular proliferation and migration in wounds are central features regarding growth factors.

Download Full-text

Abnormal Angiogenesis, Neurogenesis and Lymphangiogenesis in the Skin Underlies Delayed Wound Healing in the Sickle Mouse: Acceleration of Healing by Topical Opioids.

Blood ◽

10.1182/blood.v106.11.3177.3177 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3177-3177 ◽

Cited By ~ 2

Author(s):

Kalpna Gupta ◽

Tasneem Poonawala ◽

Brett K. Levay-Young ◽

Marna E. Ericson ◽

Niroop S. Ammbashankar ◽

...

Keyword(s):

Wound Healing ◽

Blood Vessels ◽

Laser Scanning ◽

Wound Repair ◽

Lymphatic Vessel ◽

Wound Closure ◽

Lymphatic Vessels ◽

Hair Follicles ◽

Sensory Nerves ◽

Leg Ulcers

Abstract Chronic non-healing and painful leg ulcers are a serious manifestation of sickle cell disease (SCD). We hypothesized that structurally and functionally aberrant interdependent triad of angiogenesis, neurogenesis and lymphangiogenesis leads to localized ischemic insult, pain and edema, respectively, resulting in non-healing, painful and ulcerative wounds in SCD. We examined the dorsal skin of sickle mice with different severity (mild, NY1DD, medium, hBERK and severe, BERK) for blood vessels, sensory nerves and lymphatic vessels, by immunostaining 100 micron thick cryosections with endothelial specific anti-CD31, PGP9.5 and calcitonin gene related peptide (CGRP) and anti-lymphatic vessel endothelium marker LYVE-1, respectively. Z-series images were acquired using using laser scanning confocal microscopy. We observed a drastic difference in the structure, presentation and localization of all three processes in sickle mice as compared to their controls, which increased with the severity of the model. We found that, [i] epidermal thickening in BERK is 1/2 vs HbABERK (control expressing normal human Hb), [ii] majority of blood vessels localized in the sub-epidermal region in BERK vs dermal tissue in controls, [iii] microvasculature shows disorganization,tortuous, stringy and collapsed vessels in sickle, [iv] open lymphatic vessels arranged in parallel union with hair follicles in controls collapsed to 50 and 90% in diameter in mild and severe sickle models, respectively, while they moved by 90° becoming perpendicular to hair follicles in the severe sickle; [v] Peptidergic-immunoreactive nerve fibres increased with the severity of sickle state in the epidermis; and [vi] CGRP, a mediator in pain transmission is upregulated 2–5 times in sickle vs controls. These data suggest that aberrant, non-functional blood vessels lead to the development of localized hypoxia and ischemia resulting in tissue damage and compression of lymphatics which in turn increase edema and ulceration. Upregulated CGRP on peripheral nerves is suggestive of severe pain associated with sickle ulcers. Opioids interact with endothelium as well as nerves and promote angiogenesis and analgesia, respectively. Therefore, we examined the effect of topically applied opioids on healing of ischemic wounds in hBERK. In PBS treated HbABERK control, wound healing was 62% vs 42% in sickle on day 12 (p< 0.02). Complete wound closure was observed on day 19 in HbABERK, whereas, complete healing did not occur in sickle mice until 28 days. Topical application of morphine resulted in complete closure of wounds by days 14 and 23 in HbABERK and sickle mice, respectively. Similarly, hydromorphone stimulated complete wound closure as compared to 85% closure with PBS by day 23 in sickle (p<0.03). Blood and lymphatic vessel lengths were 20–35% higher in morphine or hydromorphone vs PBS-cream treated sickle wounds on days 13 and 28, respectively (p<0.05 PBS-Cream vs others on days 13 and 28). Thus wound repair is delayed in SCD due to aberrant vasculature and lymphatics and opioids stimulate normal angiogenesis and lymphangiogenesis which promote wound healing. We speculate that topical opioids may accelerate wound healing in painful non-healing leg ulcers in SCD.

Download Full-text