Growth Factors and Ocular Scarring

Growth factors play a part in every stage of the wound healing process that leads to scar tissue formation. Ocular scarring can cause decreased vision or blindness by virtue of the opaque nature of the new matrix that is deposited as scar tissue (as in the lens or cornea). In addition, the contractile nature of the ocular scar tissue is the most common cause of failed retinal attachment. Scar formation after glaucoma surgery can lead to surgery failure. Growth factors, particularly the transforming growth factor (TGF-βs), play a major role in scar tissue formation in the eye and induce the synthesis of growth factors that control cell migration, proliferation, enzyme production and matrix deposition. Neurotrophins are also neuroprotective and can delay ganglion cell death, thus delaying scar formation in the retina if retinal attachment is restored promptly. Growth factors can be seen as a major target for preventing ocular scarring in the future.

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Influence of Scar Tissue Formation on the Early Wound Healing Process of Palate Bones in Rats

Journal of Oral Biosciences ◽

10.1016/s1349-0079(05)80035-0 ◽

2005 ◽

Vol 47 (3) ◽

pp. 294-304

Author(s):

Hitoshi Kawanabe ◽

Shouichi Kinoshita ◽

Yuichiro Hata ◽

Hiroyuki Ishikawa ◽

Kazuhiko Okamura ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Scar Tissue ◽

Wound Healing Process ◽

Tissue Formation ◽

Early Wound ◽

Scar Tissue Formation

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Identifying wound infections for veterinary nurses

The Veterinary Nurse ◽

10.12968/vetn.2020.11.10.447 ◽

2020 ◽

Vol 11 (10) ◽

pp. 447-451

Author(s):

Amanda Curtis

Keyword(s):

Healing Process ◽

Scar Tissue ◽

Care Practice ◽

Wound Infections ◽

Tissue Formation ◽

Deep Tissue ◽

The Difference ◽

Bite Wounds ◽

Major Factors ◽

Scar Tissue Formation

Heavily contaminated wounds are a common occurrence in both referral and primary care practice, with traumatic and bite wounds being among the most typical aetiologies seen. Each type of wound can be affected by numerous factors that can inhibit the healing process, one of these major factors is infection. Wound infections and the formation of biofilms can present veterinary nurses with a variety of challenges, which is why it is important that we understand the difference between normal inflammatory signs and the signs of infection. The early identification of infection and biofilms within a wound can influence healing times, scar tissue formation and length of healing. This article aims to highlight the difference between inflammation and infection, the different levels of contamination within a wound, and ways to decipher between superficial and deep tissue infections.

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Tendon Cell Deletion of IKKβ/NF-κB Drives Functionally Deficient Tendon Healing and Altered Cell Survival Signaling In Vivo

10.1101/2020.03.03.974774 ◽

2020 ◽

Author(s):

Katherine T. Best ◽

Emma Knapp ◽

Constantinos Ketonis ◽

Jennifer H. Jonason ◽

Hani A. Awad ◽

...

Keyword(s):

Cell Survival ◽

Flexor Tendon ◽

Tendon Repair ◽

Tendon Healing ◽

Scar Tissue ◽

Cell Populations ◽

Tissue Formation ◽

Matrix Deposition ◽

Scar Tissue Formation

AbstractAcute tendon injuries are characterized by excessive matrix deposition that impedes regeneration and disrupts functional improvements. Inflammation is postulated to drive pathologic scar tissue formation, with nuclear factor kappa B (NF-κB) signaling emerging as a candidate pathway in this process. However, characterization of the spatial and temporal activation of canonical NF-κB signaling during tendon healing in vivo, including identification of the cell populations activating NF-κB, is currently unexplored. Therefore, we aimed to determine which cell populations activate canonical NF-κB signaling following flexor tendon repair with the goal of delineating cell-specific functions of NF-κB signaling during scar mediated tendon healing. Immunofluorescence revealed that both tendon cells and myofibroblasts exhibit prolonged activation of canonical NF-κB signaling into the remodeling phase of healing. Using cre-mediated knockout of the canonical NF-κB kinase (IKKβ), we discovered that suppression of canonical NF-κB signaling in Scleraxis-lineage cells increased myofibroblast content and scar tissue formation. Interestingly, Scleraxis-lineage specific knockout of IKKβ increased the incidence of apoptosis, suggesting that canonical NF-κB signaling may be mediating cell survival during tendon healing. These findings suggest indispensable roles for canonical NF-κB signaling during flexor tendon healing.One Sentence SummaryScleraxis-lineage specific knockdown of persistent canonical IKKβ/NF-κB drives scar formation and apoptotic signaling during flexor tendon healing.

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The Temporal Course of Adenovirus-Mediated Gene Transfer in the Rat Larynx

Otolaryngology ◽

10.1067/mhn.2002.122633 ◽

2002 ◽

Vol 126 (3) ◽

pp. 281-290

Author(s):

Jacobs Ian N. ◽

Tufano Ralph P. ◽

Walsh Danielle S. ◽

Crombleholme Timothy

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Gene Transfer ◽

Recombinant Adenovirus ◽

Marker Gene ◽

Care Facility ◽

Scar Tissue ◽

Complete Disappearance ◽

Tissue Formation ◽

Scar Tissue Formation

OBJECTIVE: Polypeptide growth factors have important influences on wound-healing and scar tissue formation. Specific growth factors or their inhibitors may potentially decrease scar tissue formation and prevent subglottic stenosis. Gene transfer using recombinant adenovirus may be an ideal method to mediate endogenous production of growth factors to inhibit fibrosis. STUDY DESIGN: The study incorporated adenovirus-mediated transduction of normal and stenotic rat larynges and histologic analysis of the sequential expression of a β-galactosidase marker gene over time. SETTING: The study was conducted at the animal care facility of an academic children's hospital. RESULTS: We report successful transduction in normal and injured rat larynx with peak expression of β-galactosidase at 2 days after transduction and almost complete disappearance by 7 days. There appeared to be an early inflammatory response to the viral injection, but at 7 and 14 days after injection (transduction) the uninjured rat larynges resumed a normal histologic appearance. All distant sites stained negative for β-galactosidase. CONCLUSION: Recombinant adenovirus-mediated gene transfer is feasible in the rat larynx with transient duration and limited toxicity. SIGNIFICANCE: Adenovirus-mediated gene transfer has the potential to deliver growth factors that modulate wound healing and inflammation in the larynx by inhibiting fibrosis.

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Study of Wound Healing in Rats Treated with Topical and Injected Mitomycin C

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940811701015 ◽

2008 ◽

Vol 117 (10) ◽

pp. 786-790 ◽

Cited By ~ 5

Author(s):

Fernando de Andrade Quintanilha Ribeiro ◽

Lusiele Guaraldo ◽

Janaina de Pádua Borges ◽

Maria Regina Vianna ◽

Claudia A. Eckley

Keyword(s):

Mitomycin C ◽

Topical Treatment ◽

Healing Process ◽

Microscopic Analysis ◽

Scar Tissue ◽

Control Group ◽

Tissue Formation ◽

Chemotherapeutic Drug ◽

Surgical Wounds ◽

Scar Tissue Formation

Objectives: Mitomycin C, a widely used chemotherapeutic drug, has been proposed as a potential adjuvant for the control of scar tissue in surgical wounds because of its capacity to inhibit fibroblast proliferation. The current study used a combination of topical and injected mitomycin C to slow the healing process of surgical wounds in rats. Methods: An experimental model of surgical wounding at the dorsum of rats was used. A total of 43 animals were subdivided into 3 groups: Control, topical mitomycin C, and a combination of topical treatment and intradermal injections of the drug at 30 and 60 days after the initial topical treatment. After 3 months, the animals were painlessly sacrificed and the surgical scars were removed for microscopic analysis. Results: The group that received only topical mitomycin C presented milder inflammatory signs and consequently had a less intense healing process than the control group. The group treated with a combination of both topical and injected mitomycin C presented results comparable to those of the control group. Conclusions: The toxic characteristics of mitomycin C were most likely responsible for the greater tissue damage that occurred when it was used in the injected form, causing increased scar tissue formation. Mitomycin C slows the healing process of surgical wounds when used topically, but causes enhanced scar tissue formation when injected.

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Knockdown of lysyl oxidase like 1 inhibits the proliferation and pro-fibrotic effects of Transforming growth factor-β1-induced hypertrophic scar fibroblasts

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0242 ◽

2021 ◽

Author(s):

Mengxia Ying ◽

Yan Chen ◽

Bo Yuan

Keyword(s):

Cell Cycle ◽

Western Blot ◽

Wound Repair ◽

Transforming Growth Factor ◽

Lysyl Oxidase ◽

Healing Process ◽

Cell Cycle Distribution ◽

Wound Healing Process ◽

Matrix Deposition ◽

Tgf Β1

Background: The excessive healing response during wound repair can result in hypertrophic scars (HS). Lysyl oxidase like 1 (LOXL1) has been reported to be associated with fibrosis via targeting TGF-β1 signaling. This study aimed to investigate the effect of LOXL1 on HS formation. Methods: The expression of LOXL1 in HS tissues and TGF-β1-induced HSFs was detected via RT-qPCR and western blot. LOXL1 was silenced in HSFs using transfection with short hairpin RNA (shRNA), then wound healing process including cell proliferation, cell cycle distribution, migration and extracellular matrix deposition along with Smad expression were measured by CCK-8, EdU staining, flow cytometry, transwell, immunofluorescence and western blot assays. Results: LOXL1 was up-regulated in HS tissues and TGF-β1-induced HSFs. Knockdown of LOXL1 inhibited proliferation and migration, but promoted cell cycle G0/G1 phase arrest in TGF-β1-induced HSFs. The increased expression of cyclin D1, CDK4, MMP2, MMP9, COL1A1, COL1A2, fibronectin, COL3A1, α-SMA, but decreased expression of p27, and the phosphorylation of Smad2 and Smad3 caused by TGF-β1 were also blocked by LOXL1 silence. Conclusions: Silence of LOXL1 could effectively inhibit TGF-β1-induced proliferation, migration and ECM deposition in HSFs via inactivating Smad pathway. Targeting LOXL1 may have future therapeutic implications for HS treatment.

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Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting

Current Pharmaceutical Design ◽

10.2174/1381612826666200612164511 ◽

2020 ◽

Vol 26 (36) ◽

pp. 4551-4568

Author(s):

Mohammad Kashif Iqubal ◽

Sadaf Saleem ◽

Ashif Iqubal ◽

Aiswarya Chaudhuri ◽

Faheem Hyder Pottoo ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Photodynamic Therapy ◽

Growth Factors ◽

Combination Therapy ◽

Healing Process ◽

Wound Healing Process ◽

Wound Site ◽

Synthetic Drugs ◽

Treatment Paradigm

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

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Experimental Methods to Simulate and Evaluate Postsurgical Peripheral Nerve Scarring

Journal of Clinical Medicine ◽

10.3390/jcm10081613 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1613

Author(s):

Alessandro Crosio ◽

Giulia Ronchi ◽

Benedetta Elena Fornasari ◽

Simonetta Odella ◽

Stefania Raimondo ◽

...

Keyword(s):

Peripheral Nerve ◽

Peripheral Nerves ◽

Experimental Methods ◽

Scar Tissue ◽

Experimental Models ◽

Tissue Formation ◽

Surgical Interventions ◽

Pubmed Database ◽

Different Types ◽

Scar Tissue Formation

As a consequence of trauma or surgical interventions on peripheral nerves, scar tissue can form, interfering with the capacity of the nerve to regenerate properly. Scar tissue may also lead to traction neuropathies, with functional dysfunction and pain for the patient. The search for effective antiadhesion products to prevent scar tissue formation has, therefore, become an important clinical challenge. In this review, we perform extensive research on the PubMed database, retrieving experimental papers on the prevention of peripheral nerve scarring. Different parameters have been considered and discussed, including the animal and nerve models used and the experimental methods employed to simulate and evaluate scar formation. An overview of the different types of antiadhesion devices and strategies investigated in experimental models is also provided. To successfully evaluate the efficacy of new antiscarring agents, it is necessary to have reliable animal models mimicking the complications of peripheral nerve scarring and also standard and quantitative parameters to evaluate perineural scars. So far, there are no standardized methods used in experimental research, and it is, therefore, difficult to compare the results of the different antiadhesion devices.

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Multi-Functional Core-Shell Nanofibers for Wound Healing

Nanomaterials ◽

10.3390/nano11061546 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1546

Author(s):

Zhen Li ◽

Shunqi Mei ◽

Yajie Dong ◽

Fenghua She ◽

Puwang Li ◽

...

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Drug Release ◽

Release Rate ◽

Healing Process ◽

Wound Healing Process ◽

Core Shell ◽

High Production Rate ◽

Centrifugal Spinning ◽

Multiple Drugs

Core-shell nanofibers have great potential for bio-medical applications such as wound healing dressings where multiple drugs and growth factors are expected to be delivered at different healing phases. Compared to monoaxial nanofibers, core-shell nanofibers can control the drug release profile easier, providing sustainable and effective drugs and growth factors for wound healing. However, it is challenging to produce core-shell structured nanofibers with a high production rate at low energy consumption. Co-axial centrifugal spinning is an alternative method to address the above limitations to produce core-shell nanofibers effectively. In this study, a co-axial centrifugal spinning device was designed and assembled to produce core-shell nanofibers for controlling the release rate of ibuprofen and hEGF in inflammation and proliferation phases during the wound healing process. Core-shell structured nanofibers were confirmed by TEM. This work demonstrated that the co-axial centrifugal spinning is a high productivity process that can produce materials with a 3D environment mimicking natural tissue scaffold, and the specific drug can be loaded into different layers to control the drug release rate to improve the drug efficiency and promote wound healing.

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