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The British Journal of Dermatology Aug 2015A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal... (Review)
Review
A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.
Topics: Acute Disease; Animals; Chronic Disease; Cicatrix; Disease Models, Animal; Drosophila; Granulation Tissue; Humans; Immunity, Cellular; Inflammation; Neovascularization, Physiologic; Nerve Regeneration; Re-Epithelialization; Wound Healing; Wound Infection; Zebrafish
PubMed: 26175283
DOI: 10.1111/bjd.13954 -
The Journal of Investigative Dermatology May 2007Cutaneous tissue repair aims at restoring the barrier function of the skin. To achieve this, defects need to be replaced by granulation tissue to form new connective... (Review)
Review
Cutaneous tissue repair aims at restoring the barrier function of the skin. To achieve this, defects need to be replaced by granulation tissue to form new connective tissue, and epithelial wound closure is required to restore the physical barrier. Different wound-healing phases are recognized, starting with an inflammation-dominated early phase giving way to granulation tissue build-up and scar remodeling after epithelial wound closure has been achieved. In the granulation tissue, mesenchymal cells are maximally activated, cells proliferate, and synthesize huge amounts of extracellular matrix. Epithelial cells also proliferate and migrate over the provisional matrix of the underlying granulation tissue, eventually closing the defect. This review focuses on the role of keratinocyte-fibroblast interactions in the wound-healing process. There is ample evidence that keratinocytes stimulate fibroblasts to synthesize growth factors, which in turn will stimulate keratinocyte proliferation in a double paracrine manner. Moreover, fibroblasts can acquire a myofibroblast phenotype under the control of keratinocytes. This depends on a finely tuned balance between a proinflammatory or a transforming growth factor (TGF)-beta-dominated environment. As the phenotype of fibroblasts from different tissues or body sites becomes better defined, we may understand their individual contribution in wound healing in more detail and possibly explain different clinical outcomes.
Topics: Animals; Cell Communication; Epithelial Cells; Extracellular Matrix; Fibroblasts; Granulation Tissue; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Wound Healing
PubMed: 17435785
DOI: 10.1038/sj.jid.5700786 -
Journal of Periodontal Research Aug 2018Determine the presence of mesenchymal stem cells (MSCs) in healthy periodontal tissue and periodontal granulation tissue (GT) and explore associations between...
BACKGROUND AND OBJECTIVES
Determine the presence of mesenchymal stem cells (MSCs) in healthy periodontal tissue and periodontal granulation tissue (GT) and explore associations between immuno-regulatory molecules and selected subgingival microorganisms.
MATERIAL AND METHODS
Mesenchymal stem cells were isolated, propagated and characterised by flow cytometry from a region of healthy gingival tissue and inflamed GT of 10 systemically healthy non-smokers with chronic periodontitis. Tissue levels of immunoregulatory molecules were determined by qPCR and Gingival Crevicular Fluid (GCF) levels by ELISA. Subgingival plaque levels of periodontal pathogens were determined by qPCR RESULTS: Cells with MSC-properties were isolated from both inflamed GT and healthy gingival (G) tissue. A pro-inflammatory process predominated in GT which was partly reflected in GCF and putative periodontal pathogens were higher at diseased sites. However, there was no significant difference in surface levels of mesenchymal (CD90, CD73, CD146, CD271, STRO-1), endothelial (CD105, CD106), hematopoietic (CD34, CD45) and embryonic (SSEA-4) stem cell markers between MSCs isolated from GT and G tissue.
CONCLUSION
Periodontal lesions, albeit inflamed, retain healing potential as inferred by the presence of MSC-like cells with similar immunophenotypic characteristics to those found in healthy periodontal tissue. Therefore, there might be merits for healing in preserving sufficient GT in-situ during periodontal surgery.
Topics: Biomarkers; Biopsy; Chronic Periodontitis; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Gingival Crevicular Fluid; Granulation Tissue; Humans; Immunophenotyping; Male; Mesenchymal Stem Cells; Middle Aged; Periodontium; Real-Time Polymerase Chain Reaction
PubMed: 29687448
DOI: 10.1111/jre.12551 -
Stem Cell Research & Therapy Apr 2015Skin as the largest and easily accessible organ of the body represents an abundant source of adult stem cells. Among them, dermal stem cells hold great promise in tissue...
INTRODUCTION
Skin as the largest and easily accessible organ of the body represents an abundant source of adult stem cells. Among them, dermal stem cells hold great promise in tissue repair and the skin granulation tissue has been recently proposed as a promising source of dermal stem cells, but their biological characteristics have not been well investigated.
METHODS
The 5-bromo-2'-deoxyuridine (BrdU) lineage tracing approach was employed to chase dermal stem cells in vivo. Granulation tissue derived cells (GTCs) were isolated and their in vitro proliferation, self-renewing, migration, and multi-differentiation capabilities were assessed. Combined radiation and skin wound model was used to investigate the therapeutic effects of GTCs. MicroRNA-21 (miR-21) antagomir was used to antagonize miR-21 expression. Reactive oxygen species (ROS) were scavenged by N-acetyl cysteine (NAC).
RESULTS
The quiescent dermal stem/progenitor cells were activated to proliferate upon injury and enriched in granulation tissues. GTCs exhibited enhanced proliferation, colony formation and multi-differentiation capacities. Topical transplantation of GTCs into the combined radiation and skin wound mice accelerated wound healing and reduced tissue fibrosis. Blockade of the miR-21 expression in GTCs inhibited cell migration and differentiation, but promoted cell proliferation and self-renewing at least partially via a ROS dependent pathway.
CONCLUSIONS
The granulation tissue may represent an alternative adult stem cell source in tissue replacement therapy and miR-21 mediated ROS generation negatively regulates the stemness-related properties of granulation tissue derived cells.
Topics: Acetylcysteine; Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Dermis; Disease Models, Animal; Gene Knock-In Techniques; Granulation Tissue; Mice; Mice, Inbred C57BL; MicroRNAs; Oligonucleotides, Antisense; Reactive Oxygen Species; Skin Diseases; Stem Cell Transplantation; Stem Cells; Wound Healing
PubMed: 25925316
DOI: 10.1186/s13287-015-0070-9 -
Wounds : a Compendium of Clinical... Aug 2016Oxygen must be tightly governed in all phases of wound healing to produce viable granulation tissue. This idea of tight regulation has yet to be disputed; however, the... (Review)
Review
Oxygen must be tightly governed in all phases of wound healing to produce viable granulation tissue. This idea of tight regulation has yet to be disputed; however, the role of oxygen at the cellular and molecular levels still is not fully understood as it pertains to its place in healing wounds. In an attempt to better understand the dynamics of oxygen on living tissue and its potential role as a therapy in wound healing, a substantial literature review of the role of oxygen in wound healing was performed and the following key points were extrapolated: 1) During energy metabolism, oxygen is needed for mitochondrial cytochrome oxidase as it produces high-energy phosphates that are needed for many cellular functions, 2) oxygen is also involved in the hydroxylation of proline and lysine into procollagen, which leads to collagen maturation, 3) in angiogenesis, hypoxia is required to start the process of wound healing, but it has been shown that if oxygen is administered it can accelerate and sustain vessel growth, 4) the antimicrobial action of oxygen occurs when nicotinamide adenine dinucleotide phosphate (NADPH)-linked oxygenase acts as a catalyst for the production of reactive oxygen species (ROS), a superoxide ion which kills bacteria, and 5) the level of evidence is moderate for the use of hyperbaric oxygen therapy (HBOT) for diabetic foot ulcers, crush injuries, and soft-tissue infections. The authors hypothesized that HBOT would be beneficial to arterial insufficiency wounds and other ailments, but at this time further study is needed before HBOT would be indicated.
Topics: Chronic Disease; Evidence-Based Medicine; Granulation Tissue; Humans; Hyperbaric Oxygenation; Wound Healing; Wounds and Injuries
PubMed: 27560469
DOI: No ID Found -
Biomedical Papers of the Medical... Jun 2021Granulation tissue (GT) and specialized pro‑resolving mediators such as lipoxins and resolvins are key elements in the successful resolution of periodontitis....
AIMS
Granulation tissue (GT) and specialized pro‑resolving mediators such as lipoxins and resolvins are key elements in the successful resolution of periodontitis. Aspirin‑triggered lipoxins and resolvins are even more powerful than their natural analogues. Their biosynthesis can be accelerated by omega-3 fatty acids. The aim of this study was to evaluate the use of GT enriched by aspirin and omega-3 fatty acids during the surgical treatment of periodontitis in an experimental animal model (rabbit).
METHODS
In each of 24 rabbits, two experimental periodontal defects were created. In total, 47 defects were treated with open-flap debridement and one of three procedures: (1) GT extracted and soaked with aspirin and omega-3 fatty acids (ASA+OMEGA3 group); (2) GT soaked with saline (PLACEBO group); or (3) GT left untreated (CONTROL group). Then, the GT was replaced in situ. Primary evaluated criteria were the probing pocket depth (PPD) and the clinical attachment level (CAL). Necropsies were harvested 2, 6, and 12 weeks after surgery. The samples were used for histological and molecular biological assessment.
RESULTS
A trend of greater PPD and CAL in the ASA+OMEGA3 group was observed at 6 weeks. However, there was no significant difference between them. During the observation period, tissue levels of FGF-7, IL-1β and TIMP-1 showed a statistically significant decrease (P<0.05). For the other variables, the ASA+OMEGA3 group was comparable with the PLACEBO and CONTROL groups.
CONCLUSION
This experiment did not demonstrate the superiority of the proposed approach. However, the enriched granulation tissue did not impair healing outcomes.
Topics: Animals; Aspirin; Fatty Acids, Omega-3; Granulation Tissue; Lipoxins; Periodontitis; Rabbits
PubMed: 32091012
DOI: 10.5507/bp.2020.003 -
European Respiratory Review : An... Sep 2021Increasing numbers of endoscopically implantable devices are implanted in the airways, such as airway stents, one-way valves and coils, to treat both malignant and... (Review)
Review
Increasing numbers of endoscopically implantable devices are implanted in the airways, such as airway stents, one-way valves and coils, to treat both malignant and benign diseases. They significantly improve patient outcomes, but their long-term effectiveness and sustainability is hampered by the reaction of the formation of granulation tissue. Factors including procedural-related tissue injury; micro-organism presence; device-related factors, such as the material, design and sizing in relation to the airway; and patient-related factors, including genetic susceptibility, comorbidities and medication use, might all effect the severity of the tissue response and the subsequent degree of granulation tissue formation. However, research into the underlying mechanism and risk factors is scarce and therefore our knowledge is limited. Joint efforts from the scientific community, both pre-clinical and clinical, are needed to gain a deeper understanding and eventually improve the long-term treatment effectiveness of lung-implantable devices.
Topics: Granulation Tissue; Humans; Lung; Stents
PubMed: 34348981
DOI: 10.1183/16000617.0066-2021 -
Frontiers in Bioscience (Landmark... Jan 2009Macrophage recruitment and proliferation of both small vessels (endothelium and pericytes) and fibroblast-myofibroblasts are the fundamental and provisional cellular... (Review)
Review
Macrophage recruitment and proliferation of both small vessels (endothelium and pericytes) and fibroblast-myofibroblasts are the fundamental and provisional cellular findings in repair through granulation tissue (RTGT).Endothelium and pericytes of preexisting microvasculature may act as progenitor cells of new endothelial cells and new pericyte-fibroblast-myofibroblasts, respectively.Likewise, fibroblasts may be progenitors of themselves, and of myofibroblasts and pericytes. Moreover, all these cells may originate from circulating progenitor cells or other progenitor cells..According to this extensive cellular plasticity, this work reviews the adult stem cells (ASC) and transit- amplifying cells (TAC) related to the principal cellular components of RTGT.Moreover, we hypothesize that the perivascular region, with a heterogeneous pericyte-like cellular population, including pericytes, perivascular fibroblasts and homing cells from the bone marrow (fibrocytes and bone marrow mesenchymal cells), is the niche of progenitor cells in RTGT and the substrate of regulatory mechanisms (perivascular niche hypothesis).We also highlight RTGT as a "paracrine transitional organ" during involutive phenomena and cellular differentiation.Furthermore, we consider the combined role of both systems (ASC-TAC and RTGT) in tissue engineering and in pathological processes, such as fibrosis, organization, atherosclerosis, and tumor stroma.
Topics: Adult; Animals; Cell Differentiation; Cell Division; Granulation Tissue; Humans; Inflammation; Stem Cells; Tissue Engineering
PubMed: 19273139
DOI: 10.2741/3317 -
Annals of the Royal College of Surgeons... Dec 1951
Topics: Granulation Tissue; Humans; Regeneration
PubMed: 14895111
DOI: No ID Found -
Journal of Wound Care Sep 2021This study aimed to collect and analyse real-life data to characterise the initial use of Hydrofiber Technology dressings for the management of exuding wounds in France.
OBJECTIVE
This study aimed to collect and analyse real-life data to characterise the initial use of Hydrofiber Technology dressings for the management of exuding wounds in France.
METHOD
An online survey of nurses provided data from patients managed with two dressings-AQUACEL Extra or AQUACEL Ribbon-as the primary dressing. At baseline, sociodemographic data, relevant medical histories and wound characteristics were recorded. The status of the wounds was then examined on days seven and 14 of management, together with scores of both clinician and patient satisfaction.
RESULTS
The survey included 1093 patients with a mean age of 65.9 years, comprising 53.3% women; 615 (56.3%) patients presented with acute wounds and 478 with hard-to-heal wounds. Wounds were reported to have healed or improved in 79.4% and 88.1% of the patients after 7 and 14 days, respectively. After 14 days, the wounds were smaller (p<0.001), and the percentage of sloughy wound bed tissue had decreased (p<0.001), while the percentage of granulation tissue and epithelialisation increased significantly (p=0.024 and p=0.047, respectively). Tolerance of the dressing was good, with low levels of pain reported, both while wearing the dressing and on removal. On day 14, nurses reported a high level of satisfaction, while 70% and 42.7% of patients with acute and hard-to-heal wounds, respectively, were 'very satisfied'.
CONCLUSION
The Hydrofiber Technology dressings aided wound healing when used in the management of a wide range of acute and hard-to-heal wounds in medical and surgical indications. User satisfaction was high from both healthcare professionals and patients.
Topics: Aged; Bandages; Carboxymethylcellulose Sodium; Female; Granulation Tissue; Humans; Male; Patient Satisfaction; Wound Healing
PubMed: 34554834
DOI: 10.12968/jowc.2021.30.9.763