Effects of uniaxial stretching on tenocyte migration behaviour

AbstractIt is widely known that tendon tissues are subjected to repeated cyclic mechanical load which influences cellular processes. The involvement of principles of mechanics in tissue engineering contributes to the investigations of the connection between mechanical and biological parameters in cellular processes and as well as to the development of new approaches for specific treatment methods. The healing process of injured tendons includes tenocyte migration which occurs from intact regions of tendon into the wound site. The aim of the present study is to investigate and enhance the migration characteristics of tenocytes under uniaxial mechanical stretching using an in-house tensile bioreactor system. Uniaxial mechanical stretching is applied to tenocyte-seeded silicone as well as collagen membranes, which possess different material properties. Tenocyte-seeded silicone membranes were investigated under three different loading conditions, including unstimulated (control), 3% and 5% strain, at frequency of 0.5 Hz. Tenocyte-seeded collagen membranes were investigated using three different frequencies, including unstimulated (control), 0.1 Hz and 0.5 Hz at strain of 4%. The main finding in this study is that uniaxially mechanical stretching at 3% strain enhances the cell migration more than 5% strain on silicone membranes.

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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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Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

Medical Sciences ◽

10.3390/medsci9010016 ◽

2021 ◽

Vol 9 (1) ◽

pp. 16

Author(s):

Renato Francesco Maria Scalise ◽

Rosalba De Sarro ◽

Alessandro Caracciolo ◽

Rita Lauro ◽

Francesco Squadrito ◽

...

Keyword(s):

Myocardial Infarction ◽

Signaling Pathways ◽

Ventricular Dysfunction ◽

Healing Process ◽

Molecular Signaling ◽

Cellular Processes ◽

Molecular Signaling Pathways ◽

Fibrotic Scar ◽

Life Threatening

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

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Impaired wound healing in embryonic and adult mice lacking vimentin

Journal of Cell Science ◽

10.1242/jcs.113.13.2455 ◽

2000 ◽

Vol 113 (13) ◽

pp. 2455-2462 ◽

Cited By ~ 8

Author(s):

B. Eckes ◽

E. Colucci-Guyon ◽

H. Smola ◽

S. Nodder ◽

C. Babinet ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Wild Type ◽

Impaired Wound Healing ◽

Wound Site ◽

Adult Mice ◽

Tractional Forces ◽

Filament Network ◽

Vimentin Intermediate Filament

It is generally assumed that the vimentin intermediate filament network present in most mesenchymally-derived cells is in part responsible for the strength and integrity of these cells, and necessary for any tissue movements that require the generation of significant tractional forces. Surprisingly, we have shown that transgenic KO mice deficient for vimentin are apparently able to undergo embryonic development absolutely normally and go onto develop into adulthood and breed without showing any obvious phenotype. However, fibroblasts derived from these mice are mechanically weak and severely disabled in their capacity to migrate and to contract a 3-D collagen network. To assess whether these functions are necessary for more challenging tissue movements such as those driving in vivo tissue repair processes, we have analysed wound healing ability in wild-type versus vimentin-deficient embryos and adult mice. Wounds in vimentin-deficient adult animals showed delayed migration of fibroblasts into the wound site and subsequently retarded contraction that correlated with a delayed appearance of myofibroblasts at the wound site. Wounds made to vimentin-deficient embryos also failed to heal during the 24 hour culture period it takes for wild-type embryos to fully heal an equivalent wound. By DiI marking the wound mesenchyme and following its fate during the healing process we showed that this impaired healing is almost entirely due to a failure of mesenchymal contraction at the embryonic wound site. These observations reveal an in vivo phenotype for the vimentin-deficient mouse, and challenge the dogma that key morphogenetic events occurring during development require generation of significant tractional forces by mesenchymal cells.

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E11/gp38 Selective Expression in Osteocytes: Regulation by Mechanical Strain and Role in Dendrite Elongation

Molecular and Cellular Biology ◽

10.1128/mcb.02120-05 ◽

2006 ◽

Vol 26 (12) ◽

pp. 4539-4552 ◽

Cited By ~ 170

Author(s):

Keqin Zhang ◽

Cielo Barragan-Adjemian ◽

Ling Ye ◽

Shiva Kotha ◽

Mark Dallas ◽

...

Keyword(s):

Shear Stress ◽

Cell Lines ◽

Mechanical Load ◽

Mechanical Strain ◽

Three Dimensional ◽

Cell Communication ◽

Bone Surface ◽

Cellular Processes ◽

Primary Osteoblasts

ABSTRACT Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells. Bone extracts contain large amounts of E11, but immunostaining only shows its presence in early osteocytes compared to more deeply embedded cells, suggesting epitope masking by mineral. Freshly isolated primary osteoblasts are negative for E11 expression but begin to express this protein in culture, and expression increases with time, suggesting differentiation into the osteocyte phenotype. Osteoblast-like cell lines 2T3 and Oct-1 also show increased expression of E11 with differentiation and mineralization. E11 is highly expressed in MLO-Y4 osteocyte-like cells compared to osteoblast cell lines and primary osteoblasts. Differentiated, mineralized 2T3 cells and MLO-Y4 cells subjected to fluid flow shear stress show an increase in mRNA for E11. MLO-Y4 cells show an increase in dendricity and elongation of dendrites in response to shear stress that is blocked by small interfering RNA specific to E11. In vivo, E11 expression is also increased by a mechanical load, not only in osteocytes near the bone surface but also in osteocytes more deeply embedded in bone. Maximal expression is observed not in regions of maximal strain but in a region of potential bone remodeling, suggesting that dendrite elongation may be occurring during this process. These data suggest that osteocytes may be able to extend their cellular processes after embedment in mineralized matrix and have implications for osteocytic modification of their microenvironment.

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Alginate hydrogel enriched with Ambystoma mexicanum epidermal lipoxygenase-loaded pectin nanoparticles for enhanced wound healing

Journal of Biomaterials Applications ◽

10.1177/0885328219896704 ◽

2019 ◽

Vol 34 (8) ◽

pp. 1171-1187

Author(s):

Farnoush Oveissi ◽

Naser Tavakoli ◽

Mohsen Minaiyan ◽

Mohammad Reza Mofid ◽

Azade Taheri

Keyword(s):

Wound Healing ◽

Wound Closure ◽

Healing Process ◽

Ambystoma Mexicanum ◽

Wound Healing Process ◽

Clinical Use ◽

Sustained Delivery ◽

Alginate Hydrogel ◽

Wound Site ◽

Minimal Scarring

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.

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The emerging roles of neutrophil extracellular traps in wound healing

Cell Death and Disease ◽

10.1038/s41419-021-04294-3 ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Shuainan Zhu ◽

Ying Yu ◽

Yun Ren ◽

Liying Xu ◽

Huilin Wang ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Neutrophil Extracellular Traps ◽

Neutrophil Extracellular Trap ◽

Wound Healing Process ◽

Loss Of Function ◽

Delayed Wound Healing ◽

Wound Site ◽

Extracellular Traps ◽

Extracellular Trap

AbstractDelayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.

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An Overview of the Role of Mechanical Stretching in the Progression of Lung Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.781828 ◽

2021 ◽

Vol 9 ◽

Author(s):

Fengying Gong ◽

Yuchao Yang ◽

Liangtao Wen ◽

Congrong Wang ◽

Jingjun Li ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Mechanical Load ◽

Tumor Development ◽

Physical Factors ◽

Mechanical Factors ◽

Tissue Characteristics ◽

The Relationship ◽

Mechanical Stretching

Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.

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Collagen membranes for skin wound repair: A systematic review

Journal of Biomaterials Applications ◽

10.1177/0885328220980278 ◽

2020 ◽

pp. 088532822098027

Author(s):

Tiago Akira Tashiro Araujo ◽

Matheus Cruz Almeida ◽

Ingrid Avanzi ◽

Julia Parisi ◽

Abdias Fernando Simon Sales ◽

...

Keyword(s):

Systematic Review ◽

Wound Healing ◽

Healing Process ◽

Biological Tissues ◽

Skin Wound ◽

Wound Healing Process ◽

Skin Wound Healing ◽

Efficient Treatment ◽

Positive Effects ◽

Collagen Membranes

Membranes or skin dressing are common treatments for skin wound injuries, collagen being one the most effective materials for their manufacturing. Many different sources of collagen with diverse methods of extraction and processing have been used, with evidence of positive effects on the stimulation of skin wound healing. In spite of these factors, there is still limited understanding of the interaction between collagen membranes and biological tissues, especially due to the series of different types of collagen origin. In this context, this study aimed to conduct a systematic review of the available literature examining the effect of various collagen membranes for accelerating skin wound healing in experimental animal models and clinical trials. The present review was performed from March to May of 2020 searching in two databases (PubMed and Scopus). The following Medical Subject Headings (MeSH) descriptors were used: “collagen”, “dressing”, “membranes”, “skin” and “wound”. After the eligibility assessment, 16 studies were included and analyzed. The studies demonstrated that collagen was obtained predominantly from bovine and porcine sources, by acetic acid and/or enzyme dissolution. Additionally, most of the studies demonstrated that the membranes were processed mainly by freeze-drying or lyophilization methods. All the in vivo and clinical trial studies evidenced positive outcomes in the wound healing process, thus confirming that collagen membranes are one of the most efficient treatment for skin wounds, highlighting the enormous potential of this biomaterial to be used for skin tissue engineering purposes.

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Ulcers as a Sign of Skin Infection with Mycobacterium wolinskyi: Report of a Case and Review of the Literature

Case Reports in Dermatology ◽

10.1159/000446470 ◽

2016 ◽

Vol 8 (2) ◽

pp. 151-156 ◽

Cited By ~ 4

Author(s):

Simon Bossart ◽

Barbara Schnell ◽

Katrin Kerl ◽

Mirjana Urosevic-Maiwald

Keyword(s):

Clinical Symptoms ◽

Healing Process ◽

Specific Treatment ◽

Surgical Excision ◽

16S Rrna Gene Sequencing ◽

Insulin Injection ◽

Rrna Gene ◽

High Morbidity ◽

Ulcer Formation ◽

Rrna Gene Sequencing

Infection with Mycobacterium wolinskyi, if not detected, may cause severe skin and soft tissue infection with prolonged healing process and is therefore associated with high morbidity. Only about 20 cases of M. wolinskyi infections in humans have been described in the literature until now, none of them in Switzerland. We report a case of an infection in a 72-year-old male patient with recurrent subcutaneous abdominal wall abscesses and ulcer formation after insulin injection in the underbelly. A culture of skin biopsy tissue showed rapid growth of non-tuberculous mycobacteria (NTM), which were identified by 16S rRNA gene sequencing as M. wolinskyi. Surgical excision and primary closure of all abdominal ulcers in combination with antibiotic therapy, based on the antimicrobiotic susceptibility test results, were performed and resulted in complete resolution of the clinical symptoms and no recurrence of infection at a 6-month follow-up. The present case emphasizes the importance of accurate diagnosis and treatment of chronic infection with ulcer formation. In such cases, it is crucial to consider the presence of NTM, such as M. wolinskyi, in order to obtain rapid diagnosis, specific treatment and improved patient care.

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Wound Healing In Glaucoma

Complications of Glaucoma Surgery ◽

10.1093/oso/9780195382365.003.0013 ◽

2013 ◽

Author(s):

Kimberly A. Mankiewicz ◽

Leonard K. Seibold

Keyword(s):

Wound Healing ◽

Blood Cells ◽

Healing Process ◽

White Blood Cells ◽

Glaucoma Surgery ◽

Scar Formation ◽

Wound Site ◽

Normal Wound Healing ◽

Inflammatory Phase ◽

Repair Phase

The goal of wound healing in most surgeries is to bring the injured tissue back to its original state to prevent the wound from reopening. However, in glaucoma surgery, the goal is to have incomplete wound healing. Scar formation prevents the filtering mechanism and bleb from functioning properly, leading to poor pressure control and failure of the surgery. However, if there is too little wound healing, surgical failure may be marked by overfiltration and hypotony. Several modulators are currently used in conjunction with glaucoma surgery, and new targets are under investigation to improve our ability to control the healing process. Normal wound healing occurs in 3 phases: the inflammatory phase, the proliferative/repair phase, and the remodeling phase. In the inflammatory phase, blood cells and plasma proteins are released around the wound site. These proteins attract other wound healing factors, such as cytokines and growth factors. White blood cells are also recruited to the site, clearing out undesired cellular debris through phagocytosis. Additionally, platelet aggregation and fibrin clot formation occur. In the proliferative/repair phase, fibroblasts, crucial cells for tissue repair and scarring, begin reforming the extracellular matrix (ECM) and other components of connective tissue. Angiogenesis also occurs, and the wound begins to close. In the final phase, blood vessels are resorbed and fibroblasts disperse. Fibroblasts produce matrix metalloproteinases that, along with collagen and elastin, allowing for wound remodeling and scar formation. The modulators used in glaucoma surgery, as well as new agents in development, disrupt various aspects of this cycle. Use of topical corticosteroids in conjunction with filtering surgery is a routine part of postoperative management and has been for many decades. Corticosteroids blunt the wound healing response by altering the inflammatory phase through reducing the amount of inflammatory cells and cytokines that migrate to the wound site. Corticosteroids also prevent the complexing and conversion of inflammatory mediators, as well as reduce vascular permeability to limit mobility of wound healing factors to the wound site.

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