scholarly journals Mechanosensitive Aspects of Cell Biology in Manual Scar Therapy for Deep Dermal Defects

2020 ◽  
Vol 21 (6) ◽  
pp. 2055
Author(s):  
Thomas Koller

Deep dermal defects can result from burns, necrotizing fasciitis and severe soft tissue trauma. Physiological scar restriction during wound healing becomes increasingly relevant in proportion to the affected area. This massively restricts the general mobility of patients. External mechanical influences (activity or immobilization in everyday life) can lead to the formation of marked scar strands and adhesions. Overloading results in a renewed inflammatory reaction and thus in further restriction. Appropriate mechanical stimuli can have a positive influence on the scar tissue. “Use determines function,” and even minimal external forces are sufficient to cause functional alignment (mechanotransduction). The first and second remarkable increases in connective tissue resistance (R1 and R2) seem to be relevant clinical indications of adequate dosage in the proliferation and remodulation phase, making it possible to counteract potential overdosage in deep dermal defects. The current state of research does not allow a direct transfer to the clinical treatment of large scars. However, the continuous clinical implementation of study results with regard to the mechanosensitivity of isolated fibroblasts, and the constant adaptation of manual techniques, has nevertheless created an evidence-base for manual scar therapy. The manual dosages are adapted to tissue physiology and to respective wound healing phases. Clinical observations show improved mobility of the affected regions and fewer relapses into the inflammatory phase due to mechanical overload.

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.


Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Jiajia Chang ◽  
Xiaoqin He ◽  
Jingmei Hu ◽  
Peter Muiruri Kamau ◽  
Ren Lai ◽  
...  

Prokineticins are highly conserved small peptides family expressed in all vertebrates, which contain a wide spectrum of functions. In this study, a prokineticin homolog (Bv8-AJ) isolated from the venom of frog Amolops jingdongensis was fully characterized. Bv8-AJ accelerated full-thickness wounds healing of mice model by promoting the initiation and the termination of inflammatory phase. Moreover, Bv8-AJ exerted strong proliferative effect on fibroblasts and keratinocytes isolated from newborn mice by activating interleukin (IL)-1 production. Our findings indicate that Bv8 is a potent wound healing regulator and may reveal the mechanism of rapid wound-healing in amphibian skins.


Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Sara Marmolejo-Martínez-Artesero ◽  
David Romeo-Guitart ◽  
Vanesa Venegas ◽  
Mario Marotta ◽  
Caty Casas

Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.


2010 ◽  
Vol 191 (2) ◽  
pp. 237-248 ◽  
Author(s):  
Ellen A. Lumpkin ◽  
Kara L. Marshall ◽  
Aislyn M. Nelson

The sense of touch detects forces that bombard the body’s surface. In metazoans, an assortment of morphologically and functionally distinct mechanosensory cell types are tuned to selectively respond to diverse mechanical stimuli, such as vibration, stretch, and pressure. A comparative evolutionary approach across mechanosensory cell types and genetically tractable species is beginning to uncover the cellular logic of touch reception.


2012 ◽  
Vol 196 (5) ◽  
pp. 553-562 ◽  
Author(s):  
Ryan S. King ◽  
Phillip A. Newmark

Regeneration of complex structures after injury requires dramatic changes in cellular behavior. Regenerating tissues initiate a program that includes diverse processes such as wound healing, cell death, dedifferentiation, and stem (or progenitor) cell proliferation; furthermore, newly regenerated tissues must integrate polarity and positional identity cues with preexisting body structures. Gene knockdown approaches and transgenesis-based lineage and functional analyses have been instrumental in deciphering various aspects of regenerative processes in diverse animal models for studying regeneration.


2021 ◽  
Author(s):  
Katerina Menclová ◽  
Petr Svoboda ◽  
Jan Hadač ◽  
Štefan Juhás ◽  
Jana Juhásová ◽  
...  

ABSTRACT Background Nanofiber wound dressings remain the domain of in vitro studies. The purpose of our study was to verify the benefits of chitosan (CTS) and polylactide (PLA)-based nanofiber wound dressings on a porcine model of a naturally contaminated standardized wound and compare them with the conventional dressings, i.e., gauze and Inadine. Material and Methods The study group included 32 pigs randomized into four homogeneous groups according to the wound dressing type. Standardized wounds were created on their backs, and wound dressings were regularly changed. We evaluated difficulty of handling individual dressing materials and macroscopic appearance of the wounds. Wound swabs were taken for bacteriological examination. Blood samples were obtained to determine blood count values and serum levels of acute phase proteins (serum amyloid A, C-reactive protein, and haptoglobin). The crucial point of the study was histological analysis. Microscopic evaluation was focused on the defect depth and tissue reactions, including formation of the fibrin exudate with neutrophil granulocytes, the layer of granulation and cellular connective tissue, and the reepithelialization. Statistical analysis was performed by using SPSS software. The analysis was based on the Kruskal–Wallis H test and Mann–Whitney U test followed by Bonferroni correction. Significance was set at P < .05. Results Macroscopic examination did not show any difference in wound healing among the groups. However, evaluation of histological findings demonstrated that PLA-based nanofiber dressing accelerated the proliferative (P = .025) and reepithelialization (P < .001) healing phases, while chitosan-based nanofiber dressing potentiated and accelerated the inflammatory phase (P = .006). No statistically significant changes were observed in the blood count or acute inflammatory phase proteins during the trial. Different dynamics were noted in serum amyloid A values in the group treated with PLA-based nanofiber dressing (P = .006). Conclusion Based on the microscopic examination, we have documented a positive effect of nanofiber wound dressings on acceleration of individual phases of the healing process. Nanofiber wound dressings have a potential to become in future part of the common wound care practice.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Jinglian Yan ◽  
Guodong Tie ◽  
Lyne Khair ◽  
Elena Filippova ◽  
Louis Messina

Rationale: People with Type 2 Diabetes Mellitus (T2DM) have a 25x higher risk of limb loss than non-diabetics due in large part to impaired wound healing. The mechanisms that cause impaired wound healing remain incompletely characterized. Objective: We hypothesize that T2DM impairs wound healing by epigenetic modifications in hematopoietic stem cells (HSC) that reduce their differentiation towards monocytes/macrophages and disrupts the balance in M1/M2 polarization during the three phases of wound healing. Methods and Results: Wounds were created on the back of mice. Wound healing was significantly slower in diabetic db/db than in WT mice. During the early inflammatory phase, db/db wounds exhibited a significant decrease in total macrophages and M1 macrophages. Then, total macrophages and M2 macrophages were decreased, while M1 macrophages increased in tissue formation phase. In the late tissue remodeling phase, total macrophages and M1 macrophages were persistently increased. The impaired wound healing phenotype of db/db mice was recapitulated in WT recipients which were resconstituted with db/db HSCs, demonstrating that the impaired differentiation of HSCs towards macrophages as well as their M1/M2 polarization was due to a cell autonomous mechanism. Epigenetic studies indicated that DNMT1-dependent hypermethylation of Notch1, Pu.1 and KLF4 in T2D HSCs was responsible for the impaired differentiation towards monocytes/macrophages as well as the skewed M1/M2 polarization. Knockdown of DNMT1 in HSCs from db/db mice transplanted into lethally irradiated WT mice led to improved wound healing by an increase in macrophage infiltration as well as a normalization of the M1/M2 polarization. Conclusion: This study indicates that the dynamic changes of macrophage concentration and M1/M2 polarization in wound healing are regulated at the level of HSCs. Moreover, T2DM impairs wound healing by inducing DNMT1-dependent reduction of HSCs’ differentiation towards macrophages and their M1/M2 polarization. This novel finding indicates that inflammation is regulated at the level of HSCs, which creates new opportunities to develop epigenetic modification related therapies for T2DM and potentially other conditions that result from dysinflammation.


2018 ◽  
Vol 26 (5) ◽  
pp. 342-345 ◽  
Author(s):  
Daniel Baumfeld ◽  
Tiago Baumfeld ◽  
Benjamim Macedo ◽  
Roberto Zambelli ◽  
Fernando Lopes ◽  
...  

ABSTRACT Objective: There are no specific criteria that define the level of amputation in diabetic patients. The objective of this study was to assess the influence of clinical and laboratory parameters in determining the level of amputation and the wound healing time. Methods: One hundred and thirty-nine diabetic patients were retrospectively assessed. They underwent surgical procedures due to infection and/or ischemic necrosis. Type of surgery, antibiotic use, laboratory parameters and length of hospital stay were evaluated in this study. Results: The most common amputation level was transmetatarsal, occurring in 26 patients (28.9%). The wound healing time increased with statistical significance in individuals undergoing debridement, who did not receive preoperative antibiotics and did not undergo vascular intervention. Higher levels of amputation were statistically related to limb ischemia, previous amputation and non-use of preoperative antibiotics. Conclusion: Patients with minor amputations undergo stump revision surgery more often, but the act of always targeting the most distal stump possible decreases energy expenditure while walking, allowing patients to achieve better quality of life. Risk factors for major amputations were ischemia and previous amputations. A protective factor was preoperative antibiotic therapy. Level of Evidence III, Retrospective Study.


2018 ◽  
Vol 52 (9/10) ◽  
pp. 2128-2150
Author(s):  
Timucin Ozcan ◽  
Ahmet M. Hattat ◽  
Michael Hair

Purpose This paper aims to investigate the effectiveness of positioning unknown ingredients either with the presence or absence of framing; both are common in marketplace (e.g. Secret® deodorant visibly claims “aluminum chlorohydrate” while Crystal® promotes “no aluminum chlorohydrate”). Design/methodology/approach The authors used three scenario-based experiments. The participants were recruited through Amazon Mechanical Turk online panel and randomly assigned to a variety of experimental conditions. Findings Initial study results show that consumers have more positive evaluations and purchase intentions for absence positioning than presence positioning, because absence positioning induces greater perceptions of protection. In the second study, these results are extended using multiple ingredients, along with competitor products; they show that absence positioning leads to better evaluations than presence positioning and replicate the mediation effect that was found earlier. In the final study, through manipulating participants’ regulatory focus, the authors show that absence-positioned ingredients have a higher choice share when consumers are in the prevention mindset. Conversely, when customers are in promotion mindset and looking for better performance, presence positioning of ingredients seems to have higher choice shares. Research limitations/implications The research has implications for product development, promotions, labeling and packaging, showing the positive influence of absence positioning of unknown ingredients. Practical implications Marketers may emphasize the absence of unknown ingredients in their products instead of following a strategy that highlights the inclusion of them. Originality/value To the authors’ extant knowledge, this research is an initial attempt to understand how consumers react to promotion of product ingredients. In addition, it contributes to the literature in unknown attributes by showing that absence positioning of certain types of ingredients is perceived better than presence framing of them.


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