Remodeling Phase Research Articles

Praktik Khitan dengan Metode Sunathrone Klamp Perspektif Hukum Islam (Studi Kasus di Smart Care Center Makassar)

This study aimed to examine the practice of circumcision using the Sunathrone Klamp method at the Makassar Smart Care Center Clinic in a review of Islamic law. This research used field research using normative theological approaches and health approaches. Data collection techniques were conducted through observation, interviews, and documentation. The research results found; 1) The healing process of the circumcision wound has a phase in 3 weeks (21 days), in which the skin will return to its original shape. There are three phases of wound healing after circumcision using the Sunathrone Klamp method, namely the inflammation phase, the proliferation phase, and the remodeling phase; 2) The advantages of the Sunathrone Klamp include a relatively short time, no stitches, minimizing pain, psychologically the child feels comfortable when circumcised, and relatively fast healing time. The drawbacks after circumcision are that the patient feels uncomfortable because the clamp will be installed in a few days, and has a high level of operational standards, so that it is only used by experts in the field; and 3) Sunathrone Klamp is a practical tool for circumcision or circumcision with an easier, safer, and hygienic working process. In a review of Islamic law, the Sunathrone Klamp method is permissible, as long as the circumcision process is carried out by an expert or professional.

In vivo investigation of 3D printed polycaprolactone/graphene electro-active bone scaffolds

Additive manufactured scaffolds are widely used as 3D support structures for tissue engineering. This paper investigates the mechanisms behind bone regeneration due to the combined use of 3D printed poly (ϵ-caprolactone)/graphene (PCL/G) electro-active scaffolds and electrical stimulation. A comprehensive in vivo study was conducted to assess the proposed approach, using a rat model. Results show that the combined use of electro-active scaffolds and electrical stimulation therapy accelerates the bone regeneration process and the formation of more organized new bone, through fast angiogenesis, and a rapid transition to the mineralization and bone remodelling phase. The mechanism is investigated and explained.

A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa With Skin and Oesophagus.

Epithelial tissues are the most rapidly dividing tissues in the body, holding a natural ability for renewal and regeneration. This ability is crucial for survival as epithelia are essential to provide the ultimate barrier against the external environment, protecting the underlying tissues. Tissue stem and progenitor cells are responsible for self-renewal and repair during homeostasis and following injury. Upon wounding, epithelial tissues undergo different phases of haemostasis, inflammation, proliferation and remodelling, often resulting in fibrosis and scarring. In this review, we explore the phenotypic differences between the skin, the oesophagus and the oral mucosa. We discuss the plasticity of these epithelial stem cells and contribution of different fibroblast subpopulations for tissue regeneration and wound healing. While these epithelial tissues share global mechanisms of stem cell behaviour for tissue renewal and regeneration, the oral mucosa is known for its outstanding healing potential with minimal scarring. We aim to provide an updated review of recent studies that combined cell therapy with bioengineering exporting the unique scarless properties of the oral mucosa to improve skin and oesophageal wound healing and to reduce fibrotic tissue formation. These advances open new avenues toward the ultimate goal of achieving scarless wound healing.

Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients

In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.

Current Advances in Hypertrophic Scar and Keloid Management.

Hypertrophic scars and keloids are caused by excessive tissue response to dermal injury due to local fibroblast proliferation and collagen overproduction. This response occurs because of pathologic wound healing due to dysregulation in the inflammatory, proliferative, and/or remodeling phase. Patients with hypertrophic scars or keloids report reduced quality of life, physical status, and psychological health. Hypertrophic scars or keloids will develop in 30 to 90% of individuals, and despite their prevalence, treatment remains a challenge. Of the treatments currently available for hypertrophic scars and keloids few have been adequately supported by studies with appropriate experimental design. Here, we aim to review the available literature to provide up-to-date information on the etiology, epidemiology, histology, pathophysiology, prevention, and management options available for the treatment of hypertrophic scars and keloids and highlight areas where further research is required.

Updates in Diabetic Wound Healing, Inflammation, and Scarring.

Diabetic patients can sustain wounds either as a sequelae of their disease process or postoperatively. Wound healing is a complex process that proceeds through phases of inflammation, proliferation, and remodeling. Diabetes results in several pathological changes that impair almost all of these healing processes. Diabetic wounds are often characterized by excessive inflammation and reduced angiogenesis. Due to these changes, diabetic patients are at a higher risk for postoperative wound healing complications. There is significant evidence in the literature that diabetic patients are at a higher risk for increased wound infections, wound dehiscence, and pathological scarring. Factors such as nutritional status and glycemic control also significantly influence diabetic wound outcomes. There are a variety of treatments available for addressing diabetic wounds.

EARLY OUTCOMES AFTER SUTURE TAPE REINFORCEMENT OF QUADRICEPS TENDON AUTOGRAFT ACL RECONSTRUCTION IN ADOLESCENT ATHLETES

Background:Recently, anterior cruciate ligament reconstruction (ACLR) with suture-tape reinforcement has been popularized for protection of the graft during the revascularization and remodeling phase of incorporation. To date, there are limited short-term data regarding the outcomes of suture tape reinforcement to ACLR. Furthermore, its use with quadriceps tendon autograft (QT) ACLR is limited.Purpose:The purpose of this study was to review the early, preliminary results of ACLR in adolescent patients using QT autograft with suture tape reinforcement (QT-SR).Methods:A retrospective review was performed of skeletally mature adolescent patients who underwent primary ACLR with all-soft tissue QT-SR since 2018. Surgeries were performed by a single surgeon using an all-inside technique. All patients followed the same standardized rehabilitation protocol. Twelve-month patient-reported outcome measures (PROMs) and complications were analyzed. PROMs included the Pediatric International knee Documentation Committee (Pedi-IKDC) Subjective Knee Evaluation Form, Lysholm knee scoring scale, and the Tegner activity level scale. Psychological readiness was assessed with the ACL-Return to Sport after Injury (ACL-RSI) scale.Results:39 patients (24 girls, 15 boys) were identified. The mean age at the time of surgery was 15.7 ± 1.3 years (range, 13-18 years). 82% of patients were high school athletes. Soccer was the primary sport for 48.7% of patients. The mean graft diameter was 9.5 ± 0.4 mm. 51.3% of patients had concomitant meniscus repairs. The mean time to return-to-sport clearance was 10.1 ± 1.4 months. At 12 months, the mean postoperative Pedi-IKDC was 95.6 ± 4.0, the mean Lysholm score was 97.6 ± 3.9, and the mean Tegner score was 8.8 ± 0.9. All PROMs improved significantly compared to the preoperative scores (Pedi-IKDC: p = 0.003, Lysholm: p = 0.006, Tegner: p = 0.003). The mean ACL-RSI was 93.4 ± 4.7. Complications included return to surgery due to postoperative stiffness in two patients. There were no cases of postoperative instability, graft rupture, or contralateral ACL injury.Conclusion:QT-SR ACLR results in excellent clinical and patient-reported outcomes in adolescent athletes at 12 months follow-up. The long-term effect of QT-SR remains to be investigated.

Identification of potential hub genes associated with skin wound healing based on time course bioinformatic analyses

BackgroundThe skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer.MethodsGene expression profiles of 37 biopsies collected from patients undergoing split-thickness skin grafts at five different time points were downloaded from two datasets (GSE28914 and GSE50425) in the Gene Expression Omnibus (GEO) database. Principal component analysis (PCA) was applied to classify samples into different phases. Subsequently, differentially expressed genes (DEGs) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment analyses were performed, and protein–protein interaction (PPI) networks created for each phase. Furthermore, based on the results of the PPI, hub genes in each phase were identified by molecular complex detection combined with the ClueGO algorithm.ResultsUsing principal component analysis, the collected samples were divided into four phases, namely intact phase, acute wound phase, inflammatory and proliferation phase, and remodeling phase. Intact samples were used as control group. In the acute wound phase, a total of 1 upregulated and 100 downregulated DEGs were identified. Tyrosinase (TYR), tyrosinase Related Protein 1 (TYRP1) and dopachrome tautomerase (DCT) were considered as hub genes and enriched in tyrosine metabolism which dominate the process of melanogenesis. In the inflammatory and proliferation phase, a total of 85 upregulated and 164 downregulated DEGs were identified. CHEK1, CCNB1 and CDK1 were considered as hub genes and enriched in cell cycle and P53 signaling pathway. In the remodeling phase, a total of 121 upregulated and 49 downregulated DEGs were identified. COL4A1, COL4A2, and COL6A1 were considered as hub genes and enriched in protein digestion and absorption, and ECM-receptor interaction.ConclusionThis comprehensive bioinformatic re-analysis of GEO data provides new insights into the molecular pathogenesis of wound healing and the potential identification of therapeutic targets for the treatment of wounds.

Dynamics of cytokines in osteosis splinter fractures replacement in dogs with hydroxyapatite ceramics silicon-doped

Among the entire public of fractures of long bones, more complications of reparative osteogenesis occur fragmental fractures. Their significant defects, which arise as a result of the removal of non-viable fragments, cause disturbances in local hemodynamics and microcirculation and loss of osteoconduction in the area of injury, lead to a loss of the reparative potential of bone tissue in the defect zone, and the methods of osteosynthesis do not provide restoration of osteoconduction and do not have osteointegration properties. For osteosis, a number of composite materials have been proposed, among which ceramics based on calcium phosphates are considered the most promising, which is confirmed by previous clinical, radiological and histomorphological studies. The aim of the study is to determine the dynamics of the blood levels of TGF-β and interleukins IL-1β and IL-10 for osteosis replacement of splinter bone fractures in dogs with calcium phosphate ceramics doped with silicon. Material and research methods: a control (n = 7) and research group (n = 7) dogs with accidental splinter fractures of long bones were formed. In both groups, extracortical osteosynthesis was performed with a support plate from an unalloyed titanium alloy. In the control group, bone defects were left to heal under a blood clot, and in the experimental group they were replaced with ceramics (GTlKg-3). Blood samples were taken after trauma no later than on the 48th day, and on the third, twelfth, twenty-first, forty-second and 60th days after surgical treatment. The enzyme immunoassay was used to determine the serum levels of interleukins IL-1β and IL-10 and transforming growth factor (TGF-β) тhat for a bureta reaction is a bit of a home-made bottle. The study results showed an anti-inflammatory cytokine profile with physiological norms in dogs. In case of bone injury, it becomes pro-inflammatory in nature, triggers the process of osteoresorption in the fracture area. At the same time, during reparative osteogenesis after extracortical osteosynthesis for splinter fractures, proinflammatory cytokinemia acquires a permanent character with a peak on the forty-second day, and this implies inhibition of metaplasia of cartilaginous regenerate into bone, that is, it slows down the consolidation of the fracture. However, in the case of osteosis with ceramics, the level of pro-inflammatory cytokinemia is significantly lower and continues during the first 12 days with a peak on the third day, during the inflammatory-resorptive stage. However, the key in understanding the effectiveness of osteosis was the dynamics of TGF-β, which showed its biphasic hyperreactivity in control animals, while in experimental animals, its balanced production was noted. Conclusion. Osteosis replacement of bone defects in long tubular bones in dogs with hydroxyapatite with β-tricalcium phosphate ceramics doped with silicon is accompanied by moderate cytokinemia in accordance with the course of the inflammatory-resorptive stage and the phase of remodeling with a peak of induction of transforming growth factor during the period of active osteogenesis forty-second course of reparative osteogenesis.

An ultrasmall infinite coordination polymer nanomedicine-composited biomimetic hydrogel for programmed dressing-chemo-low level laser combination therapy of burn wounds

To programmatically promote burn wound healing in a way that was tailored to the complex healing phases of hemostasis, anti-inflammation, proliferation, and remolding, we proposed a combined therapeutic strategy of dressing management-chemotherapy-low level laser therapy (LLLT), and designed a highly integrated and simply-structured nanocomposite hydrogel with properties of transparency, self-monitored pH-responsive drug release, and burn wound-adaptability (shape-remodeling, self-healing, and tissue-adhesion). This nanocomposite hydrogel was composed of oxidized hyaluronic acid (OHA), ε-poly-L-lysine grafted human-like collagen (HLC-EPL) and a versatile curcumin-Fe(III) infinite coordination polymer nanomedicines (Cur-Fe(III) ICPs), which were dual dynamically cross-linked via imine bonds and nanoparticle-polymer interactions. The minimized light scattering and absorption of carrier-free and ultrasmall (9.14 ± 1.25 nm) Cur-Fe(III) ICPs and the low refractive index contrast with water of HLC-EPL and OHA endowed the nanocomposite hydrogel with a light transmittance of ≥ 90.1% at 904 nm, which made it compatible with LLLT. The dynamic crosslinking site-rich surface of the Cur-Fe(III) ICPs improved the shape-remodeling and self-healing efficiency of dressing, which resulted in an 84.6% cross-linking reconstruction efficiency within 10 min, thus making it more adaptive to burn wounds. The programmed therapy was implemented by the autoprogressed intrinsic procoagulant activity of HLC-EPL and physical sealing effect in the hemostasis phase, pH-responsive chemotherapy of Cur-Fe(III) ICPs in the inflammation phase, and spatiotemporally controllable LLLT in the proliferation and remodeling phases. As a result, the closure period of full-thickness burn wounds was greatly shortened from 21 to 9 days, and the reconstruction of skin structure was accelerated.

Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks.

Sprouting angiogenesis is an essential vascularization mechanism consisting of sprouting and remodelling. The remodelling phase is driven by rearrangements of endothelial cells (ECs) within the post-sprouting vascular plexus. Prior work has uncovered how ECs polarize and migrate in response to flow-induced wall shear stress (WSS). However, the question of how the presence of erythrocytes (widely known as red blood cells (RBCs)) and their impact on haemodynamics affect vascular remodelling remains unanswered. Here, we devise a computational framework to model cellular blood flow in developmental mouse retina. We demonstrate a previously unreported highly heterogeneous distribution of RBCs in primitive vasculature. Furthermore, we report a strong association between vessel regression and RBC hypoperfusion, and identify plasma skimming as the driving mechanism. Live imaging in a developmental zebrafish model confirms this association. Taken together, our results indicate that RBC dynamics are fundamental to establishing the regional WSS differences driving vascular remodelling via their ability to modulate effective viscosity.

Changes in macrophage and inflammatory cytokine expressions during fracture healing in an ovariectomized mice model

BackgroundMacrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis have not been fully revealed.MethodsTibia transverse fracture was established 12 weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-α, interleukin-6, interleukin-1β and macrophage conversion related molecules in the fracture haematoma or callus were also detected.ResultsThe processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-1β, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-α were decreased at 1, 14 and 21 days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice.ConclusionsThe expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.

TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing.

Collagen in Wound Healing.

Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided.

Development and Evaluation of Rifampicin Loaded Alginate-Gelatin Biocomposite Microfibers.

Various systematic phases such as inflammation, tissue proliferation, and phases of remodeling characterize the process of wound healing. The natural matrix system is suggested to maintain and escalate these phases, and for that, microfibers were fabricated employing naturally occurring polymers (biopolymers) such as sodium alginate, gelatin and xanthan gum, and reinforcing material such as nanoclay was selected. The fabrication of fibers was executed with the aid of extrusion-gelation method. Rifampicin, an antibiotic, has been incorporated into a biopolymeric solution. RF1, RF2, RF3, RF4 and RF5 were coded as various formulation batches of microfibers. The microfibers were further characterized by different techniques such as SEM, DSC, XRD, and FTIR. Mechanical properties and physical evaluations such as entrapment efficiency, water uptake and in vitro release were also carried out to explain the comparative understanding of the formulation developed. The antimicrobial activity and whole blood clotting of fabricated fibers were additionally executed, hence they showed significant results, having excellent antimicrobial properties; they could be prominent carriers for wound healing applications.

Methotrexate treatment in hand osteoarthritis refractory to usual treatments: A randomised, double-blind, placebo-controlled trial

ObjectiveTo examine the effect of methotrexate (MTX) on pain and structural progression in symptomatic erosive hand osteoarthritis (HOA). MethodsThis 1-year prospective, single-centre, randomised, double-blind, placebo-controlled study (www.ClinicalTrial.gov, NCT01068405) followed up patients with symptomatic erosive HOA. Patients were randomised into two groups based on the drug that was administered: 10 mg methotrexate (MTX) per week or a placebo. The primary endpoint was the change in pain (determined using a visual analogue scale [VAS]) from baseline to 3 months. The secondary endpoints were pain VAS score at 12 months, clinical features (pain VAS score and function), radiographic features (the anatomical radiographic Verbruggen–Veys [VV] score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months. ResultsSixty-four patients with HOA were randomised into either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in the pain VAS score (mm) (MTX: 21.1 [standard deviation, 27.4], placebo: 11.7 [24.3]; p = 0.2). At 12 months, according to the VV score, erosive joints progressed significantly more to a remodelling phase in the MTX group than in the placebo group (27% vs 15%; p = 0.03). Joints with space loss appeared to be eroding less in the MTX group compared to the placebo group (8% vs 29%; p = 0.2). Synovitis on MRI at baseline could be associated with the erosive structural evolution of non-erosive joints (p = 0.02). ConclusionsWeekly doses of 10-mg MTX showed no superiority over the placebo in terms of pain relief at 3 or 12 months.Clinical Trial Registration Number: This study was registered at www.ClinicalTrial.gov (NCT01068405).

Effect of Incorporation Platelet Rich Plasma into Synthetic Coral Scaffold toward Epithelial Thickness of Wound Healing

Tissue re-epithelialization is a process in wound healing. The healing process of wounds needs to pass through a phase of inflammatory, proliferation, and remodeling. Tissue engineering is the technology service in the field of medicine that can be applied in wound healing. A scaffold is a place for the molecule signal and cell growth to form new tissue. This study aims to investigate the ability of synthetic coral scaffold incorporated PRP in wound healing. Rattus norvegicus were used and divided into 4 groups, synthetic coral scaffold incorporated PRP, scaffold only, Spongostan, and control. The wound healing was observed on 3, 7, and 14 days by measuring the epithelial thickness. The average epithelium thickness on day 3 has not formed. The highest epithelial thickness on days 7 and 14 are obtained from the synthetic coral scaffolds incorporated by PRP. The result of this study presented that Synthetic coral scaffold incorporated by PRP has the highest ability for wound healing and increases the process of tissue regeneration.

Cardiac Fibrosis Following Myocardial Ischemia is Mitigated by Mesenchymal Stem Cell Exosomes

Objective Myocardial infarction is the leading cause of mortality worldwide. Following an ischemic event there is activation of macrophages and fibroblasts leading to scar formation. It is critical to limit the pro-fibrotic remodeling and activate the reparative, regenerative remodeling phase to limit cardiac diastolic dysfunction. We studied the effect of mesenchymal stem cell (MSC) exosomes on the extent of cardiac fibrosis in acute and chronic ischemia models. Methods Acute or chronic ischemia was induced in 8-10 week old healthy male wild-type mice by ligating the left coronary artery (LCA) for 1 hour or 7 days, respt. Mice were pretreated with MSC exosomes or saline as control. At 3 hrs (acute ischemia) or 7 days (chronic ischemia) after LCA ligation, the animals were euthanized and hearts were isolated. Hearts were sectioned into infarct and adjacent non-infarct areas and used for further studies. Results Following acute ischemia, there was activation of inflammatory signals, more in the peri-infarct than in the infarct area, in the saline treated mice. IL1b, LOX-1, PCSK9, and NFkB were overexpressed in the infarct areas. MSC exosome treatment reduced expression of IL1b, LOX-1, PCSK9, and NFkB in infarct areas of the LCA ligated mice hearts. At the same time, expression of cardiac remodeling signals (vimentin, collagens-1 and -3, fibronectin, MMP-2 and TIMP-2), was more in the infarct area. MSC exosomes treatment suppressed inflammatory signals during acute as well as chronic ischemia. Following chronic ischemia, we observed increased interstitial and peri-vascular fibrosis in saline treated mice hearts, which was suppressed by MSC exosome treatment. Proteomic analysis of the saline- and exosome-treated LCA ligated hearts revealed differentially expressed proteins and upstream regulators of cellular function. Comparison of biological processes of exosome-treated vs saline-treated LCA ligated hearts showed suppression of fibrosis and interstitial fibrosis along with fibrogenesis. There exist differential regulation of transcription factors that govern fibrotic processes. There was an intense expression of IL-1b and activation of pro-fibrotic signals in the saline-treated ischemia hearts and their suppression in MSC exosome-treated hearts. The results of proteomic studies were concordant with the limitation of fibrosis and inflammatory modulators in the exosome-treated hearts. To our knowledge, this is the first report on the early molecular events deciphering the molecular and proteomics events to explain MSC exosome-mediated suppression of scar formation in the ischemic mouse hearts. Conclusions MSC exosome treatment significantly reduced interstitial fibrosis in chronic ischemic hearts suggesting that they promote pro-regenerative cardiac ECM remodeling, in both infarct and peri-infarct areas by suppressing fibronectin secretion and by modulating collagen secretion to reduce fibrotic scar formation through altered cellular signaling pathways.

Impact of resolvin mediators in the immunopathology of diabetes and wound healing

ABSTRACT Introduction: Wound healing in diabetes may be delayed by persistent wound infection due to deficient immune and cellular response to tissue injury. Hyperglycemia due to decreased insulin availability and increased insulin resistance affects the immune response of the body. Accumulation of inflammatory immune cells and pro-inflammatory cytokines results in chronic inflammation and an altered resolution and remodeling phase of wound healing. Areas covered: Pro-resolving mediators called ‘resolvins’ target the resolution phase of wound healing and are becoming an area of increased interest. Resolvins stimulate self-limited innate immune responses and enhance innate microbial killing and clearance. Resolvins resolve inflammation by decreasing neutrophil infiltration and transmigration, increasing the phagocytic activity of macrophages, decreasing adipose tissue macrophages, downregulating platelet activation, suppressing nuclear factor-kappa beta activation, promoting the apoptosis of polymorphonuclear leukocytes, and improving insulin sensitivity. This review discusses the role of resolvins in diabetic wound healing and potential therapeutic strategies. The review is based on a literature search of PubMed and the Web of Science restricted to publications between January 2001 and October 2020. Expert opinion: There is increasing support for the use of resolvins in clinical applications related to diabetes and wound healing. Further research will help clarify this potential.

THE SIMULATION OF MECHANICAL STIMULATION EFFECT ON BONE ELASTICITY LIMIT BASED ON FINITE ELEMENT METHOD (FEM)

Osteoporosis is a disease affecting bones which is characterized by decreased bone density; bones become porous and susceptible to fractures. Osteoporosis occurs because of an imbalance during bone remodeling phase between resorption and formation processes. This study aims to simulate the effects of mechanical stimulations on the femoral bone elasticity limit. It is hoped that these mechanical stimuli can provide information on bone elasticity limits. Initially, we constructed the femur in two layers using triangular elements. Then we entered the bone properties (Young’s modulus and Poisson’s ratio) based on the age of the femur. After that we calculated the value of the stress, strain, and strain rate in the reversal phase. Next, we calculated the bone density using the thermodynamic equation and calculation of the bone elasticity limit using particle swarm optimization (PSO) methods. The value of stress and strain caused by walking is higher than the value of stress and strain when standing still. In this case, the difference in activity results an increase in stress by 33.82% and an increase in strain and strain rate by 34.57%. Based on these simulation results, it can be concluded that mechanical stimulation can increase the limit of bone elasticity to 2.99% in cortical bone and 0.975% in trabecular bone. Bone elasticity limit can be used to determine the level of osteoporosis that occurs. The higher value of the bone elasticity, the smaller the possibility of osteoporosis.