A Self-Powered Piezo-Bioelectric Device Regulates Tendon Repair-Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels.

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes. Here, the dynamic response of tendon cells to a piezoelectric collagen-analogue scaffold comprised of aligned nanoscale fibers made of the ferroelectric material poly(vinylidene fluoride-co-trifluoroethylene) is shown. It is demonstrated that motion-powered electromechanical stimulation of tendon tissue through piezo-bioelectric device results in ion channel modulation in vitro and regulates specific tissue regeneration signaling pathways. Finally, the potential of the piezo-bioelectronic device in modulating the progression of tendinopathy-associated processes in vivo, using a rat Achilles acute injury model is shown. This study indicates that electromechanical stimulation regulates mechanosensitive ion channel sensitivity and promotes tendon-specific over non-tenogenic tissue repair processes.

Effects of cell-mediated osteoprotegerin gene transfer and mesenchymal stem cell applications on orthodontically induced root resorption of rat teeth.

Aim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). Materials and methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100g of orthodontic force was applied to upper first molar teeth of rats for 14 days. MSCs and transfected MSC injections were performed at 1st, 6th, and 11th days to the MSC and GT group rats. At the end of experiment, upper first molar teeth were prepared for genetical, scanning electron microscopy (SEM), fluorescent microscopy, and haematoxylin eosin-tartrate resistant acid phosphatase staining histological analyses. Number of total cells, number of osteoclastic cells, number of resorption lacunae, resorption area ratio, SEM resorption ratio, OPG, RANKL, Cox-2 gene expression levels at the periodontal ligament (PDL) were calculated. Paired t-test, Kruskal-Wallis, and chi-square tests were performed. Results: Transferred MSCs showed marked fluorescence in PDL. The results revealed that number of osteoclastic cells, resorption lacunae, resorption area ratio, RANKL, and Cox-2 were reduced after single MSC injections significantly (P < 0.05). GT group showed the lowest number of osteoclastic cells (P < 0.01), number of resorption lacunae, resorption area ratio, and highest OPG expression (P < 0.001). Conclusions: Taken together all these results, MSCs and GT showed marked inhibition and/or repair effects on OIIRR during orthodontic treatment on rats.

Changes in the inflammatory markers with advancing stages of diabetic nephropathy and the role of pentraxin-3.

BACKGROUND: Immunological and inflammatory mechanisms have been shown to have role in both the development and progression of diabetic nephropathy (DNP). There is need for more specific markers for inflammation as the ones commonly used are influenced by many factors. Pentraxin-3 (PTX-3) seems to be a potential candidate. We aimed in our study to evaluate the changes of PTX-3 levels in different stages of DNP and its relationship with other inflammatory markers. METHODS: This is a cross sectional study in which patients with DNP at different stages were involved. Patient were divided into three groups according to estimated glomerular filtration rate (eGFR), microalbuminuria and proteinuria levels: Group-1: eGFR >60 mL/min and microalbuminuria, Group-2: eGFR >60 mL/min and macroalbuminuria, Group-3: eGFR <60 mL/min and macroalbuminuria. Besides the routine biochemical parameters, levels of PTX-3, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1 and tumor necrosis factor (TNF)-α was measured. Groups were compared with each other regarding the study parameters and correlation of PTX-3 with other markers was evaluated. RESULTS: The mean PTX-3 level in Group-2 (0.94 ± 0.26 ng/mL) and -3 (1.35 ± 1.55 ng/mL) were higher than in Group-1 (0.81 ± 0.25 ng/mL) (p = 0.009 and p = 0.012). There was a significant correlation of PTX-3 with proteinuria (r = 0.266, p = 0.016), microalbuminuria (r = 0.304, p = 0.014) and hypoalbuminemia (r = 0.197, p = 0.043). PTX-3 was not correlated with other markers of inflammation (IL-1, TNF-α and hsCRP) and diabetic metabolic parameters (hbA1c, C-peptide, insulin and HOMA-IR). PTX-3, IL-1 and TNF-α levels increased with the advancing stage of DNP while hsCRP level did not change. CONCLUSION: PTX-3 that increases similar to other markers of inflammation (IL-1, TNF-α) is a better inflammatory marker than hsCRP. Furthermore, there is a relationship between PTX-3 and proteinuria independent from eGFR.

A case of newly diagnosed klippel trenaunay weber syndrome presenting with nephrotic syndrome.

Klippel Trenaunay Weber syndrome (KTWS) is a rare disease characterized by hemihypertrophy, variceal enlargement of the veins, and arteriovenous (AV) malformations. Renal involvement in KTWS is not known except in rare case reports. Herein, we present a case of KTWS with nephrotic syndrome. A 52-year-old male was admitted due to dyspnea and swelling of the body for the last three months. The pathological physical findings were diffuse edema, decreased lung sounds at the right basal site, increased diameter and decreased length of the left leg compared with the right one, diffuse variceal enlargements, and a few hemangiomatous lesions on the left leg. The pathological laboratory findings were hypoalbuminemia, hyperlipidemia, increased creatinine level (1.23 mg/dL), and proteinuria (7.6 g/day). Radiographic pathological findings were cystic lesions in the liver, spleen, and kidneys, splenomegaly, AV malformation on the left posterolateral thigh, and hypertrophy of the soft tissues of the proximal left leg. He was diagnosed to have KTWS with these findings. Renal biopsy was performed to determine the cause of nephrotic syndrome. The pathologic examination was consistent with focal segmental sclerosis (FSGS). He was started on oral methylprednisolone at the dosage of 1 mg/kg and began to be followedup in the nephrology outpatient clinic.