No abstract

Diabetes mellitus, a complex metabolic disorder, leads to many health complications like kidney failure, diabetic heart disease, stroke, and foot ulcers. Treatment approaches of diabetes and identification of the mechanisms underlying diabetic complications of the skin have gained importance due to continued rapid increase in the diabetes incidence. A thick and pre-vascularized in vitro 3D type 2 diabetic human skin model (DHSM) was developed in this study. The methacrylated gelatin (GelMA) hydrogel was produced by photocrosslinking and its pore size (54.85 ± 8.58 μm), compressive modulus (4.53 ± 0.67 kPa) and swelling ratio (17.5 ± 2.2%) were found to be suitable for skin tissue engineering. 8% GelMA hydrogel effectively supported the viability, spreading and proliferation of human dermal fibroblasts. By isolating dermal fibroblasts, human umbilical vein endothelial cells and keratinocytes from type 2 diabetic patients, an in vitro 3D type 2 DHSM, 12 mm in width and 1.86 mm thick, was constructed. The skin model consisted of a continuous basal epidermal layer and a dermal layer with blood capillary-like structures, ideal for evaluating the effects of anti-diabetic drugs and wound healing materials and factors. The functionality of the DHSM was showed by applying a therapeutic hydrogel into its central wound; especially fibroblast migration to the wound site was evident in 9 d. We have demonstrated that DHSM is a biologically relevant model with sensitivity and predictability in evaluating the diabetic wound healing potential of a therapeutic material.

Despite the fast development of technology in the world, diabetic foot wounds cause deaths and massive economical losses. Diabetes comes first among the reasons of non traumatic foot amputations. To reduce the healing time of these fast progressing wounds, effective wound dressings are in high demand. In our study, sheep small intestinal submucosa (SIS) based biocompatible sponges were prepared after SIS decellularization and their wound healing potential was investigated on full thickness skin defects in a diabetic rat model. The decellularized SIS membranes had no cytotoxic effects on human fibroblasts and supported capillary formation by HUVECs in a fibroblast-HUVEC co-culture. Glutaraldehyde crosslinked sponges of three different compositions were prepared to test in a diabetic rat model: gelatin (GS), gelatin: hyaluronic acid (GS:HA) and gelatin: hyaluronic acid: SIS (GS:HA:SIS). The GS:HA:SIS sponges underwent a 24.8 ± 5.4% weight loss in a 7-day in vitro erosion test. All sponges had a similar Young’s modulus under compression but GS:HA:SIS had the highest (5.00 ± 0.04 kPa). Statistical analyses of histopathological results of a 12-day in vivo experiment revealed no significant difference among the control, GS, GS:HA, and GS:HA:SIS transplanted groups in terms of granulation tissue thickness, collagen deposition, capillary vessel formation, and foreign body reaction (P > 0.05). On the other hand, in the GS:HA:SIS transplanted group 80% of the animals had a complete epidermal regeneration and this was significantly different than the control group (30%, P < 0.05). Preclinical studies revealed that the ECM of sheep small intestinal submucosa can be used as an effective biomaterial in diabetic wound healing.

Düşük seviyeli lazer terapisi, rejeneratif tıpta fonksiyonel anomalilerin yönetilmesi, iyileşme sürecini ve hücresel fonksiyonları geliştirmek için düşük seviyeli lazerlerin kullanıldığı bir tedavi yaklaşımıdır. Çalışmada, bu tedavi yaklaşımının diyabetik hastalarda rastlanan en önemli problemlerden birisi olan diyabetik yaraların iyileşmesinde etkinliğinin araştırılması amaçlanmıştır. Yöntem: İnsan derisinden izole edilmiş olan Tip 2 diyabetik ve normoglisemik insan dermal fibroblast hücrelerine belirli sürelerde (10-100 saniye) iki günde bir, 9 gün süresince 980 nm dalga boyundaki diyot lazer uygulanmış ve hücre sayıları ve sentezlenen Tip 1 kollajen miktarları karşılaştırılmıştır. Bulgular: Her iki hücre tipinde de uygulanan sürelerdeki lazerin hücreler üzerinde herhangi bir sitotoksik etkiye yol açmadığı, ancak hücrelere 50 sn.'den fazla uygulanmasının anlamlı düzeyde hücre çoğalmasını yavaşlattığı tespit edilmiştir. Hücrelerde sentezlenen kollajen miktarları kıyaslandığında normoglisemik hücrelerde daha fazla sentez olduğu sonucuna varıldı. Tip 2 diyabetik insan dermal fibroblast hücrelerinde en yüksek kollajen sentezine 90 sn. lazer uygulaması sonucunda rastlanırken normoglisemik hücrelerde en yüksek kollajen sentezine 70 sn. lazer uygulamasında ulaşıldı. Sonuç: Diyot lazerin olumlu etkilerinin görülmesinde uygulama sürelerinin hücre tipine göre değiştiği, hasta profiline göre uygun sürelerde uygulanan lazerin düşük maliyetle, hastaya en az zararla, hastadaki yara iyileşme sürecini olumlu yönde etkileyebileceği düşünülmektedir.

Aim: Gestational diabetes mellitus (GDM) is associated with an increased risk of fetal and maternal complications, such as type 2 DM and cardiovascular disease (CVD). This study aimed to predict the potential for future vascular complications in mothers with GDM by evaluating oxidative stress, endothelial NO synthase (eNOS) expression and vascular smooth muscle cell (VSMC) proliferation in the umbilical vessels of mothers with GDM. Material and Methods: Subjects were divided into two groups: normoglycemic control (NGC) group (n = 10) and GDM group (n = 12). Expression of eNOS and production of reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs) were determined. The mitochondrial mass of HUVECs was evaluated by spectrofluorometry. VSMC proliferation was ascertained in vitro with an EdU cell proliferation assay. Advanced glycation end products (AGEs) accumulation was measured by ELISA and assessed by immunohistochemical staining. Results: VSMC proliferation, eNOS expression, and ROS production in HUVECs were significantly increased, and greater immunohistochemical staining to AGEs was observed in endothelium in GDM. Conclusion: Increased oxidative stress, which elevates eNOS expression and VSMC proliferation in the umbilical vessels of mothers with GDM, may be a sign that mothers have a high potential for developing diabetes or cardiovascular disease in the future.