Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

Introduction: We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS.

Terpolymer-chitosan membranes as biomaterial.

The present study shows a novel copolymer synthesis, its application in the membrane design and the physicochemical and biological characterization of the biomaterial obtained. Terpolymer starting diisopropyl fumarate (F), vinyl benzoate (V) and 2-hydroxyethyl methacrylate (H) was prepared by thermal radical polymerization. This polymer (FVH) was obtained in several monomer ratios and characterized by spectroscopic and chromatographic methods (FTIR, H-NMR and SEC).

Design and characterization of microspheres for a 3D mesenchymal stem cell culture.

Recent studies have shown the relevance of growing mesenchymal stem cells (MSCs) in three-dimensional environments with respect to the monolayer cell culture on an adherent substrate. In this sense, macroporous scaffolds and hydrogels have been used as three-dimensional (3D) supports. In this work, we explored the culture of MSCs in a 3D environment created by microspheres, prepared with a fumarate-vinyl acetate copolymer and chitosan.

Nanobiocomposite based on natural polyelectrolytes for bone regeneration.

We developed a composite hydrogel based on chitosan and carboxymethyl cellulose with nanometric hydroxyapatite (nHA) as filler (ranging from 0.5 to 5%), by ultrasonic methodology to be used for bone regeneration. The 3D porous-structure of the biocomposite scaffolds were confirmed by Scanning Electron Microscopy and Microtomography analysis.

A cell-free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model.

The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for the differentiation of the mesenchymal stem cells that migrate from the bone marrow. The possible inflammatory response to these biomaterials was previously studied by means of the culture of RAW264.

Multi-Scale Approach for the Evaluation of Bone Mineralization in Strontium Ranelate-Treated Diabetic Rats.

Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics.

Advanced glycation end products and strontium ranelate promote osteogenic differentiation of vascular smooth muscle cells in vitro: Preventive role of vitamin D.

Advanced glycation end products (AGE) have been demonstrated to induce the osteogenic trans-differentiation of vascular smooth muscle cells (VSMC). Strontium ranelate (SR) is an anti-osteoporotic agent that has both anti-catabolic and anabolic actions on bone tissue. However, in the last years SR has been associated with an increase of cardiovascular risk.

Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

Aims: Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture.

Methods: 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM).

Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells.

Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats.

Novel Vanadium-Loaded Ordered Collagen Scaffold Promotes Osteochondral Differentiation of Bone Marrow Progenitor Cells.

Bone and cartilage regeneration can be improved by designing a functionalized biomaterial that includes bioactive drugs in a biocompatible and biodegradable scaffold. Based on our previous studies, we designed a vanadium-loaded collagen scaffold for osteochondral tissue engineering. Collagen-vanadium loaded scaffolds were characterized by SEM, FTIR, and permeability studies.

Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy.

Patients with long-term type 1 and type 2 diabetes mellitus (DM) can develop skeletal complications or "diabetic osteopathy". These include osteopenia, osteoporosis and an increased incidence of low-stress fractures. In this context, it is important to evaluate whether current anti-diabetic treatments can secondarily affect bone metabolism.

Ultrasonic compatibilization of polyelectrolyte complex based on polysaccharides for biomedical applications.

In recent years, there has been an increasing interest in the design of biomaterials for cartilage tissue engineering. This type of materials must meet several requirements. In this study, we apply ultrasound to prepare a compatibilized blend of polyelectrolyte complexes (PEC) based on carboxymethyl cellulose (CMC) and chitosan (CHI), in order to improve stability and mechanical properties through the inter-polymer macroradicals coupling produced by sonochemical reaction.

Effects of a metabolic syndrome induced by a fructose-rich diet on bone metabolism in rats.

Objective: The aims of this study were: first, to evaluate the possible effects of a fructose rich diet (FRD)-induced metabolic syndrome (MS) on different aspects of long bone histomorphometry in young male rats; second, to investigate the effects of this diet on bone tissue regeneration; and third, to correlate these morphometric alterations with changes in the osteogenic/adipogenic potential and expression of specific transcription factors, of marrow stromal cells (MSC) isolated from rats with fructose-induced MS.

Materials/methods: MS was induced in rats by treatment with a FRD for 28 days. Halfway through treatment, a parietal wound was made and bone healing was evaluated 14 days later.

Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: preventive effects of metformin.

Aims: Diabetes mellitus is associated with metabolic bone disease and increased low-impact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved.

Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation.

Accumulation of advanced glycation endproducts (AGEs) in bone tissue occurs in ageing and in Diabetes mellitus, and is partly responsible for the increased risk of low-stress bone fractures observed in these conditions. In this study we evaluated whether the anti-osteoporotic agent strontium ranelate can prevent the deleterious effects of AGEs on bone cells, and possible mechanisms of action involved. Using mouse MC3T3E1 osteoblastic cells in culture we evaluated the effects of 0.

Morphological changes induced by advanced glycation endproducts in osteoblastic cells: effects of co-incubation with alendronate.

Advanced glycation endproducts (AGEs) accumulate with age in various tissues, and are further increased in patients with Diabetes mellitus, in which they are believed to contribute to the development and progression of chronic complications that include a decrease in bone quality. Bisphosphonates are anti-osteoporotic drugs that have been used for the treatment of patients with diabetic bone alterations, although with contradictory results. In the present study, we have evaluated the in vitro alterations on osteoblastic morphology by environmental scanning electron microscopy, in actin cytoskeleton and apoptosis induced by AGEs, as well as the modulation of these effects by alendronate (an N-containing bisphosphonate).

Chlorhexidine delivery system from titanium/polybenzyl acrylate coating: evaluation of cytotoxicity and early bacterial adhesion.

Objectives: The formation of biofilms on titanium dental implants is one of the main causes of failure of these devices. Streptococci are considered early colonizers that alter local environment favouring growing conditions for other colonizers. Chlorhexidine (CHX) is so far the most effective antimicrobial treatment against a wide variety of Gram-positive and Gram-negative organisms as well as fungi.

Metformin prevents anti-osteogenic in vivo and ex vivo effects of rosiglitazone in rats.

Long-term treatment with the insulin-sensitizer rosiglitazone reduces bone mass and increases fracture risk. We have recently shown that orally administered metformin stimulates bone reossification and increases the osteogenic potential of bone marrow progenitor cells (BMPC). In the present study we investigated the effect of a 2-week metformin and/or rosiglitazone treatment on bone repair, trabecular bone microarchitecture and BMPC osteogenic potential, in young male Sprague-Dawley rats.

Development of an osteoconductive PCL-PDIPF-hydroxyapatite composite scaffold for bone tissue engineering.

Hydroxyapatite (HAP)-containing poly-ε-caprolactone (PCL)-polydiisopropyl fumarate (PDIPF) composite (Blend) was developed as an alternative for bone tissue engineering. The physicochemical, mechanical and biocompatibility properties of these composites were evaluated using two osteoblast-like cell lines (UMR106 and MC3T3E1) and compared with the blend without HAP and PCL/HAP films. The increment in the elastic modulus and the decrease in the elongation-at-break of Blend-HAP suggest that the mechanical properties of the HAP scaffolds have improved significantly.

Characterization of poly(epsilon-caprolactone)/polyfumarate blends as scaffolds for bone tissue engineering.

There is considerable interest in the design of polymeric biomaterials that can be used for the repair of bone defects. In this study, we used ultrasound to prepare a compatibilized blend of poly(epsilon-caprolactone) (PCL) and poly(diisopropyl fumarate) (PDIPF). The formation of post-sonication inter-polymer coupling products was verified by SEC analysis of a blend with azo-labeled PDIPF.

Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies.

Diabetes mellitus is associated with bone loss. Patients with type 2 diabetes are frequently treated with oral antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones. Rosiglitazone treatment has been shown to increase adipogenesis in bone marrow and to induce bone loss.