Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model.

Current strategies in implant technology are directed to generate bioactive implants that are capable to activate the regenerative potential of the surrounding tissue. On the other hand, implant-related infections are a common problem in orthopaedic trauma patients. To meet both challenges, i.

A dual function of copper in designing regenerative implants.

The supply of titanium implants which are widely used in orthopaedics with both regenerative and anti-microbial properties will achieve a great progress in bone regeneration. We asked, whether by appropriate concentrations of copper ions it will be possible both to inhibit growth of bacteria and stimulate biological responses in mesenchymal stem cells (MSC). Using titanium material which released galvanically deposited copper at concentrations from 0.

Guidance of mesenchymal stem cells on fibronectin structured hydrogel films.

Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface.

Long-term tumor necrosis factor treatment induces NFκB activation and proliferation, but not osteoblastic differentiation of adipose tissue-derived mesenchymal stem cells in vitro.

The pro-inflammatory cytokine tumor necrosis factor (TNF) is well known to induce differentiation of bone matrix-resorbing osteoclasts from hematopoietic stem cells. However, the impact of TNF on differentiation of bone matrix-forming osteoblasts from mesenchymal stem cells (MSC) was only fragmentarily studied so far. Therefore, we investigated what impact long-term TNF treatment has on osteoblastic differentiation of MSC isolated from the adipose tissue (ASC) in vitro.

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro.

Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands.

Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro.

Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors.

Modulating the actin cytoskeleton affects mechanically induced signal transduction and differentiation in mesenchymal stem cells.

Mechanical interactions of mesenchymal stem cells (MSC) with the environment play a significant role in controlling the diverse biological functions of these cells. Mechanical forces are transduced by integrins to the actin cytoskeleton that functions as a scaffold to switch mechanical signals into biochemical pathways. To explore the significance of cytoskeletal mechanisms in human MSC we modulated the actin cytoskeleton using the depolymerising drugs cytochalasin D (CytD) and latrunculin A (LatA), as well as the stabilizing drug jasplakinolide (Jasp) and examined the activation of the signalling molecules ERK and AKT during mechanical loading.

Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds.

The interaction of mesenchymal stem cells (MSCs) with endothelium in vivo is significant for regenerative processes in organisms. To design concepts for tissue engineering for bone regeneration based on this interaction, the osteogenic differentiation of human bone marrow-derived MSCs in a co-culture with human dermal microvascular endothelial cells (HDMECs) was studied. The experiments were focussed on the regulation of MSCs in a co-culture with HDMECs on different calcium phosphate scaffolds.

Interface biology of implants.

To successfully apply implant materials for regenerative processes in the body, understanding the mechanisms at the interface between cells or tissues and the artificial material is of critical importance. This topic is becoming increasing relevant for clinical applications. For the fourth time, around 200 scientists met in Rostock, Germany for the international symposium "Interface Biology of Implants".

Time-dependent adhesive interaction of osteoblastic cells with polished titanium alloyed implant surfaces.

Aim: Design optimization and surface modifications of orthopedic implants are focused on adhesive properties depending on specific applications. To obtain an in-vitro understanding of the adhesion interaction of bone cells on implant surfaces the time-dependent adhesion behavior of osteoblastic cells was studied.

Materials And Methods: MG-63 osteoblastic cells were seeded on discs of polished titanium alloy (Ti6Al4V) and allowed to adhere for various time periods (1 to 48 h).

Albumin-binding capacity (ABiC) is reduced in patients with chronic kidney disease along with an accumulation of protein-bound uraemic toxins.

Background: Albumin is an important transport protein for non-water-soluble protein-bound drugs and uraemic toxins. Its transport capacity is reduced in patients with advanced chronic kidney disease (CKD) and unbound fractions of uraemic toxins are related to complications of CKD. We investigated whether this reduction could be quantified and how it correlated with the stages of CKD.

Mechanical integrin stress and magnetic forces induce biological responses in mesenchymal stem cells which depend on environmental factors.

The control of mesenchymal stem cells (MSC) by physical cues is of great interest in regenerative medicine. Because integrin receptors function as mechanotransducers, we applied drag forces to β1 integrins on the apical surface of adherent human MSC. In addition to mechanical forces, the technique we used involved also the exposure of the cells to an inhomogeneous magnetic field.

Changes in human endothelial cell energy metabolic capacities during in vitro cultivation. The role of "aerobic glycolysis" and proliferation.

Background: In this study the influence of cultivation and proliferation on energy metabolic characteristics of human umbilical vein endothelial cells (HUVEC) has been examined. The energy metabolic capacities of human endothelial cells freshly isolated from the umbilical vein were compared with those after cultivation for three passages and as subconfluent and confluent cultures.

Methods: Expression of cell type-specific differentiation markers and proliferative activity were studied in dependency on cultivation characteristics.

Interface biology of implants.

Implants are widely used in various clinical disciplines to replace or stabilize organs. The challenge for the future is to apply implant materials to specifically control the biology of the surrounding tissue for repair and regeneration. This field of research is highly interdisciplinary and combines scientists from technical and life sciences disciplines.

Morphometric immunohistochemical examination of the inflammatory tissue reaction after implantation of calcium phosphate-coated titanium plates in rats.

Calcium phosphate (CaP) preparations are established coatings for titanium-based medical implants used for bone reconstruction. However, biodegradation of the coating can result in microparticles that subsequently cause inflammatory reactions. The present study was therefore aimed at investigating the inflammatory response to two series of CaP-coated titanium plates: Ti-brushite (Ti-B) and Ti-hydroxyapatite (Ti-H) implants.

Calcium phosphate surfaces promote osteogenic differentiation of mesenchymal stem cells.

Although studies in vivo revealed promising results in bone regeneration after implantation of scaffolds together with osteogenic progenitor cells, basic questions remain how material surfaces control the biology of mesenchymal stem cells (MSC). We used human MSC derived from bone marrow and studied the osteogenic differentiation on calcium phosphate surfaces. In osteogenic differentiation medium MSC differentiated to osteoblasts on hydroxyapatite and BONITmatrix, a degradable xerogel composite, within 14 days.

Influence of manganese ions on cellular behavior of human osteoblasts in vitro.

Divalent cations like Mn(2+) are known to strongly influence the integrin affinity to ligands and - in consequence - cell adhesion to extracellular matrix proteins. Therefore, divalent cation supplementation of biomaterials could be a promising approach to improve the ingrowth and the integration of implants. We were interested, whether manganese ions affect cellular functions like spreading, proliferation as well as gene expression in human osteoblasts.

Improved initial osteoblast functions on amino-functionalized titanium surfaces.

Adhesion and spreading of cells on biomaterials are integrin-mediated processes. But recent findings indicate a key role of the cell membrane associated matrix substance hyaluronan (HA) in interface interactions. Because HA is a negatively charged molecule we assume that a biomaterial surface with an opposed charge could boost the first contact of the cell to the surface.

Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials.

The survival and functioning of a bone biomaterial requires a rapid and stable vascularization after implantation. However, the mechanisms involved in the context of the complex healing microenvironment are poorly understood. To evaluate the vascularization potential of bone biomaterials, angiogenic stimuli were added to human dermal microvascular endothelial cells (HDMEC) growing on three-dimensional (3-D) bone biomaterials consisting of porous hydroxyapatite, porous calcium phosphate, porous nickel-titanium, successfully being used in humans, and also silk fibroin nets.

Therapeutic strategies in autoimmune diseases by interfering with leukocyte endothelium interaction.

The interaction of leukocytes with the vessel endothelium to facilitate the extravasation into the tissue represents a key process of the body's defense mechanisms. Excessive recruitment of leukocytes into the inflamed tissue in chronic diseases like autoimmune disorders could be prevented by interfering with the mechanisms of leukocyte extravasation. Significant progress in elucidating the molecular basis of the trafficking of leukocytes from the blood stream to the extravascular tissue has been achieved that enables new strategies for therapeutic approaches.

The influence of surface roughness of titanium on beta1- and beta3-integrin adhesion and the organization of fibronectin in human osteoblastic cells.

Mechanisms of cell adhesion and extracellular matrix formation are primary processes in the interaction with the material surface of an implant which are controlled by integrin receptors. The aim of our study was to find out whether beta1- and beta3-integrins of osteoblastic cells sense the surface topography of titanium, and if structural alterations of integrin adhesions were involved in the organization of fibronectin. Pure titanium surfaces were modified by polishing (P), machining (NT), blasting with glass spheres (GB), and blasting with corundum particles (CB) resulting in increasing roughness.

Cellular investigations on electrochemically deposited calcium phosphate composites.

Electrochemically deposited calcium phosphate (CaP) coatings are fast resorbable and existent only during the first period of osseointegration. In the present study, composite coatings with varying solubility (hydroxyapatite (HA), brushite with less HA and monetite (M) with less HA) were prepared and the influence of the degradation and the reprecipitation of CaP on osteoblastic cells were investigated. On the brushite composite coating a new precipitated, finely structured CaP phase was observed during immersion in cell culture medium with or without osteoblastic cells.

Control of focal adhesion dynamics by material surface characteristics.

The mechanisms of cell adhesion to the extracellular matrix (ECM) which are of fundamental importance for function, survival, and growth of cells involve the formation of focal adhesions to facilitate integrin signaling. Recently, it became evident that focal adhesions are not stable but move to enable cell migration and ECM formation. We examined the number, size, and dynamic behavior of focal adhesions in living MG-63 osteoblastic cells, which were cultured on titanium surfaces with different roughnesses and on stainless steel (SS).

Induction of apoptosis by the calcium antagonist mibefradil correlates with depolarization of the membrane potential and decreased integrin expression in human lens epithelial cells.

Background: Posterior capsule opacification is still the major complication in cataract surgery and is caused by migration and proliferation of residual lens epithelial cells. The challenge of a suitable therapy to inhibit capsule opacification is to specifically interfere with cellular mechanisms. Our approach using the T-calcium channel antagonist mibefradil is based on the hypothesis that this drug inhibits the signaling pathways mediated by cell adhesion.

Impaired mechanisms of leukocyte adhesion in vitro by the calcium channel antagonist mibefradil.

Purpose: Enhanced adhesion to the vascular endothelium and excessive trafficking to extravascular locations can lead to serious tissue injury and destruction. Therefore, interfering with molecular mechanisms of leukocyte adhesion to the vascular endothelium is an important goal to block diseases like chronic inflammations and atherosclerosis.

Methods: We studied the influence of the calcium antagonists mibefradil (T-type channel blocker), amlodipine and verapamil (both L-type channel blockers) on mechanisms related to leukocyte adhesion using isolated peripheral human blood leukocytes.