Markus Laub

• Dr.
• University of Duisburg-Essen

This study compared the osseointegration of acid-etched, ultrahydrophilic, micro- and nanostructured implant surfaces (ANU) with non-ultra-hydrophilic, microstructured (SA) and non-ultrahydrophilic, micro- and nanostructured implant surfaces (AN) in vivo. Fifty-four implants (n = 18 per group) were bilaterally inserted into the proximal tibia of Ne...

A process for the production of a storable implant with aqueous an ultrahydrophilic surface, the process comprising the steps of: providing an implant with an ultrahydrophilic surface, said ultrahydrophilic surface comprising a metal, metallic alloy, or ceramic material with dynamic contact angles from 0° to 10° upon wetting of the surface of the i...

Aim Obstructive Sleep Apnoea (OSA) is frequent in patients with type 2 diabetes. The aim of this study is to evaluate prevalence of OSA in patients with type 1 diabetes. Methods In a cross-sectional design, all patients with type 1 diabetes attending the outpatient clinic were offered screening for OSA for one night with the ApneaLink + home-monit...

Ultrahydrophilic titanium miniplates with sandblasted and acid etched (SLA) surfaces were protected from loss of hydrophilicity by an exsiccation layer of salt and stored in a dry state. Various salts in different concentrations were tested in respect to their conservation capacity and optical appearance. Potassium phosphate buffer in a specified c...

The objective of the present work is to fabricate and develop growth factor-PDLLA nano-composites by electrospinning into 2D fleece or 3D tubular scaffolds that can mimic the nature and function of the native extracellular matrix of bone tissue or artificial blood vessels. The bioactive growth factors 125 I-rhVEGF 165 , 125 I-rhBMP-2 and the fibrou...

Electro spun PDLLA-nanofibers were functionalized with 125 I-rhBMP-2 and 125 I-rhVEGF165, either by protein-adsorption to, or by incorporation into electrospun PDLLA-nanofibers. Both, adsorbed and incorporated growth factors could be visualized via autoradiography. By fitting the release data according the two phase exponential decay, release rates...

For the successful regeneration of lost bone, the use of biomaterial-based substitutes in combination with factors that promote the regenerative process, such as vascular endothelial growth factor (VEGF) or bone morphogenetic protein 2 (BMP-2), might be promising. In this study, a model was used which generated capillary-like vessels by co-cultivat...

Two methods of contact angle measurement are applied on screw type dental implants composed of titanium with different surfaces: The standard Wilhelmy method (dynamic measurement) and an extended sessile drop method (static measurement), where droplets with a volume in the picoliter range are generated. Both methods lead to comparable but in detail...

AimsTo investigate the prevalence of symptomatic obstructive sleep apnoea in unselected patients with Type 2 diabetes referred to a tertiary diabetes clinic.Methods In a cross-sectional design, all newly referred patients were offered a stepwise screening for obstructive sleep apnoea with: (1) The Berlin questionnaire; then, if indicative: (2) over...

Sandblasted titanium screw type implants were acid-etched by two different methods using a semiautomatic wet chemical processing platform. Both etching methods led to homogenous, micro-structured and hyperhydrophilic surfaces making them especially suitable for dental applications. However processing time and procedural complexity differ greatly be...

Composite tablets of human recombinant bone morphogenetic protein 2 (rhBMP-2) and poly-(D,L)-lactide (PDLLA) (1-2 mg rhBMP-2/g PDLLA) were prepared by foaming of PDLLA with supercritical CO 2. Release kinetics of rhBMP-2 were measured by a continuous flow and a batch dilution method at 22°C and 50 °C respectively. In both cases a two-phase first-or...

The assembly and stability of polyelectrolyte multilayers (PEMs) was studied with the tracer 125 I-Poly-L-lysine together with chondroitin sulphate on microstructured titanium surfaces (µSLA). PEM assembly followed an exponential growth curve, which is mimicked by rhBMP-2 binding on glass slides during assembly. PEM disassembly occurred with a half...

Recently imaginary contact angles were introduced to monitor hydrophilicitiy beyond a contact angle of zero degrees. This discovery has never been systematically applied to a defi ned surface. Therefore, a batch of 30 ultrahydrophilic titanium miniplates (θ ≤ 10°, no hysteresis), prepared by sand-blasting with large grit and acid etching (SLA), was...

Angiogenesis and osteogenesis are closely related processes sharing some essential mediators like VEGF (Vascular Endothelial Growth Factor) and BMP-2 (Bone Morphogenetic Protein-2). As vascularization is crucial to bone formation biofunctionalization of bone replacement materials with both of these proteins may result in enhanced bone formation. He...

With acid hydrophilized rough titanium plasma sprayed (TPS) miniplates (10.4 x 5.2 x 1.7 mm; Ra = 22 With acid hydrophilized rough titanium plasma sprayed (TPS) miniplates (10.4 x 5.2 x 1.7 mm; Ra = 22 μm; rm = 8) we discovered that ca. 20% of the data in each Wilhelmy balance measurement corresponded to "forbidden" data of the type cos θ > 1.0. It...

The main objectives of the study described below were of two-fold nature: (1) to examine if rhBMP-2-biocoated implants in a pig model could lead to ectopic bone formation and (2) if quantitative and/or qualitative differences could be found between adhesively and covalently bonded BMP II using the scintigraphic method. In order to examine these cen...

A functionalization is required for calcium phosphate-based bone substitute materials to achieve an entire bone remodeling. In this study it was hypothesized that a tailored composite of tricalcium phosphate and a bioactive glass can be loaded sufficiently with rhBMP-2 for functionalization. A composite of 40 wt% tricalcium phosphate and 60 wt% bio...

The selective degradation of many proteins in eukaryotic cells is carried out by the ubiquitin system. In this pathway, proteins are targeted for degradation by covalent ligation to ubiquitin, a highly conserved protein [1]. Ubiquitylated proteins were degraded by the 26S proteasome in an ATP-depended manner. The degradation of ubiquitylated protei...

Kurzfassung In der Literatur werden zahlreiche Versuche beschrieben, die Bildung von neuem Knochen durch eine Kombination von Knochenersatzmaterialien mit BMP-2 zu steigern. Ein großes Problem in der chirurgischen Anwendung stellt jedoch die Wasserlöslichkeit des BMP-2 dar, die zu einer sehr schnellen Verteilung des Proteins im Körper führt. Die Fr...

Chicken eggs in the early phase of breeding are between in vitro and in vivo systems and provide a vascular test environment not only to study angiogenesis but also to study tumorigenesis. After the chick chorioallantoic membrane (CAM) has developed, its blood vessel network can be easily accessed, manipulated and observed and therefore provides an...

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor of the transforming growth factor-beta superfamily. Members of this protein family are involved in the development of various mammalian tissues, including the inner ear. As their notations indicate, they also have well-known effects on bone formation and regeneration. In th...

Nanoparticle (NP)-based delivery has gained importance for improving the potency of therapeutic agents. The bovine serum albumin (BSA) NPs, obtained by a coacervation process, was modified by electrostatic adsorption of cationic polyethylenimine (PEI) to NP surfaces for delivery of bone-inducing growth factor, bone morphogenetic protein-2 (BMP-2)....

The covalent and non-covalent immobilization of growth factors such as recombinant human bone morphogenetic protein 2 (rhBMP-2) on metals and bone replacement materials in bioactive form is a recent development. Up to now the immobilization technology usually involved the chemical modification and activation of the biomaterial surface followed by a...

On the basis of their osteoinductive properties bone morphogenetic proteins (BMPs) are used today in clinical therapy such as the treatment of spinal disorders or healing defects in tibia fractures. A major biochemical function of these molecules is their binding to a large number of other proteins to fulfil their biological role. Two of these BMP-...

The ultrahydrophilic surface is prepared in two steps: (i) Immersing the metal implant in chromosulphuric acid having a density of more than 1.40g/cm3 , at a temperature of above 200°C, for a period of from 10 to 90 minutes; and (ii) quenching the metal implant by immersion in concentrated sulphuric acid at a temperature of15° to 25° C. and washing...

The ultrahydrophilic surface is prepared in two steps: (i) Immersing the metal implant in chromosulphuric acid having a density of more than 1.40g/cm3 , at a temperature of above 200°C, for a period of from 10 to 90 minutes; and (ii) quenching the metal implant by immersion in concentrated sulphuric acid at a temperature of15° to 25° C. and washing...

The aim of the present study was to investigate bone formation to recombinant human bone morphogenetic protein-2 (rhBMP-2)-biocoated and rhBMP-2-nonbiocoated titanium implants after implantation in dogs. Implantation of sand-blasted and acid-etched (C), chromosulfuric acid surface-enhanced (CSA), and rhBMP-2-biocoated CSA [BMP-A: noncovalently immo...

The present invention is characterized by the findings that the use of amphiphilic tensides in the adsorption buffer , can improve the surface absorption characteristics of materials which serve as implant materials, made from metals, alloys, ceramic materials and combinations thereof. The "conformational Enhancer" (CHAPS: 3-[(3-Cholamidopropyl)-di...

Hydroxyapatite (HAP) has a great potential as a bone replacement material because of its similarity to the crystal structure of inorganic matrix of bone. Several years ago we showed that porous hydroxyapatite ceramics (Endobon, Merck) can be covalently modified for the immobilization of proteins [Jennissen, H.P. (1999) PCT Patent WO9926674A2] openi...

3D‐Rapid Prototyping (3D‐RP) is a novel technique for the construction of highly accurate three‐dimensional polyamide models of biomolecules. This method has been shown to be a valuable tool in the modeling of protein‐protein‐interactions as well as in the analysis of surface topography. Using this technique we were recently able to identify a so f...

A method is described for a specific adsorption (affinity-type) rhBMP-2 on an artifical helical structure via its binding to the helical groove (= antihelical structure) of rhBMP-2. The necessary computer for the calculation of the specific polypeptide helix simulations were not possible on the computers of that time. [1] Laub, M., Seul, T., Schma...

Recently we were able to apply the technique of 3D‐Rapid Prototyping (3D‐RP) to the construction of highly accurate three‐dimensional plastic models of biomolecules [Laub, M. et al. (2001), Materialwiss. Werkstofftech. 32, 926]. These models are derived from x‐ray crystallographic data and therefore represent exact replicas of the depicted molecule...

Bone morphogenetic proteins (BMPs) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Although recently recombinant human BMP-2 (rhBMP-2) has been chemically immobilized on implant surfaces leading to enhanced bone growth and acce...

Bone morphogenetic proteins (BMP) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Recently BMP-2 has been chemically immobilized on implant surfaces leading to enhanced bone growth and accelerated integration in sheep. Although...

Bone morphogenetic proteins (BMP) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Recently BMP-2 has been chemically immobilized on implant surfaces leading to enhanced bone growth and accelerated integration in sheep. Although...

Ubiquitin is often implicated as a specific tag for protein degradation via the ubiquitin system although only a limited number of physiological proteins have been shown to be degraded in their native tissues via this pathway in vivo. Ubiquitin may also, however, have other functions of a regulatory nature (non-catabolic ubiquitylation). The ubiqui...

Ubiquitin−calmodulin ligase (uCaM synthetase; EC6.3.2.21), which has been detected in all tissues so far examined, catalyzes the Ca2+-dependent reversible synthesis of ubiquityl-calmodulin which is not directed to degradation by the ATP-dependent 26-S protease [Laub, M. & Jennissen, H. P. (1997) Biochim. Biophys. Acta 1357, 173−191]. As has been sh...

Calmodulin is the universal calcium modulator in eukaryotic cells. Its biological activity is closely regulated by the second messenger Ca2+. Previous studies in cell-free extracts [Laub, M. & Jennissen, H. P. (1997) Biochim. Biophys. Acta 1357, 173-191] have shown that calmodulin is reversibly ubiquitylated by ubiquityl-calmodulin synthetase (ubiq...

Ubiquitin-calmodulin ligase (uCaM synthetase: EC 6.3.2.21), which has been detected in all tissues so far examined, catalyzes the Ca2+-dependent reversible synthesis of ubiquityl-calmodulin which is not directed to degradation by the ATP-dependent 26-S protease [Laub, M. & Jennissen, H. P. (1997) Biochim. Biophys. Acta 1357, 173-191]. As has been s...

Calmodulin is the natural substrate for ubiquitin-ligation by the enzyme ubiquitin-calmodulin ligase (uCaM-synthetase; EC 6.3.2.21). The activity of this ligase is regulated by the binding of the second messenger Ca2+ to the substrate calmodulin, which increases the activity ca. 10-fold. Up till now, two components of the ligase could be identified...

Mammalian ubiquityl-caimodulin synthetase (EC 6.3.2.21) covalently links up to five molecules ubiquitin to a single lysine residue in calmodulin building up a polyubiquitin- tail. Ubiquitylation appears to suppress the biological activity of calmodulin in the activation of phosphorylase kinase [1]. Attempts to show degradation of calmodulin via the...

Ubiquitin is linked to free calmodulin in the presence of the second messenger Ca2+ by the enzyme ubiquitin- calmodulin ligase (uCaM-synthetase; EC 6.3.2.21) without channeling the conjugates to degradation by the ATP- dependent 26S protease [1, 2]. Employing the natural substrates the enzymic components of the uCaM-synthetase hole, enzyme system c...

Ubiquityl-calmodulin synthetase (uCaM-synthetase) activity as detected in reticulocyte lysate and the crude extracts of rabbit tissues [FEBS Lett. 294 (1991) 229-233] has been well characterized as being essentially Ca(2+)-dependent (-Ca2+/+Ca2+ activity ratio: 0.15-0.2). However, during the purification of this enzyme on ubiquitin-Sepharose the Ca...

Recently we were able to show that calmodulin from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca(2+)-dependent manner by ubiquityl-calmodulin synthetase (uCaM-synthetase) from mammalian sources [R. Ziegenhagen and H.P. Jennissen (1990) FEBS Lett. 273, 253-256]. It was therefore of hig...

Previously we were able to show that purified calmodulins from vertebrates, plants (spinach) and the mold Neurospora crassa can be covalently conjugated to ubiquitin in a Ca(2+)-dependent manner. It was therefore pertinent to answer the question if a tissue extract contains all the components necessary for the endogenous synthesis of ubiquityl calm...

Enzyme activity capable of covalently linking ubiquitin to bovine calmodulin in an ATP-dependent manner has been detected in rabbit cardiac muscle demonstrating that this enzyme occurs not only in reticulocytes but also in other tissues and possibly all tissues and cells which contain calmodulin as intracellular Ca2+-acceptor protein. This is of sp...

3D-Rapid Prototyping (3D-RP) is a novel technique for the construction of highly accurate three-dimensional polyamide models of biomols. This method has been shown to be a valuable tool in the modeling of protein-protein-interactions as well as in the anal. of surface topog. Using this technique we were recently able to identify a so far unknown st...

3D-Rapid Prototyping (3D-RP) is a novel technique for the con- struction ofhighlyaccurate three-dimensional polyamide models of biomolecules. This method has been shown to be a valuable tool in the modeling of protein-protein-interactions as well as in the ana- lysis of surface topography. Using this technique we were recently able to identify a so...