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A wide variety of titanium implant modifications have been developed to improve tissue- or cell-material interactions including bone bonding, implant failure, and contact osteogenesis. Osteogenesis can be stimulated by mechanobiological signals such as topography though translation of in vivo reactions to in vitro bioactivity and stem cell culture data, and vice versa, is challenging. We hypothesized that a systematic in vitro approach comparing clinically well-accepted implant surface topographical modifications could shed light on potential cell biological mechanisms provoked by submicron-, micron- or macrostructured surfaces. In this study, we investigated the response of umbilical cord derived mesenchymal stromal cells (UC-MSCs) to anodized, particle blasted, and plasma sprayed highly porous Plasmapore surfaces, which is known to promote bony ingrowth in vivo. After 21 days, UC-MSCs undergo a morphological shift from a 2D to 3D behavior on micro- or macrostructures visualized by actin-vinculin fluorescence and are able to fill the porous surfaces completely. Cell viability after 7 days was significantly decreased on the micro- and macrostructured surfaces particle blasted and Plasmapore, compared to polished controls. The analysis of osteogenic differentiation under noninduced conditions revealed a significantly elevated ALP activity on Plasmapore, indicating a beneficial effect of this macrostructured surface toward osteogenic differentiation supported by late elevated gene expression of osteopontin evaluated by qPCR. Mineralization as well as in vitro bioactivity was pronounced on anodized surfaces. Our findings point to synergistic implant modification strategies allowing early contact osteogenesis and bone ingrowth for future implant designs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 180-191, 2018. [ABSTRACT FROM AUTHOR]

In this study, the production of poly(ethylene glycol) diacrylate (PEGDA) scaffolds by micro-stereolithography based on diode laser curing (DLC) is demonstrated. Sample scaffolds are also loaded with acetylsalicylic acid (ASS) as model drug. The samples are immersed in physiological NaCl solution and the drug release characteristics are tested. We show that DLC is a useful technique to prepare drug-loaded PEGDA scaffolds. The compressive strength of the enriched and DLC-cured PEGDA is between 7 and 10 MPa, dependent on ASS concentration. ASS free samples reach 14 MPa. The release experiments show an initial burst release phase and the ASS is released within the first 3 hours. [ABSTRACT FROM AUTHOR]

The improvement of well-established local drug delivery (LDD) systems, often providing drug release independently of their need, is a challenge of current implant technology. Systems that sense signals caused by a certain disease, judge the magnitude of the signal and act to release the right amount of drug in response are hence searched for. Specific responsive hydrogels with antibody-antigen cross-links, whose non-covalent interaction is broken in the presence of the corresponding antigen and reclosed in its absence, are a promising candidate. However, the challenging implementation of such antigen-responsive hydrogels as implant coating and their applicability for implant-associated LDD systems have not been explored so far. In this context and in order to define adequate gel properties for the envisaged application, we prepared a matrix at examples of polyacrylamide hydrogels of different gel architectures, gel contents and cross-linking degrees and investigated their impact on the permeation of the differently sized model proteins bovine serum albumin (BSA), protein A and myoglobin in a specifically designed chamber simulating an implant-associated LDD system and the mechanical stability of the polymeric network. Water uptake, as estimated by Karl Fischer titration, which was mainly influenced by gel content, seems to primarily govern drug permeability and mechanical stability. Within the investigated matrix, a medium gel content of 15.0 w% acrylamide and N,N′-methylenebisacrylamide evidenced low drug permeability, enough tensile strength and flexibility for integration of antibody-antigen cross-links, which we could successfully evidence via fluorescence microscopy. A stimulus-triggered release of BSA through such a hydrogel could be moreover demonstrated. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An easy and efficient route to synthesize gel materials based on polymeric ionic liquids (PILs) is presented. The radical polymerization of imidazolium (Im)-based ionic liquids (ILs) bearing a vinyl group ([VEIm][Br], [VEIm][Ac], [VBIm][Br], [VBIm][Cl]) with crosslinker (CL) N,N′-methylenebisacrylamide (Bis) in water results in polyionic liquid hydrogels. Thermal and mechanical properties (tensile and compression tests) are investigated and compared with two different types of hydrogels. One is a polyacrylamide (PAAm) hydrogel having covalent-type crosslinking. The other is an alginate-based hydrogel having ionic-type crosslinking. Prepared IL-hydrogel materials provide favorable flexibility, adjustable by varying the CL ratio and water content. The higher the CL ratio is, the higher the fragility of the gel matrix. The gelation time of the hydrogels depends on the alkyl chain length, as well as the size of the anion. [ABSTRACT FROM AUTHOR]

Aiming at a speed up of the re-endothelialization process of biodegradable endovascular implants, novel approaches for the functionalization of poly( l-lactide) (PLLA) with anti-CD34 antibodies were established. We propose a three-step process involving PLLA surface activation with functional amino groups, attachment of a protein repelling peptide spacer, and covalent random or site-selective immobilization of the antibodies. Obtainable antibody surface densities and antigen binding capacities were thoroughly evaluated by means of enzyme-linked immunosorbent assay. Results indicate that a lower amount of anchoring sites on the antibody favors high coupling efficiency, while localization of the anchoring sites, facing the antigen binding moiety, strongly enhances the antigen capture capacity of the support. Besides minimization of physisorption and cell adhesion exemplarily shown with bovine serum albumin, avidin, and human umbilical vein endothelial cells, respectively, the inclusion of the protein-repelling spacer strengthened this effect, yielding antigen capture capacities exceeding values so far reported in literature. In contrast, the number of amino groups on the PLLA surfaces, which is indeed highly dependent on the applied activation procedure, does not seem to influence antibody coupling efficiency and antigen capture capacity considerably. This allows the choice of surface activation treatment, plasma or wet-chemical, regarding other processing parameters as for instance sterilizability or favored modification depth. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 345-355, 2014. [ABSTRACT FROM AUTHOR]

Magnesium-based bioabsorbable cardiovascular stents have been developed to overcome limitations of permanent metallic stents, such as late stent thrombosis. During stent degradation, endothelial and smooth muscle cells will be exposed to locally high magnesium concentrations with yet unknown physiological consequences. Here, we investigated the effects of elevated magnesium concentrations on human coronary artery endothelial and smooth muscle cell (HCAEC, HCASMC) growth and gene expression. In the course of 24 h after incubation with magnesium chloride solutions (1 or 10 m M) intracellular magnesium level in HCASMC raised from 0.55 ± 0.25 m M (1 m M) to 1.38 ± 0.95 m M (10 m M), while no increase was detected in HCAEC. Accordingly, a DNA microarray-based study identified 69 magnesium regulated transcripts in HCAEC, but 2172 magnesium regulated transcripts in HCASMC. Notably, a significant regulation of various growth factors and extracellular matrix components was observed. In contrast, viability and proliferation of HCAEC were increased at concentrations of up to 25 m M magnesium chloride, while in HCASMC viability and proliferation appeared to be unaffected. Taken together, our data indicate that magnesium halts smooth muscle cell proliferation and stimulates endothelial cell proliferation, which might translate into a beneficial effect in the setting of stent associated vascular injury. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. [ABSTRACT FROM AUTHOR]

Within this study, chemically modified polymer surfaces were to be developed, which should enhance the subsequent immobilization of various bioactive substances. To improve the hemocompatibility and endothelialization of poly(ε-caprolactone) (PCL) intended as scaffold material for bioartificial vessel prostheses, terminal amino groups via ammonia (NH3) plasma, oxygen (O2) plasma/aminopropyltriethoxysilane (APTES), and 4,4′-methylenebis(phenyl isocyanate) (MDI)/water were provided. Then, immobilization of the anti-inflammatory and antithrombogenic model drug acetylsalicylic acid (ASA) and vascular endothelial growth factor (VEGF) were performed by employing N,N-disuccinimidyl carbonate (DSC) as crosslinker. Contact angle and fluorescence measurements, X-ray photoelectron spectroscopy and infrared spectroscopy confirmed the surface modification. Here the highest functionalization was observed for the O2 plasma/APTES modification. Furthermore, biocompatibility studies demonstrated that the surface reactions have no negative influence, neither on the viability of L929 mouse fibroblasts, nor on primary or secondary hemostasis. Release studies showed that the immobilization of ASA and VEGF on the modified PCL surface via DSC is greatly improved compared to the adsorption-only reference. The advantage of DSC is that it immobilizes both bioactive substances via non-hydrolyzable and/or hydrolyzable covalent bonding. The highest ASA loading and cumulative release was detected using NH3 plasma-activated PCL samples. For VEGF, the O2 plasma/APTES-modified PCL samples were most efficient with regard to loading and cumulative release. In conclusion, both modifications are promising methods to optimize PCL as scaffold material for bioartificial vessel prostheses. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. [ABSTRACT FROM AUTHOR]

Implantation of a glaucoma drainage system is an appropriate therapeutic intervention in some glaucoma patients. However, one drawback with this approach is the fibrotic tissue response to the implant material, leading to reduced flow of aqueous liquid or complete blockage of the drainage system. As a basis for developing an aqueous shunt we report here investigations with poly(3-hydroxybutyrate) (P(3HB)) and poly(4-hydroxybutyrate) (P(4HB)) as polymer matrices and with paclitaxel (PTX) and triamcinolone acetonide (TA) as drugs that might, in combination, delay or prevent the process of fibrosis by reducing fibroblast activity. P(3HB) and P(4HB) were fabricated into test prototypes with 500 μm outer and 200 μm inner diameter and ∼1 cm length. The antiproliferative agent PTX and the anti-inflammatory agent TA were incorporated into the polymer matrices and were released by diffusion. In vitro cell assays demonstrated that the polymers have the potential to reduce fibroblast viability, while TA showed differential inhibition of Tenon fibroblasts, but not cornea keratocytes. Implantation of polymer disks and prototype devices into rabbit eyes confirmed the good biocompatibility of the materials. The combined use of a poly(hydroxybutyrate) polymer with PTX or TA has the potential to reduce the fibrosis associated with conventional glaucoma drainage systems. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. [ABSTRACT FROM AUTHOR]

In body regions where damage and bleeding must be avoided, a substitute for mechanical tissue fixation by sutures or staplers is needed. Since tissue adhesives provide easy and fast handling they are a promising alternative. The present study reports the development and analysis of a tissue adhesive that consists of two adhesive components: hexamethylene diisocyanate (HDI) functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO) and chitosan chloride. This composition was chosen based on preliminary studies on several chain elongation agents. The present study evaluates this adhesive system by IR-spectroscopy, tensile tests, and gel point measurements in comparison to fibrin glue. The system's in vitro biocompatibility was tested with mouse fibroblasts (L929) according to ISO 10993-5. Furthermore, an implantation study was performed in SPF-Wistar rats. The adhesive strength of manually applied mixtures or mixtures applied by double chamber syringes with a mixing extruder was determined to be significantly higher than that of fibrin glue on bovine muscle tissue at 37°C. Tensile strength increased further when exposure time of the adhesive was increased from 10 min to 48 h. The rheological gel point determination showed that the mixture of ELA-NCO/DMSO and chitosan chloride offers a time window large enough to readjust the fused joint during surgery, as opposed to fibrin glue. Additionally, the in vitro and in vivo biocompatibility studies of the adhesive system revealed no toxic effects on the surrounding tissue. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. [ABSTRACT FROM AUTHOR]

Tissue adhesives are a valuable alternative for mechanical tissue fixation by sutures or staples. Adhesives are desirable in body regions where damage and bleeding must be avoided. Tissue adhesives provide easy and fast handling. This study reports the development of a tissue adhesive based on 1,2‐ethylene glycol bis(dilactic acid) (ELA) functionalized with hexamethylene diisocyanate (HDI) to produce isocyanate terminated ELA‐NCO which was characterized by NMR and FTIR spectroscopy. ELA‐NCO together with chain elongation agents forms an adhesive system suitable for tissue fixation. Several biodegradable polymers, such as hyaluronic acid, gelatin, chitosan acetate, and chitosan chloride were tested as chain elongation agents to obtain an adhesive system and studied on bovine muscle tissue to evaluate their adhesive strength and compared to fibrin glue. Tensile strength of glued joints was determined by a Zwick universal testing machine at ambient temperature. Mixtures of ELA‐NCO and chitosan acetate or chloride, showed significantly higher adhesive strength than fibrin glue. Reaction between ELA‐NCO and chitosan chloride produced polyurethane was traced by FTIR spectroscopy. NMR, FTIR, and rheological measurements demonstrated that ELA‐NCO and chitosan chloride can be sterilized by γ‐rays or superheated water vapor without alterations, respectively. A mixture of ELA‐NCO and chitosan chloride can be useful as medical tissue adhesive. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. [ABSTRACT FROM AUTHOR]

To utilize the Icare tonometer TAO1 for intraocular pressure (IOP) determination in experimental animals. To calculate true IOP calibration functions for rabbit and porcine eyes. Enucleated eyes of 3-year-old healthy experimental rabbits (New Zealand white), and healthy 1 year old experimental pigs (Deutsche Landrasse) were used for the determination of IOP. Manometric (Geuder GmbH, Heidelberg/Germany) and rebound tonometry (Icare tonometer TAO1, Icare, Helsinki/Finland) were used to record IOP in enucleated animal eyes (rabbit n = 2, pig n = 3). The Icare tonometer TAO1 measurements underestimated true IOP by 37-60% in rabbit eyes and 17-63% in porcine eyes. IOP values obtained by both rebound and manometric tonometry for rabbit and porcine eyes followed a linear regression curve. Linear functions were calculated to correct the Icare tonometer TAO1 measurements to true IOP for both rabbit ( p = 1.4244 p + 4.2421) and porcine eyes ( p = 1.0799 p + 5.8557). The Icare tonometer TAO1 can be utilized for IOP determination in rabbit and porcine eyes when measured values are corrected with the appropriate linear function. [ABSTRACT FROM AUTHOR]