Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice.

Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice.

The RGD coupling strategy determines the inflammatory response of human primary macrophages in vitro and angiogenesis in vivo.

Surface modifications of implants are frequently done using bioactive peptides. However, immune cells such as macrophages might evoke a rejection of an implant due to an undesired activation by the materials. Here, the influence of different strategies for peptide immobilization onto (poly)-vinylidene fluoride (PVDF) on inflammation and angiogenesis is studied.

Ovine carotid artery-derived cells as an optimized supportive cell layer in 2-D capillary network assays.

Background: Endothelial cell co-culture assays are differentiation assays which simulate the formation of capillary-like tubules with the aid of a supportive cell layer. Different cell types have been employed as a supportive cell layer, including human pulmonary artery smooth muscle cells (PASMCs) and human mammary fibroblasts. However, these sources of human tissue-derived cells are limited, and more readily accessible human or animal tissue-derived cell sources would simplify the endothelial cell co-culture assay.

Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction.

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo.

Biofunctionalized microfiber-assisted formation of intrinsic three-dimensional capillary-like structures.

Objectives: A vascular supply network is essential in engineered tissues >100-200-μm thickness. To control vascular network formation in vitro, we hypothesize that capillarization can be achieved locally by using fibers to position and guide vessel-forming endothelial cells within a three-dimensional (3D) matrix.

Materials And Methods: Biofunctionalization of poly-(L-lactic acid) (PLLA) fibers was performed by amino-functionalization and covalent binding of RGD peptides.

Dexamethasone released from cochlear implant coatings combined with a protein repellent hydrogel layer inhibits fibroblast proliferation.

The insertion of cochlear implants into the inner ear often causes inflammation and fibrosis inside the scala tympani and thus growth of fibrous tissue on the implant surface. This deposition leads to the loss of function in both electrical and laser-based implants. The design of this study was to realize fibroblast growth inhibition by dexamethasone (Dex) released from the base material of the implant [polydimethylsiloxane (PDMS)].

The role of SNAP-tag in technical approaches.

Biosensors are used for a variety of applications in medicine and biology. A critical step during the development of such devices is the coordination of biological and technical requirements. The design of the device, as well as of the sample chamber and its functionalized surface is of great importance.

Surface-modified silicone foils for intraocular implantation.

Background: Implantation of silicone materials like iris diaphragms into the eye can be complicated by cell migration and attachment. We studied polydimethylsiloxane (PDMS) foils coated with isocyanate terminated, star-shaped poly(ethylene glycol-stat-propylene glycol) (NCO-sP(EO-stat-PO)) equipped with heparin towards the inhibition of cell attachment without influencing cell viability.

Methods: Mouse fibroblasts L929 were cultured and seeded onto sterilized pieces of either uncoated NCO-sP(EO-stat-PO) or heparin-NCO-sP(EO-stat-PO) loaded foils.

Neutrophil-derived cathelicidin protects from neointimal hyperplasia.

Percutaneous transluminal angioplasty with stent implantation is used to dilate arteries narrowed by atherosclerotic plaques and to revascularize coronary arteries occluded by atherothrombosis in myocardial infarction. Commonly applied drug-eluting stents release antiproliferative or anti-inflammatory agents to reduce the incidence of in-stent stenosis. However, these stents may still lead to in-stent stenosis; they also show increased rates of late stent thrombosis, an obstacle to optimal revascularization possibly related to endothelial recovery.

Directed covalent immobilization of fluorescently labeled cytokines.

Cytokines are important mediators coordinating inflammation and wound healing in response to tissue damage and infection. Therefore, immobilization of cytokines on the surface of biomaterials is a promising approach to improve biocompatibility. Soluble cytokines signal through receptors on the cell surface leading to cell differentiation, proliferation, or other effector functions.

Controlling pH in shake flasks using polymer-based controlled-release discs with pre-determined release kinetics.

Background: There are significant differences in the culture conditions between small-scale screenings and large-scale fermentation processes. Production processes are usually conducted in fed-batch cultivation mode with active pH-monitoring and control. In contrast, screening experiments in shake flasks are usually conducted in batch mode without active pH-control, but with high buffer concentrations to prevent excessive pH-drifts.

Functionalization of electrospun poly(ε-caprolactone) fibers with the extracellular matrix-derived peptide GRGDS improves guidance of schwann cell migration and axonal growth.

The best available treatment of peripheral nerve lesions involves transplantation of an autologous nerve. This approach, however, entails sensory deficits at the donor site and requires additional surgery. Such limitations have motivated the search for a bioengineering solution to design artificial implants.

Electrospun, biofunctionalized fibers as tailored in vitro substrates for keratinocyte cell culture.

Cell adhesion preventing fiber surfaces were tailored differently with bioactive peptides (a fibronectin fragment (GRGDS), a collagen IV fragment (GEFYFDLRLKGDK) and a combination of both) to provide an artificial extracellular matrix as a substrate for HaCaT keratinocyte cell culture. Therefore, a polymer blend containing a six-arm star-shaped statistical copolymer of ethylene oxide and propylene oxide in the ratio 80:20 (NCO-sP[EO-co-PO]) and poly-[D,L-(lactide-co-glycolide)] (PLGA) was electrospun. The resulting fibers were biofunctionalized and investigated as in vitro substrates using the HaCaT kerationcyte cell line.

Bioresorbable electrospun fibers for immobilization of thiol-containing compounds.

For the reconstruction of functional tissue, biodegradable scaffolds providing specific surface functionality and a three-dimensional structure matching that of the damaged tissue are needed. Fibers capable of controlling cell-fiber interaction were produced by electrospinning of PDLLA-block-PEG with thiol-reactive end groups from a solvent mixture. The hydrophilic fibers uniquely combine minimized non-specific protein adsorption and well-defined surface reactivity allowing controlled immobilization of peptides and proteins.

Functionalization of electrospun fibers of poly(epsilon-caprolactone) with star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) for neuronal cell guidance.

Microfibers produced with electrospinning have recently been used in tissue engineering. In the development of artificial implants for nerve regeneration they are of particular interest as guidance structures for cell migration and axonal growth. Using electrospinning we produced parallel-orientated biocompatible fibers in the submicron range consisting of poly(epsilon-caprolactone) (PCL) and star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) (sPEG).

Solvent-free functionalization of silicone rubber and efficacy of PAAm brushes grafted from an amino-PPX layer against bacterial adhesion.

Silicone rubber is a frequently employed biomaterial that is prone to bacterial adhesion and biofilm formation. In this study, the surface of silicone rubber was solvent-free functionalized by chemical vapor deposition (CVD) of poly(o-amino-p-xylylene-co-p-xylylene (amino-PPX). Subsequently, the amino groups of the amino-PPX layer were used to introduce the initiator from a vapor phase for atom transfer radical polymerization of acrylamide to form polyacrylamide (PAAm) brushes.

Influence of particle size and material properties on mucociliary clearance from the airways.

Mucociliary clearance (MC), designed by evolution to eliminate inhaled and possibly noxious material from the airways, considerably limits the benefit of inhalation therapy. Although the principles of MC seem to be understood, there are still many open questions on mucociliary particle clearance. In this study a trachea-based in vitro model was used to investigate the effect of particle size, zeta-potential, and mucoadhesive particle properties on mucociliary particle clearance.

Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model.

Matrigel promotes angiogenesis in the myocardium from ischemic injury and prevents remodelling of the left ventricle. We assessed the therapeutic efficacy of intracardiac matrigel injection and matrigel-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, matrigel (250 μl) or phosphate-buffered solution (PBS) was delivered by intracardiac injection.

High-throughput screening of Hansenula polymorpha clones in the batch compared with the controlled-release fed-batch mode on a small scale.

Most large-scale production processes in biotechnology are performed in fed-batch operational mode. In contrast, the screenings for microbial production strains are run in batch mode, which results in the microorganisms being subjected to different physiological conditions. This significantly affects strain selection.

Bio-functionalized star PEG-coated PVDF surfaces for cytocompatibility-improved implant components.

Unmodified and GRGDS peptide-modified six arm PEG star based hydrogels (Star PEG) have been applied as a multifunctional, easy to handle coating system for textile polyvinylidene fluoride (PVDF) structures, which prevent unspecific protein and cell adsorption and control-specific cell adhesion. The reactive isocyanate-terminated Star PEG has been successfully applied to ammonia-plasma treated two- and three-dimensional PVDF surfaces. Easy modification of the surface hydrogel by mixing in of GRGDS peptide during the coating step or subsequent coupling of GRGDS was determined by TOF-SIMS.

Equalizing growth in high-throughput small scale cultivations via precultures operated in fed-batch mode.

An often underestimated problem when working with different clones in microtiter plates and shake flask screenings is the non-parallel and non-equal growth of batch cultures. These growth differences are caused by variances of individual clones regarding initial biomass concentration, lag-phase or specific growth rate. Problems arising from unequal growth kinetics are different induction points in expression studies or uneven cultivation periods at the time of harvest.

Disulfide-crosslinked electrospun poly(gamma-glutamic acid) nonwovens as reduction-responsive scaffolds.

Novel water-insoluble, and reduction-responsive nonwoven scaffolds were fabricated from gamma-PGA and tested in cell culture. An electrospinning method was developed to produce scaffolds of fibers with diameters of 0.05-0.

Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment.

A range of industrial H. polymorpha-based processes exist, most of them for the production of pharmaceuticals. The established industrial processes lean on the use of promoters derived from MOX and FMD, genes of the methanol metabolism pathway.

Human neural cell interactions with orientated electrospun nanofibers in vitro.

Aim: Electrospun nanofibers represent potent guidance substrates for nervous tissue repair. Development of nanofiber-based scaffolds for CNS repair requires, as a first step, an understanding of appropriate neural cell type-substrate interactions.

Materials & Methods: Astrocyte-nanofiber interactions (e.

Deposition of electrospun fibers on reactive substrates for in vitro investigations.

Recent in vitro studies with electrospun nanofibers have used a range of techniques. The in vitro system presented in this article describes electrospun fibers deposited onto chemically reactive substrates to provide fiber adherence and surface chemistry control of the substrate. Fibers of poly(epsilon-caprolactone) (PCL) or of a blend of PCL and collagen type I (C/PCL) were electrospun directly onto collectors coated with isocyanate-terminated star (polyethylene glycol) (sPEG).