Band 4, Heft 1

No abstract available

No abstract available

No abstract available

Surface roughness is a vital factor for medical implants since the cells of the surrounding tissue interact with the underlying substrate on the micro- and nanometer scales. In order to improve the surface morphology of implants, appropriate large-area micro- and nanostructuring techniques have to be identified being applicable to irregularly shaped structures. We demonstrate that plasma treatments of polyetheretherketone (PEEK) thin films produce nanostructured surfaces in a reproducible manner. They are easily tailored by varying plasma intensity using oxygen and ammonia as process gases. It was observed that roughness and nanostructure density linearly depend on plasma intensity. Oxygen plasma turned out to exhibit a stronger effect compared to ammonia plasma at the same processing conditions. For cell interaction studies, the mean size of the nanostructures was intentionally varied between 10 nm and 100 nm. In vitro experiments revealed that human mesenchymal stem cells (hMSC) adhere inhomogenously on untreated PEEK films, but the plasma treatment with oxygen or ammonia allows the hMSC to adhere and proliferate. Fluorescence microscopy of the cells on the PEEK films turned out to be difficult because of the strong auto-fluorescence of the PEEK substrate. Stains including the whole cell vital stain Calcein-AM allowed cell morphology studies on plasma-treated PEEK films. In the case of the analysis of cell compartments such as the actin cytoskeleton, confocal laser scanning microscopy (CLSM) was successfully applied.

The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand. A gene activated matrix is a biomaterial with embedded gene vectors that will genetically modify cells embedded in or colonising the matrix. The platform comprises modules that self-adapt to the biological environment and that can be independently addressed with endogenous biological and exogenous physical or pharmacological stimuli, resulting in a temporally and spatially coordinated growth factor gene expression pattern. This reproduces, within the matrix, key elements of natural tissue formation. The modules are a biomimetic hyaluronan gel, a ceramic matrix, growth factor-encoding gene vector nanoparticles, magnetic nanoparticles and mesenchymal stem cells. Anatomical adaptivity is achieved with engineered thermal properties of the polymer matrix, which embeds other modules, selected according to functional requirements. Mechanical support is provided by Micro Macroporous Biphasic Calcium Phosphate (MBCP™), a resorbable material approved for clinical use. Spatiotemporal control of bioactivity and responsiveness to physiological conditions is represented, firstly, in the spatial distribution and release profiles of gene vectors within the composite matrix and, secondly, by letting local and external biological or physical stimuli activate the promoters driving the expression of vector-encoded growth factor transgenes. This concept is implemented by a multidisciplinary team from leading European institutions. Here, we report on the concepts, objectives and some preliminary results of the GAMBA project which is funded in 7th Framework Programme of the European Union THEME [NMP-2009-2.3-1], Biomimetic gels and polymers for tissue repair.

Infusion, or hypersensitivity reactions (HSRs) are frequent side effects of i.v. administered nanomedicines and biologicals. These, mostly mild and well tolerated, but occasionally severe or fatal allergic reactions represent a hemo-incompatibility due to activation of the complement (C) system. This review details the HSRs caused by marketed nanomedicines (liposomal drugs, micellar systems, polymer-conjugates of proteins, imaging agents, drug carrier nanosystems) and antibody therapeutics (mAbs), pointing out the remarkable similarity of clinical symptoms and difference from true (IgE-mediated) allergy. Beside the essentials, such as terminology, prevalence, risk factors and molecular and cellular mechanism of C activation-related pseudoallergy (CARPA) caused by the above agents, the paper highlights the biological rationale of these reactions, i.e., misinterpretation of nanoparticulate drugs by the immune system as pathogenic viruses, and C activation being an inherent function of mAbs. The public, as well as regulatory agencies are increasingly aware of the safety risks of possibly severe adverse immune reaction of drugs in the above categories, expressing need for new and appropriate immune toxicity tests in the preclinical stage. Here we outline and comment on the available methods for C activation and CARPA testing in vitro and in vivo, namely, the ELISA of C cleavage products (C3a, C5a, C4d, Bb, SC5b-9), the hemolytic (CH50) C assay, FACS measurement of basophil leukocyte activation, a – potentially – multiplex bead assay for C activation byproducts, the porcine assay of nanoparticle-induced cardiopulmonary distress and other CARPA tests in animals. The proven parallelisms between C activation and HSRs in vivo provide rationale for using these tests as predictors of infusion hypersensitivity, and the review suggests a decision tree for their use.

No abstract available.