Stefan Loher

IN VIVO AND IN VITRO EVALUATION OF FLEXIBLE, COTTONWOOL-LIKE NANOCOMPOSITES AS BONE SUBSTITUTE MATERIAL FOR COMPLEX DEFECTS

The easy clinical handling and applicability of biomaterials has become a focus of materials research due to rapidly increasing time and cost pressures in the public health sector. The present study assesses the in vitro and in vivo performance of a flexible, mouldable, cottonwool-like nanocomposite based on poly(lactide-co-glycolide) and amorphous tricalcium phosphate nanoparticles (PLGA/TCP 60:40). Immersion in simulated body fluid showed exceptional in vitro bioactivity for TCP-containing fibres (mass gain: 18%, 2 days, HAp deposition). Bone regeneration was quantitatively investigated by creating four circular non-critical-size calvarial defects in New Zealand White rabbits. The defects were filled with the easy applicable cottonwool-like PLGA/TCP fibres or PLGA alone. Porous bovine-derived mineral (Bio-Oss) was used as a positive control and cavities left empty served as a negative control. The area fraction of newly formed bone (4 weeks implantation) was significantly increased for TCP-containing fibres compared to pure PLGA (histological and micro-computed tomographic analysis). A spongiosa-like structure of the newly formed bone tissue was observed for PLGA/TCP nanocomposites, whereas Bio-Oss-treated defects afforded a solid cortical bone.

Micro-organism-Triggered Release of Silver Nanoparticles from Biodegradable Oxide Carriers Allows Preparation of Self-Sterilizing Polymer Surfaces

The antimicrobial activity of silver has attracted significant research interest and contributes to an exponentially growing use of this noble metal in commodity products. In this investigation, we describe a general approach to increase the antimicrobial activity of a silver-containing surface by two to three orders of magnitude. The use of 1-2-nm silver particles decorating the surface of 20-50-nm carrier particles consisting of a phosphate-based, biodegradable ceramic allows the triggered release of silver in the presence of a growing microorganism. This effect is based on the organisms requirements for mineral uptake during growth creating a flux of calcium, phosphate, and other ions to the organism. The growing micro-organism dissolves the carrier containing these nutrients and thereby releases the silver nanoparticles. Further, we demonstrate the rapid self-sterilization of polymer surfaces containing silver on calcium phosphate nanoparticles using a series of human pathogens. Colony-forming units (viable bacteria or fungi counts) have been routinely reduced below detection limit and suggest application of these self-sterilizing surfaces in hospital environments, food and pharmaceutical processing, and personal care.

Improved degradation and bioactivity of amorphous aerosol derived tricalcium phosphate nanoparticles in poly(lactide-co-glycolide)

The industrially used flame synthesis of silica polymer fillers was extended to amorphous tricalcium phosphate (a-TCP) nanoparticles and resulted in a similar morphology as the traditionally used polymer fillers. Doping of poly(lactide-co-glycolide) (PLGA) with such highly agglomerated a-TCP was investigated for mechanical properties, increased in vitro biodegradation and the formation of a hydroxyapatite layer on the surface of the nanocomposite. PLGA films with particle loadings ranging from 0 to 30 wt% were prepared by solvent casting. Degradation in simulated body fluid (SBF) at 37 °C under sterile conditions for up to 42 days was followed by Raman spectroscopy, scanning electron microscopy (SEM), thermal analysis and tensile tests. The presence of nanoparticles in the PLGA matrix slightly increased the Youngs modulus up to 30% compared to pure polymer reference materials. The nanoparticle doped films showed a significantly increased loss of polymer mass during degradation. Scanning electron microscopy images of doped films showed that the SBF degraded the PLGA by corrosion as facilitated by the incorporation of nanoparticulate calcium phosphate. Raman spectroscopy revealed that the deposition of about 10 nm sized hydroxyapatite crystallites on the surface of doped PLGA films was strongly increased by the addition of tricalcium phosphate fillers. The combination of increased hydroxyapatite formation and enhanced polymer degradation may suggest the use of such amorphous, aerosol derived a-TCP fillers for applications in non-load-bearing implant sites.

Flexible, silver containing nanocomposites for the repair of bone defects: antimicrobial effect against E. coli infection and comparison to tetracycline containing scaffolds

Bone regeneration in infected tissue or areas with high bacteria concentrations such as the oral cavity requires combining disinfection with biomaterial properties. Classical antibiotics typically provide excellent short term protection against re-infection of a defect but are typically washed out of an operation site within days. The present work investigates the use of silver on amorphous tricalcium phosphate (TCP) nanoparticles for electrospun, highly porous poly(lactide-co-glyclolide) (PLGA) fibrous composites. In vitro bioactivity tests of the wool-like composite PLGA/Ag-TCP (80 : 20) containing 0.5 wt% silver showed rapid hydroxyapatite deposition on the nanocomposite within 2 days. Antibacterial tests using E. coli demonstrated a strongly prolonged antibacterial effect of the scaffolds containing finely dispersed silver on TCP if compared to current clinically used methods based on soaking the scaffolds with a tetracycline solution prior to implantation.

Flame synthesis of calcium carbonate nanoparticles

Calcium carbonate nanoparticles of 20-50 nm size were obtained from a flame spray process where combustion of specific calcium-containing precursors results in amorphous or crystalline calcium carbonate particles depending on the spray flow conditions.