The effect of starch-based biomaterials on leukocyte adhesion and activation in vitro

Leukocyte adhesion to biomaterials has long been recognised as a key element to determine their inflammatory potential. Results regarding leukocyte adhesion and activation are contradictory in some aspects of the material’s effect in determining these events. It is clear that together with the wettability or hydrophilicity/hydrophobicity, the roughness of a substrate has a major effect on leukocyte adhesion. Both the chemical and physical properties of a material influence the adsorbed proteins layer which in turn determines the adhesion of cells. In this work polymorphonuclear (PMN) cells and a mixed population of monocytes/macrophages and lymphocytes (mononuclear cells) were cultured separately with a range of starch-based materials and composites with hydroxyapatite (HA). A combination of both reflected light microscopy and scanning electron microscopy (SEM) was used in order to study the leukocyte morphology. The quantification of the enzyme lactate dehydrogenase (LDH) was used to determine the number of viable cells adhered to the polymers. Cell adhesion and activation was characterised by immunocytochemistry based on the expression of several adhesion molecules, crucial in the progress of an inflammatory response. This work supports previous in vitro studies with PMN and monocytes/macrophages, which demonstrated that there are several properties of the materials that can influence and determine their biological response. From our study, monocytes/macrophages and lymphocytes adhere in similar amounts to more hydrophobic (SPCL) and to moderately hydrophilic (SEVA-C) surfaces and do not preferentially adhere to rougher substrates (SCA). Contrarily, more hydrophilic surfaces (SCA) induced higher PMN adhesion and lower activation. In addition, the hydroxyapatite reinforcement induces changes in cell behaviour for some materials but not for others. The observed response to starch-based biodegradable polymers was not significantly different from the control materials. Thus, the results reported herein indicate the low potential of the starch-based biodegradable polymers to induce inflammation especially the HA reinforced composite materials

Circulating anti-citrullinated protein antibodies containing secretory component are prognostic for arthritis onset in at-risk patients

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development

Attenuation of acute inlammatory responses by surface nanotopography

The interaction between biology and non-viable surfaces is crucial for many organisms and cells. For example, bacterial cells need to adhere to mineral surfaces in the soil, plants climb and adhere to walls and marine organisms produce adhesives to cling to underwater rocks etc. In the human body, tissue needs to firmly adhere to the mineral surface of bone, but also to foreign materials when for example a biomaterial is implanted. The knowledge of how biology interacts with surfaces is hence important and interesting in many aspects. Within seconds after implantation of a biomaterial, proteins from the immune complement and coagulation systems adsorbs to the surface with possible adverse consequences for the patient. To overcome this, chemical surface modifications are readily employed. However, recently the significance of surface nanotopography for the adsorption of proteins, and attachment of cells have been acknowledged. To facilitate research on the interactions between biology and nanostructured substrates novel experimental surfaces with defined nanotopography and surface chemistry were developed. The surfaces are fabricated by binding gold nanoparticles to a gold surface, using a non-lithographic method and standard laboratory equipment. The surface chemistry was evaluated using XPS and ToF-SIMS. On these surfaces, the effect of surface nanotopography on the activation of the immune complement and activation of blood platelets was studied using QCM-D, SEM and fluorescence microscopy. It was found that although nanostructured surfaces adsorbed greater amount of serum proteins, activation of the immune complement was attenuated by surface nanotopography. A suggested mechanism is that the curvature of the nanoparticles prevents interaction between complement proteins. It was also found that blood platelets were activated to a lower degree on nanostructured surfaces and were sensitive to changes in nanoparticle size and inter-particle distance. These nanostructures surfaces can hopefully facilitate research on protein/cell interactions on nanostructured surfaces