Composites Based on Hydroxyapatite and Whey Protein Isolate for Applications in Bone Regeneration

The “Multifunctional biologically active composites for applications in bone regenerative medicine” project is carried out within the TEAM-NET program of the Foundation for Polish Science financed by the European Union under the European Regional Development Fund. The authors gratefully acknowledge the financial support. T.E.L.D. thanks N8 Agrifood for its financial support in the framework of the pump priming grant “Food2Bone”.Hydroxyapatite (HAp) is a bioactive ceramic with great potential for the regeneration of the skeletal system. However, its mechanical properties, especially its brittleness, limit its application. Therefore, in order to increase its ability to transmit stresses, it can be combined with a polymer phase, which increases its strength without eliminating the important aspect of bioactivity. The presented work focuses on obtaining organic–inorganic hydrogel materials based on whey protein isolate (WPI) reinforced with nano-HAp powder. The proportion of the ceramic phase was in the range of 0–15%. Firstly, a physicochemical analysis of the materials was performed using XRD, FT-IR and SEM. The hydrogel composites were subjected to swelling capacity measurements, potentiometric and conductivity analysis, and in vitro tests in four liquids: distilled water, Ringer’s fluid, artificial saliva, and simulated body fluid (SBF). The incubation results demonstrated the successful formation of new layers of apatite as a result of the interaction with the fluids. Additionally, the influence of the materials on the metabolic activity according to ISO 10993-5:2009 was evaluated by identifying direct contact cytotoxicity towards L-929 mouse fibroblasts, which served as a reference. Moreover, the stimulation of monocytes by hydrogels via the induction of nuclear factor (NF)-κB was investigated. The WPI/HAp composite hydrogels presented in this study therefore show great potential for use as novel bone substitutes

Infectious Agents as Stimuli of Trained Innate Immunity

The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells) after their stimulation with various infectious or non-infectious agents. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin) as well as viruses or even parasites are considered potent inducers of innate immune memory. Epigenetic cell reprogramming occurring at the heart of the phenomenon may provide a useful basis for designing novel prophylactic and therapeutic strategies to prevent and protect against multiple diseases. In this article, we present the current state of art on trained innate immunity occurring as a result of infectious agent induction. Additionally, we discuss the mechanisms of cell reprogramming and the implications for immune response stimulation/manipulation

Effects of Sterilization and Hydrolytic Degradation on the Structure, Morphology and Compressive Strength of Polylactide-Hydroxyapatite Composites

Composites based on polylactide (PLA) and hydroxyapatite (HA) were prepared using a thermally induced phase separation method. In the experimental design, the PLA with low weight-average molar mass (Mw) and high Mw were tested with the inclusion of HA synthesized as whiskers or hexagonal rods. In addition, the structure of HA whiskers was doped with Zn, whereas hexagonal rods were mixed with Sr salt. The composites were sterilized and then incubated in phosphate-buffered saline for 12 weeks at 37 °C, followed by characterization of pore size distribution, molecular properties, density and mechanical strength. Results showed a substantial reduction of PLA Mw for both polymers due to the preparation of composites, their sterilization and incubation. The distribution of pore size effectively increased after the degradation process, whereas the sterilization, furthermore, had an impact on pore size distribution depending on HA added. The inclusion of HA reduced to some extent the degradation of PLA quantitatively in the weight loss in vitro compared to the control without HA. All produced materials showed no cytotoxicity when validated against L929 mouse skin fibroblasts and hFOB 1.19 human osteoblasts. The lack of cytotoxicity was accompanied by the immunocompatibility with human monocytic cells that were able to detect pyrogenic contaminants