Apatite/Chitosan Composites Formed by Cold Sintering for Drug Delivery and Bone Tissue Engineering Applications.

In the biomedical field, nanocrystalline hydroxyapatite is still one of the most attractive candidates as a bone substitute material due to its analogies with native bone mineral features regarding chemical composition, bioactivity and osteoconductivity. Ion substitution and low crystallinity are also fundamental characteristics of bone apatite, making it metastable, bioresorbable and reactive. In the present work, biomimetic apatite and apatite/chitosan composites were produced by dissolution-precipitation synthesis, using mussel shells as a calcium biogenic source. With an eye on possible bone reconstruction and drug delivery applications, apatite/chitosan composites were loaded with strontium ranelate, an antiosteoporotic drug. Due to the metastability and temperature sensitivity of the produced composites, sintering could be carried out by conventional methods, and therefore, cold sintering was selected for the densification of the materials. The composites were consolidated up to ~90% relative density by applying a uniaxial pressure up to 1.5 GPa at room temperature for 10 min. Both the synthesised powders and cold-sintered samples were characterised from a physical and chemical point of view to demonstrate the effective production of biomimetic apatite/chitosan composites from mussel shells and exclude possible structural changes after sintering. Preliminary in vitro tests were also performed, which revealed a sustained release of strontium ranelate for about 19 days and no cytotoxicity towards human osteoblastic-like cells (MG63) exposed up to 72 h to the drug-containing composite extract.

Speedy bioceramics: Rapid densification of tricalcium phosphate by ultrafast high-temperature sintering.

Due to unique osteogenic properties, tricalcium phosphate (TCP) has gained relevance in the field of bone repair. The development of novel and rapid sintering routes is of particular interest since TCP undergoes to high-temperature phase transitions and is widely employed in osteoconductive coatings on thermally-sensitive metal substrates. In the present work, TCP bioceramics was innovatively obtained by Ultrafast High-temperature Sintering (UHS). Ca-deficient hydroxyapatite nano-powder produced by mechanochemical synthesis of mussel shell-derived calcium carbonate was used to prepare the green samples by uniaxial pressing. These were introduced within a graphite felt which was rapidly heated by an electrical current flow, reaching heating rates exceeding 1200 °C min-1. Dense (> 93%) ceramics were manufactured in less than 3 min using currents between 25 and 30 A. Both ß and α-TCP were detected in the sintered components with proportions depending on the applied current. Preliminary tests confirmed that the artifacts do not possess cytotoxic effects and possess mechanical properties similar to conventionally sintered materials. The overall results prove the applicability of UHS to bioceramics paving the way to new rapid processing routes for biomedical components.

Nano-Hydroxyapatite Derived from Biogenic and Bioinspired Calcium Carbonates: Synthesis and In Vitro Bioactivity.

Biogenic calcium carbonates naturally contain ions that can be beneficial for bone regeneration and therefore are attractive resources for the production of bioactive calcium phosphates. In the present work, cuttlefish bones, mussel shells, chicken eggshells and bioinspired amorphous calcium carbonate were used to synthesize hydroxyapatite nano-powders which were consolidated into cylindrical pellets by uniaxial pressing and sintering 800-1100 °C. Mineralogical, structural and chemical composition were studied by SEM, XRD, inductively coupled plasma/optical emission spectroscopy (ICP/OES). The results show that the phase composition of the sintered materials depends on the Ca/P molar ratio and on the specific CaCO3 source, very likely associated with the presence of some doping elements like Mg2+ in eggshell and Sr2+ in cuttlebone. Different CaCO3 sources also resulted in variable densification and sintering temperature. Preliminary in vitro tests were carried out (by the LDH assay) and they did not reveal any cytotoxic effects, while good cell adhesion and proliferation was observed at day 1, 3 and 5 after seeding through confocal microscopy. Among the different tested materials, those derived from eggshells and sintered at 900 °C promoted the best cell adhesion pattern, while those from cuttlebone and amorphous calcium carbonate showed round-shaped cells and poorer cell-to-cell interconnection.