Chemical-physical characterization and in vitro preliminary biological assessment of hyaluronic acid benzyl ester-hydroxyapatite composite.

HYAFF11 is a biocompatible, biodegradable benzyl ester of hyaluronic acid. However, in order to use it for orthopedic application, its mechanical performance needs to be improved. In this study, a novel composite based on HYAFF11 polymer matrix reinforced with hydroxylapatite (HA) has been developed. Its advantage is having a similar component of the mineral phase of bone resulting in favorable osteoconductive properties. The present study has examined the compressive mechanical and surface chemical-physical properties of the novel HYAFF11-HA composite. Preliminary biological investigations, including pH and cytotoxicity studies of the material extracts, have also been performed using an in vitro primary human osteoblast-like cell model. Moreover, protein, especially fibronectin adsorption has been investigated following incubation in culture medium and human plasma. The results show a grainy surface topography composed mainly of C, P, and Ca, with a Ca/P atomic ratio indicating HA on the composite surface. Mechanical analysis shows an improvement of the compressive properties of HYAFF11 matrix, both in the dry and swollen states, with values in the range of that of spongy bone. No cytotoxic effects and no inhibition of cell proliferation have been observed in the presence of the material extracts with pH values within acceptable ranges for cell vitality. Protein studies reveal a similar pattern, but a higher amount of fibronectin following incubation in human plasma when compared with culture medium. The results show that the novel HYAFF11-HA composite shows a great potential for application in orthopedic fields, especially as vertebral trabecular bone substitute.

Injectable calcium-phosphate-based composites for skeletal bone treatments.

Alpha-tricalcium-phosphate-based bone cements hydrolyze and set, producing calcium-deficient hydroxyapatite. They can result in an effective solution for bone defect reconstruction due to their biocompatibility, bioactivity and adaptation to shape and bone defect sizes, together with an excellent contact between bone and graft. Moreover, the integration of hydrogel phase based on poly(vinyl alcohol) (PVA) to H-cem-composed of α-tricalcium phosphate (98% wt) and hydroxyapatite (2% wt)-allows improving the mechanical and biological properties of the cement. The aim of this work was to evaluate the influence of the PVA on relevant properties for the final use of the injectable bone substitute, such as setting, hardening, injectability and in vivo behaviour. It was shown that by using PVA it is possible to modulate the setting and hardening properties: large increase in injectability time (1 h) in relation with the plain cement (few minutes) was achieved. Moreover, in vivo tests confirmed the ability of the composite to enhance bone healing in trabecular tissue. Histological results from critical size defects produced in rabbit distal femoral condyles showed after 12 weeks implantation a greater deposition of new tissue on bone-composite interfaces in comparison to bone-cement interfaces. The quality of bone growth was confirmed through histomorphometric and microhardness analysis. Bone formation in the composite implantation sites was significantly higher than in H-cem implants at both times of evaluation.

Biodegradable and semi-biodegradable composite hydrogels as bone substitutes: morphology and mechanical characterization.

Biodegradable and semi-biodegradable composite hydrogels are proposed as bone substitutes. They consist of an hydrophilic biodegradable polymer (HYAFF 11) as matrix and two ceramic powders (alpha-TCP and HA) as reinforcement. Both components of these composites have been of great interest in biomedical applications due to their excellent biocompatibility and tissue interactions, however they have never been investigated as bone substitute composites. Morphological and mechanical analysis have shown that the two fillers behave in a very different way. In the HYAFF 11/alpha-TCP composite, alpha-TCP is able to hydrolyze in contact with water while in the HYAFF 11 matrix. As a result, the composite sets and hardens, and entangled CDHA crystals are formed in the hydrogel phase and increases in the mechanical properties are obtained. In the HYAFF11/HA composite the ceramic reinforcement acts as inert phase leading to lower mechanical properties. Both mechanical properties and microstructure analysis have demonstrated the possibility to design hydrophilic biodegradable composite structures for bone tissue substitution applications.