In vivo evaluation of bioactivity of alginate/chitosan based osteoplastic nanocomposites loaded with inorganic nanoparticles.

The influence of two nanostructured osteoplastic materials with different compositions: i) alginate (Alg) matrix, loaded with Zn2+ ions and nanostructured hydroxyapatite (HA) - S1/HA-Zn, and ii) chitosan (CS) matrix loaded with brushite nanoparticles (NPs, dicalcium phosphate dihydrate, DCPD) - S2/DCPD on the healing of an experimental femoral diaphysis defect was investigated. The structure of cellular elements and the lacunar tubular system of the regenerated bone tissue were studied by electron microscopy. Osteogenic cells on the surface and inside S1/HA-Zn formed bone tissue. On the 30th day, the latter had a reticulofibrous and later lamellar structure. On the 30th day, the S2/DCPD biomaterial was integrated mainly into connective tissue and, starting from the 90th day, into the bone tissue, which was formed only on its outer surface. Thus, it has been proven that both biomaterials contribute to the healing of bone wounds. The regenerative potential of the new bone tissue formation of S1/HA-Zn prevails over that of S2/DCPD.

In Vivo feature of the regenerative potential of chitosan and alginate based osteoplastic composites doped with calcium phosphates, zinc ions, and vitamin D2.

PURPOSE: In vivo comparison of the regenerative potential of two calcium phosphate-biopolymer osteoplastic composites: а) based on alginate (Alg) and hydroxyapatite (HA) - Alg/HA/CS/Zn/D2, b) based on chitosan (CS) and brushite (DCPD) - CS/DCPD/D2. MATERIALS AND METHODS: 36 white male laboratory rats aged six months were used. A defect to the bone marrow canal in the middle of the femur diaphysis was made with a dental bur of 2 mm. The bone defect healed under the blood clot (control) in the different animal groups and was filled with Alg/HA/CS/Zn/D2 and CS/DCPD/D2. The regeneration of the bone defect was studied on the 30th, 90th, and 140th days by computer tomography (CT). RESULTS: On the 30th day, all groups' implantation site optical density (OD) was significantly lower than that of the adjacent maternal bone (MB). Intensity of bone formation for Alg/HA/CS/Zn/D2 exceeds CS/DCPD/D2. On the 90th day, the bone trauma site OD with Alg/HA/CS/Zn/D2 (1725.4 ± 86 HU) and CS/DCPD/D2 (1484.9 ± 69 HU) exceeded the OD of the control (942.5 ± 55 HU). On the 140th day, the OD of Alg/HA/CS/Zn/D2 and CS/DCPD/D2 implantation sites was higher than Control and MB OD. Visually, the area of the past injury with the Alg/HA/CS/Zn/D2 could be detected only by the presence of an endosteal bone callus and in the case of CS/DCPD/D2 - by the shadow of the remaining biomaterial in the bone marrow canal. CONCLUSIONS: According to CT data, Alg/HA/CS/Zn/D2 and CS/DCPD/D2 contribute to the complete healing of the femoral diaphysis defect in 140 days, but the regenerative potential of Alg/HA/CS/Zn/D2 from 30 days to 140 days is higher than CS/DCPD/D2 biomaterial.

Effect of zinc oxide micro- and nanoparticles on cytotoxicity, antimicrobial activity and mechanical properties of apatite-polymer osteoplastic material.

This work is devoted to the comparison of the physical and biological properties of synthesized osteoplastic composites with an experimentally determined content (375 µg/g) of the micro (ZnOMPs) and nano (ZnONPs) particles, immobilized in Hydroxyapatite-Alginate-Chitosan matrix (HA-Alg-CS). ZnONPs show pronounced antimicrobial activity against E.coli ATCC 25922 and S. aureus ATCC 25923, while ZnOMPs only in the CS presence. Composites containing ZnONPs/MPs do not have a toxic effect on bone-forming cells - osteoblasts, preserving their ability to biomineralization. ZnOMPs and ZnONPs to varying degrees, but significantly affect composites' swelling, porosity, shape stability, and prolong vitamin D3 release for 120h, compared to Control. Composites do not demonstrate unwanted "burst release." ZnONPs/MPs increase Youngs' modulus of the HA-Alg matrix, namely 348 â†’ 419 MPa (ZnOMPs), 348 â†’ 646 MPa (ZnONPs), and weaken the plastic (irreversible) deformations. The compressive strength of HA-Alg and HA-Alg/CS matrixes containing ZnONPs (178 MPa and 251 MPa, respectively) is in the range of values for native cortical bone (170-193 MPa). Biocompatibility and lack of toxic effect give both composites a perspective for osteoplastic application, but composites doped with ZnONPs are more attractive.

Metal ions doping effect on the physicochemical, antimicrobial, and wound healing profiles of alginate-based composite.

The alginate (Alg) matrix with immobilized hydroxyapatite (HAp) and zinc oxide (ZnO), cross-linked by chitosan (CS) and metal ions (Men+) Ca2+, Zn2+, and Cu2+ was created as a wound dressing. The effect of Men+ and their concentrations on water vapor transition, fluid handling, dehydration, drug release, and healing are shown. Me-containing samples have a lower sorption capacity, than a commercial Kaltostat, however, a much lower degree of their dehydration provides a longer wound wet. The Men+ presence lowers the environmental pH to slightly acidic values promoting healing. Ca2+, Zn2+, and Cu2+ in complexes with CS increase antimicrobial effect against E. coli and S. aureus, slow down the Anaesthesine release, making it compatible with Fickian diffusion in the Zn2+ and Cu2+ presence, and non-Fickian transport under Ca2+ influence. The material promotes the proliferation of the fibroblasts, an increase of collagen fibres, and new arterial and venous capillaries, indicating the intensity of the healing process.

Hydroxyapatite-biopolymers-ZnO composite with sustained Ceftriaxone release as a drainage system for treatment of purulent cavities.

Composite based on nano-sized hydroxyapatite (HA), zinc oxide (ZnO), chitosan (CS), alginate (Alg) with the function of sustained Ceftriaxone (CF) release was created as molecular sorption-aspiration drainage system (SADS), designed for the treatment of purulent cavities of various genesis, including peritonitis. ZnO stabilizes the composite structurally, reducing the swelling by 1.5 and porosity by 1.4 times. The absorption of tryptophan (Trp) by SADS for 72 h from aqueous solution is 80%, while from PBS - 50%. The content of ZnO (15,20%) slows the CF release by 1.6 times on the first day of SADS installation and reduces the likelihood of "burst" drug release. CF release exponent of ZnO-containing composites indicates the non-Fickian diffusion kinetics. 20%ZnO-containing composite is closest to zero-order kinetics. The reduction of the concentration of E. coli microbial cells for 43% in the presence of HA-nZnO-Alg/CS -based CADS and positive therapeutic pathomorphosis were observed in vivo.