Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties

Abstract

Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates (x = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in Ca10Cux(PO4)6(OH)2-2xO2x). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and E. coli, releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against P. aeruginosa. This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu2+ were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment

“…In a typical procedure, metaphysic cancellous bone tissues were collected during hip arthroplasty surgical procedures performed on patients who gave their consent beforehand for the use of their bones for research purposes. Then, they underwent multiple steps of treatment and culture, in order to collect the h-MSCs, as fully detailed by Jacobs et al 45…”

“…In a typical procedure, metaphysic cancellous bone tissues were collected during hip arthroplasty surgical procedures performed on patients who gave their consent beforehand for the use of their bones for research purposes. Then, they underwent multiple steps of treatment and culture, in order to collect the h-MSCs, as fully detailed by Jacobs et al 45 Prior to the cytotoxicity tests, the heterostructured NPs were sterilized by keeping them in an oven at 180 °C for 2 h. Then, h-MSCs cultured in minimum essential medium (MEM) were seeded in a 24-well plate, exposed to the nanopowders with a concentration of 1 mg mL −1 , and incubated at 37 °C for 3 or 7 days. MEM-cultured h-MSCs without powder were used as a control.…”

Application of Copper Nanoparticles in Dentistry

“…In addition, they reported that it had good adherence to bone marrow cells and maintained good cell viability. Therefore, they recommended it as a promising bioceramic for bone substitution and/or prosthesis coatings [ 109 , 110 ]. A study reported using graphene oxide copper nanocomposites for bone regeneration and revealed vascularized new bone formation [ 111 ].…”

Fibroblasts Mediate Ectopic Bone Formation of Calcium Phosphate Ceramics

“…Biphasic calcium phosphate (BCP) ceramics have been proved to promote ectopic bone formation after subcutaneous or muscle pouch implantation in rodents or larger animals (dog, goat, and sheep) [ 5 ]. In this model, BCP ceramics have excellent biocompatibility and osteo-inductive ability [ 6 , 7 ]. In addition, BCP has been reported to regulate the phenotype of macrophage, dendric cell, and T cell to recruit bone marrow mesenchymal stem cells (BMSCs) and enhance osteogenic differentiation of BMSCs [ 2 , 8 ].…”