Strontium-doped hydroxyapatite polysaccharide materials effect on ectopic bone formation

• Published in: PloS one 2017-09, Vol.12 (9), p.e0184663-e0184663
• Main Authors: Ehret, C, Aid-Launais, R, Sagardoy, T, Siadous, R, Bareille, R, Rey, S, Pechev, S, Etienne, L, Kalisky, J, de Mones, E, Letourneur, D, Amedee Vilamitjana, J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Angiogenesis; Animals; Biocompatibility; Bioengineering; Biological activity; Biology and Life Sciences; Biomedical materials; Blood vessels; Bone growth; Bone regeneration; Bone Substitutes - chemistry; Bone Substitutes - pharmacology; Bones; Cell Differentiation - drug effects; Chemical Sciences; Coated Materials, Biocompatible - pharmacology; Composite materials; Computed tomography; Cytotoxicity; Data processing; Defects; Differentiation; Fourier transforms; Growth factors; Health aspects; Human performance; Humans; Hydroxyapatite; Hydroxyapatites; Hydroxyapatites - pharmacology; Implantation; In vitro methods and tests; In vivo methods and tests; Material chemistry; Materials Testing; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Mice; Middle Aged; Mineralization; Neovascularization; Ossification (ectopic); Osteoblastogenesis; Osteoblasts; Osteogenesis; Osteogenesis - drug effects; Osteoid; Osteopontin; Physical Sciences; Physiological aspects; Polymers; Polysaccharides; Prostheses and Implants; Quantitative analysis; Research and Analysis Methods; Saccharides; Stem cells; Strontium; Strontium - pharmacology; Surface Properties; Surgical implants; Tissue engineering; Titanium alloys; Toxicity; Trace elements; X-Ray Microtomography
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184663

Previous studies performed using polysaccharide-based matrices supplemented with hydroxyapatite (HA) particles showed their ability to form in subcutaneous and intramuscular sites a mineralized and osteoid tissue. Our objectives are to optimize the HA content in the matrix and to test the combination of HA with strontium (Sr-HA) to increase the matrix bioactivity. First, non-doped Sr-HA powders were combined to the matrix at three different ratios and were implanted subcutaneously for 2 and 4 weeks. Interestingly, matrices showed radiolucent properties before implantation. Quantitative analysis of micro-CT data evidenced a significant increase of mineralized tissue formed ectopically with time of implantation and allowed us to select the best ratio of HA to polysaccharides of 30% (w/w). Then, two Sr-substitution of 8% and 50% were incorporated in the HA powders (8Sr-HA and 50Sr-HA). Both Sr-HA were chemically characterized and dispersed in matrices. In vitro studies performed with human mesenchymal stem cells (MSCs) demonstrated the absence of cytotoxicity of the Sr-doped matrices whatever the amount of incorporated Sr. They also supported osteoblastic differentiation and activated the expression of one late osteoblastic marker involved in the mineralization process i.e. osteopontin. In vivo, subcutaneous implantation of these Sr-doped matrices induced osteoid tissue and blood vessels formation.