Histomorphometric evaluation of strontium-containing nanostructured hydroxyapatite as bone substitute in sheep

Abstract

The aim of this study is to evaluate the biocompatibility and osteoconductivity in surgical defects of sheep tibias filled with 1% strontium-containing nanostructured hydroxyapatite microspheres (SrHA), stoichiometric hydroxyapatite without strontium microspheres (HA), or blood clots. Santa Ines sheep were subjected to three perforations on the medial side of the left tibia. The biomaterials were characterized by X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) before implantation and by X-Ray Microfluorescence (µFRX) and Scanning Electron Microscopy (SEM) after sheep tibias implantation. Surgical defects were filled with blood clots (control), SrHA (Group 1) or HA (Group 2). After 30 days, 5-µm bone blocks were obtained for histological evaluation, and the blocks obtained from 1 animal were embedded in methylmethacrylate for undecalcified sections. Mononuclear inflammatory infiltrate remained mild in all experimental groups. Giant cells were observed surrounding biomaterials particles of both groups and areas of bone formation were detected in close contact with biomaterials. All groups showed newly formed bone from the periphery to the center of the defects, which the control, HA and SrHA presented 36.4% (± 21.8), 31.2% (± 14.7) and 26.2% (± 12.9) of newly formed bone density, respectively, not presenting statistical differences. In addition, the connective tissue density did not show any significant between groups. The SrHA showing a higher volume density of biomaterial (51.2 ± 14.1) present in the defect compared to HA (32.6 ± 8.5) after 30 days (p = 0.03). Microspheres containing 1% SrHA or HA can be considered biocompatible, have osteoconductive properties and may be useful biomaterials for clinical applications.

Full-Field Strain Analysis of Bone–Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model

“…Therefore, the establishment of a suitable animal model is essential prior to the evaluation of novel biomaterials. The use of ovine models to test new bone grafts has increased over time because of their similarities with humans in weight, bone structure and bone regeneration [34][35][36][37] . Typically, defects are created in a weight-bearing region of the sheep bone, which provides similarities in bone composition, defect size and healing rate compared to humans 36,38 .…”

“…Typically, defects are created in a weight-bearing region of the sheep bone, which provides similarities in bone composition, defect size and healing rate compared to humans 36,38 . Critical defects models generally evaluate the in vivo performance of biomaterials in terms of bone regeneration, remodelling, biomaterial resorption and biological effects 35,39,40 .…”

Alveolar bone repair with strontium- containing nanostructured carbonated hydroxyapatite

“…Among these grafts, HA Ca 10 (PO 4 ) 6 (OH) 2 has been widely used as a bone substitute for approximately 80 years 18 . This ceramic is biocompatible, osteoconductive 15 , similar to the bone and tooth tissue inorganic portions 1 , bioactive, and allows substitutions in its molecular formula and periodic monitoring via imaging because of its radiopacity.…”

Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications

“…As already stated, the bone ECM is composed of inorganic components such as hydroxyapatite crystals, so creating a biomaterial using hydroxyapatite and implanting it into an animal gives the advantage of not having any kind of adverse reactions in addition to perfect fitting. Two combinations of hydroxyapatite materials were found: Sr containing nanostructured hydroxyapatite microspheres (SrHA) compared to stoichiometric hydroxyapatite (HA) microspheres were implanted into a sheep, 56 and Sr substituted hydroxyapatite (Sr-HA) was obtained by adding Sr 2+ ions into a Ca 2+ solution; the appropriate amounts of Sr(NO 3 ) 2 and Ca(NO 3 ) 2 Á4H 2 O were dissolved in order to obtain 8% or 50% (molar ratio) of Ca 2+ substituted by Sr 2+ (8Sr-HA and 50Sr-HA) and further along implanted into mice. 57 Bone cements are usually composed of two systems: powder (homopolymer PMMA (polymethyl methacrylate) + BPO (benzoyl peroxide)/ZrO 2 (zirconia)/BaSO 4 (barium sulphate)); and liquid (monomer MMA + hydroquinone + N,N-dimethyl para-toluidine (DMPT)).…”