Bone regeneration strategy by different sized multichanneled biphasic calcium phosphate granules: In vivo evaluation in rabbit model

Abstract

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.

Osteogenesis of 3D printed macro-pore size biphasic calcium phosphate scaffold in rabbit calvaria

“…28 Larger surface area facilitates more cells to be attached onto scaffolds and bone ingrowth. 29 Several studies have demonstrated that calcium phosphates with larger surface area facilitated nutrient and oxygen delivery that enhanced more cell attachment, proliferation, and differentiation and eventually promoted bone formation. [29][30][31][32][33] The specific surface area of porous scaffold decreases with the increasing pore size, because volume increases faster than surface area.…”

“…29 Several studies have demonstrated that calcium phosphates with larger surface area facilitated nutrient and oxygen delivery that enhanced more cell attachment, proliferation, and differentiation and eventually promoted bone formation. [29][30][31][32][33] The specific surface area of porous scaffold decreases with the increasing pore size, because volume increases faster than surface area. Bashoor-Zadeh et al 34 found that specific surface area of 200 lm pore size was three-fold larger than that of 870 lm by comparing porous b-TCP substitutes of different pore size but constant porosity.…”

Osteoinductivity of Porous Biphasic Calcium Phosphate Ceramic Spheres with Nanocrystalline and Their Efficacy in Guiding Bone Regeneration

“…In clinical applications, Ca-P granules are generally utilized to fill irregular bone cavity defects caused by trauma, tumor, osteoporosis, and so on. , Generally, spherical granules are more suitable for implanting irregular sites than irregular granules, but most of the existing commercial Ca-P granules in clinic (e.g., BAM, Algipore, and Endobone) present irregular or cubic shapes. − Although several previous studies have successfully fabricated Ca-P spherical granules via centrifugal granulation technology, , the porosity of the obtained granules was quite low. It is generally recognized that the interconnected pore structure plays a vital role in determining the bioactivity of the Ca-P ceramics. , Our previous studies have employed gas-foaming and alginate-gelatinizing methods to fabricate porous spherical Ca-P ceramic granules conveniently. , The addition of alginate could decrease the Ca-P ceramic grain size to some extent, but the grain size is still on sub-micron scale. , Nowadays, progress in nanotechnology allows the fabrication of Ca-P nanoceramics.…”

Transformable Carbonate Apatite Chains as a Novel Type of Bone Graft

“…Previous studies regarding granular bone grafts demonstrated that the surface areas of the granules in the defect were crucial in increasing the concentration of cells throughout the defect. [57][58][59][60] Furthermore, to guide various cells involved in osteogenesis and blood vessels to the defect center from existing bone, high granule-existing bone and granule-granule contact areas and inter-and intragranular spaces with suitable sizes were essential. [44,57,58] The inter-and intragranular empty spaces for the penetration of cells and blood vessels.…”