Porous apatite biocompatible scaffolds for cell technology for the repair of tissue defects in surgery

Abstract

The problem of repair of tissue defects resulting from extensive operative intervention is very important in surgery. Recent years have seen the development of a basically new concept based on the use of stromal stem cells, whose proliferation and differentiation ensure tissue regeneration [1][2][3]. The implementation of this technology requires porous scaffolds for cell cultivation followed by their implantation into a tissue defect. A promising approach is the use of calcium phosphate ceramic scaffolds. The ceramic should be osteoconductive, cause no adverse response of the organism, and ensure the optimal conditions for protein adsorption and adhesion of osteogenic cells [4,5]. These conditions are met by materials based on hydroxyapatite (HA) [1,6,7].In this paper, we report the results of the design of scaffolds as spherical granules and ceramic blocks obtained by molding of granules followed by heat treatment and having specified dimensions and degree of porosity. The materials were tested in vitro and in vivo to demonstrate their biocompatibility and good prospects for application in reparative plastic surgery. EXPERIMENTAL Production of Porous Granules and Ceramic BlocksMaterials based on HA and fluorohydroxyapatite (FHA) containing up to 10 wt % of fluorine with respect to hydroxy groups were studied. Hydroxyapatites were synthesized by the reaction of calcium hydroxide with ammonium hydrogen phosphate and (in the case of FHA synthesis) potassium fluoride [8]. The granules were prepared in a two-phase system. Suspensions of HA and FHA powders with specific surface areas of 5.5 and 3.7 m 2 /g and an agglomerate size of less than 1 µ m were mixed with an aqueous solution of P-11 gelatine (GOST 11293-89) and dispersed in a liquid dispersion medium (vegetable oil with a viscosity of 0.585 Pa s at 25°ë ) using a paddle stirrer at 200-1000 rpm. During 1 min, nearly spherical granules were formed. These granules were separated on a Büchner funnel, washed, dried, and subjected to heat treatment at 1200°ë for 1 h. The 320-to 500-µ m fraction was isolated by screening the granules on a sieving stack and used to produce porous ceramics and in the subsequent in vitro and in vivo experiments. The linear shrinkage of the granules was determined; the openpore content and size distribution were measured (mercury porosimetry, a Quantachrome Autoscan 1 instrument); the granule morphology and microstructure were measured by scanning electron microscopy (a JEOL JSM-35-CF microscope); and the size distribution of granules was determined (a Coulter Counter instrument). Pressing followed by sintering gave porous ceramic blocks containing two pore populations, namely, intragranular and intergranular pores. Biological AssaysThe porous ceramic granules and blocks were tested in vitro and in vivo. In the in vitro experiments, the properties of the ceramic scaffolds were studied on the human fibroblast (HF) model. The HF cell culture (clone no. 1608) was obtained from the collection of cultures of the Medical Genetic Research Cent...

Criteria of Biocompatibility of Materials for Bone Defect Repair

“…for bone defect repair) under the skin of small laboratory animals followed by their morphological analysis in dynamics is a suitable approach to assess their biocompatibility. We carried out a series of experiments for evaluation of biocompatibility and osteoplastic properties of natural and synthetic materials (monophasic, biphasic, and composite) for bone defect repair [2][3][4][5][6]. The aim of this study was to analyze and systematize criteria of biocompatibility of new osteoplastic materials using the model of subcutaneous implantation of these materials to small laboratory animals.…”