Hydroxyapatite or Fluorapatite—Which Bioceramic Is Better as a Base for the Production of Bone Scaffold?—A Comprehensive Comparative Study

Abstract

Hydroxyapatite (HAP) is the most common calcium phosphate ceramic that is used in biomedical applications, e.g., as an inorganic component of bone scaffolds. Nevertheless, fluorapatite (FAP) has gained great attention in the area of bone tissue engineering in recent times. The aim of this study was a comprehensive comparative evaluation of the biomedical potential of fabricated HAP- and FAP-based bone scaffolds, to assess which bioceramic is better for regenerative medicine applications. It was demonstrated that both biomaterials had a macroporous microstructure, with interconnected porosity, and were prone to slow and gradual degradation in a physiological environment and in acidified conditions mimicking the osteoclast-mediated bone resorption process. Surprisingly, FAP-based biomaterial revealed a significantly higher degree of biodegradation than biomaterial containing HAP, which indicated its higher bioabsorbability. Importantly, the biomaterials showed a similar level of biocompatibility and osteoconductivity regardless of the bioceramic type. Both scaffolds had the ability to induce apatite formation on their surfaces, proving their bioactive property, that is crucial for good implant osseointegration. In turn, performed biological experiments showed that tested bone scaffolds were non-toxic and their surfaces promoted cell proliferation and osteogenic differentiation. Moreover, the biomaterials did not exert a stimulatory effect on immune cells, since they did not generate excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS), indicating a low risk of inflammatory response after implantation. In conclusion, based on the obtained results, both FAP- and HAP-based scaffolds have an appropriate microstructure and high biocompatibility, being promising biomaterials for bone regeneration applications. However, FAP-based biomaterial has higher bioabsorbability than the HAP-based scaffold, which is a very important property from the clinical point of view, because it enables a progressive replacement of the bone scaffold with newly formed bone tissue.

Analysis of In Vitro Leukocyte Responses to Biomaterials in the Presence of Antimicrobial Porcine Neutrophil Extract (AMPNE)

“…Contact with HAP or FAP did not evoke a significant neutrophil response. A previous report indicated that HAP and FAP did not generate a serious pro-inflammatory response from immune cells in vitro [ 4 ].…”

“…Briefly, biomaterials were made of a polymeric chitosan–agarose phase (both biopolymers were purchased from Sigma-Aldrich Chemicals, Warsaw, Poland) and mineral phase in the form of either hydroxyapatite nanopowder (Sigma-Aldrich Chemicals, Warsaw, Poland) or fluoroapatite nanopowder. Fluoroapatite was produced according to the procedure described previously [ 4 ]. The mixture of 2% ( w / v ) chitosan (50–190 kDa molecular weight), 5% ( w / v ) agarose (gel point 36 ± 1.5 °C) and 40% ( w / v ) bioceramics (HA or FA nanopowder) were prepared in 2% ( v / v ) acetic acid solution (Avantor Performance Materials, Gliwice, Poland).…”

“…However, HA has the tendency toward the fragmentation and release of small particles, which can lead to neutrophil and monocytic cell activation during repair process, which can cause implantation failure [ 1 , 3 ]. While mechanical parameters and the stability of HA are usually improved via the production of composite biomaterials, its biological properties may be significantly modified with various ionic substitutions, e.g., magnesium (Mg 2+ ), silicon (Si 2+ ), zinc (Zn 2+ ), copper (Cu 2+ ), strontium (Sr 2+ ), cobalt (Co 2+ ), lithium (Li + ), or fluoride (F − ) ions [ 4 ]. Recently, fluorapatite (FA), which is produced via the ionic substitution of HA with F − ions, is more often used for bone regeneration and dental applications.…”

“…The organic phase may be of natural (e.g., chitosan, agarose, alginate, collagen, and hyaluronic acid) or synthetic (e.g., poly (glycolic acid) (PGA), polylactic acid (PLA), polycaprolactone (PCL), and polyether ether ketone (PEEK)) origin [ 8 ]. Recently, curdlan, which is a linear bacterial 1,3-β- d -glucan with its unique ability to form a gel after the heating of its aqueous suspension, has been frequently used as a binder for bioceramics during the production of various bone implants and scaffolds [ 4 , 9 ].…”

“…Since it is known that curdlan solution has the ability to activate macrophages and induce inflammatory reactions [ 19 , 20 , 21 ], the goal of this study was also to check whether or not curdlan suspension after heat-induced gelation process retains its pro-inflammatory properties. It should be noted that thermally gelled curdlan more often acts as a binder for bioceramics during biomaterial production [ 4 , 9 ]. It is also the component of a commercially available bone implant called FlexiOss ® (Medical Inventi S.A., Lublin, Poland).…”