Of the in vivo behavior of calcium phosphate cements and glasses as bone substitutes

The use of injectable self-setting calcium phosphate cements or soluble glass granules represent two different strategies for bone regeneration, each with distinct advantages and potential applications. This study compares the in vivo behavior of two calcium phosphate cements and two phosphate glasses with different composition, microstructure and solubility, using autologous bone as a control, in a rabbit model. The implanted materials were alpha-tricalcium phosphate cement (cement H), calcium sodium potassium phosphate cement (cement R), and two phosphate glasses in the P(2)O(5)-CaO-Na(2)O and P(2)O(5)-CaO-Na(2)O-TiO(2) systems. The four materials were osteoconductive, biocompatible and biodegradable. Radiological and histological studies demonstrated correct osteointegration and substitution of the implants by new bone. The reactivity of the different materials, which depends on their solubility, porosity and specific surface area, affected the resorption rate and bone formation mainly during the early stages of implantation, although this effect was weak. Thus, at 4 weeks the degradation was slightly higher in cements than in glasses, especially for cement R. However, after 12 weeks of implantation all materials showed a similar degradation degree and promoted bone neoformation equivalent to that of the control group.     

Biomimetic treatment on dental implants for short-term bone regeneration

Objectives

The main purpose of this work was to assess the short-term bone regenerative potential of new osteoconductive implants. The novelty of the study lies in the analysis of the effectiveness of a novel two-step treatment which combines shot-blasting with a thermo-chemical treatment, at very short times after implant placement in a minipig model.

Materials and methods

Three hundred twenty implants with four different surface treatments, namely bioactivated surfaces, micro-rough grit-blasted, micro-rough acid-etched and smooth as-machined titanium implants were placed into the bone of 20 minipigs. The percent of bone-to-implant contact was determined 3 days, 1, 2, 3 and 10 weeks after implant placement by histomorphometric analysis. Surface composition, topography and wettability of the implant specimens were analysed.

Results

The combination of shot-blasting and thermo-chemical treatment accelerated bone regeneration at early stages in comparison with all other treatments between day 3 and week 3 (p?<?0.05). The value of osseointegration attained at week 2 was maintained until the end of the experiment without any significant changes (percent direct contact?≈?85 %). This was mostly attributed to the ability of these implants to form in vivo a layer of apatitic mineral that coated the implant and could rapidly stimulate bone nucleation and growth from the implant surface.

Conclusions

The surface quality resulting from this treatment on cpTi provided dental implants with a unique ability of rapid bone regeneration and osseointegration.

Clinical relevance

This treatment represents a step forward in the direction of reducing the time prior to implant loading.     

Evaluation of the influence of the addition of biodegradable polymer matrices in the formulation of self-curing polymer systems for biomedical purposes

The solid phase of self-curing formulations of poly(methyl methacrylate) was modified by different biodegradable polymer matrices, such as poly(l-lactic acid), poly(β-hydroxybutyrate) and thermoplastic starches (TPSs). The aim of this modification was the acquisition of a short- to medium-term drug delivery system to release bisphosphonates for hard tissue treatment. Different physico-chemical characterization techniques were used in order to determine the influence of these matrices and their mechanical capacity, in vitro behaviour, curing parameters, residual monomer content and surface topography for the preparation of the self-curing formulations. The incorporation of the polyesters did not induce an increase in water uptake capacity of the system due to their apolar aliphatic character. On the other hand, TPSs exhibited values of water absorption up to 15.3%, related with their hydrophilic chemical structure, dependent on the commercial formulation and the particle size distribution of the powder. The modifications of the solid phase led in all cases to a decrease in the mechanical behaviour of the material, although the formulations modified with TPS were in the range of accepted values according to standard specifications. The immersion of TPS formulations in a simulated physiological environment (phosphate buffer solution, pH 7.4, 37 °C) conducted to a surface porosity related with release of plasticizers of the domains of the biodegradable component of the formulation. Finally drug release capacity was studied by loading the material with Ibandronate, observing high dependence with the kind of TPS added, as well as its particle size.     

Relevance of the setting reaction to the injectability of tricalcium phosphate pastes

The aim of the present work was to analyze the influence of the setting reaction on the injectability of tricalcium phosphate (TCP) pastes. Even if the injection was performed early after mixing powder and liquid, powder reactivity was shown to play a significant role in the injectability of TCP pastes. Significant differences were observed between the injection behavior of non-hardening β-TCP pastes and that of self-hardening α-TCP pastes. The differences were more marked at low liquid-to-powder ratios, using fine powders and injecting through thin needles. α-TCP was, in general, less injectable than β-TCP and required higher injection loads. Moreover, clogging was identified as a mechanism hindering or even preventing injectability, different and clearly distinguishable from the filter-pressing phenomenon. α-TCP pastes presented transient clogging episodes, which were not observed in β-TCP pastes with equivalent particle size distribution. Different parameters affecting powder reactivity were also shown to affect paste injectability. Thus, whereas powder calcination resulted in an increased injectability due to lower particle reactivity, the addition of setting accelerants, such as hydroxyapatite nanoparticles, tended to reduce the injectability of the TCP pastes, especially if adjoined simultaneously with a Na₂HPO₄ solution. Although, as a general trend, faster-setting pastes were less injectable, some exceptions to this rule were found. For example, whereas in the absence of setting accelerants fine TCP powders were more injectable than the coarse ones, in spite of their shorter setting times, this trend was inverted when setting accelerants were added, and coarse powders were more injectable than the fine ones.     

Novel soybean/gelatine-based bioactive and injectable hydroxyapatite foam: material properties and cell response

Despite their known osteoconductivity, clinical use of calcium phosphate cements is limited both by their relatively slow rate of resorption and by rheological properties incompatible with injectability. Bone in-growth and material resorption have been improved by the development of porous calcium phosphate cements. However, injectable formulations have so far only been obtained through the addition of relatively toxic surfactants. The present work describes the response of osteoblasts to a novel injectable foamed bone cement based on a composite formulation including the bioactive foaming agents soybean and gelatine. The foaming properties of both defatted soybean and gelatine gels were exploited to develop a self-hardening soy/gelatine/hydroxyapatite composite foam able to retain porosity upon injection. After setting, the foamed paste produced a calcium-deficient hydroxyapatite scaffold, showing good injectability and cohesion as well as interconnected porosity after injection. The intrinsic bioactivity of soybean and gelatine was shown to favour osteoblast adhesion and growth. These findings suggest that injectable, porous and bioactive calcium phosphate cements can be produced for bone regeneration through minimally invasive surgery.     

Micro‐ and nanostructured hydroxyapatite–collagen microcarriers for bone tissue‐engineering applications

Novel hydroxyapatite (HA)–collagen microcarriers (MCs) with different micro/nanostructures were developed for bone tissue‐engineering applications. The MCs were fabricated via calcium phosphate cement (CPC) emulsion in oil. Collagen incorporation in the liquid phase of the CPC resulted in higher MC sphericity. The MCs consisted of a porous network of entangled hydroxyapatite crystals, formed as a result of the CPC setting reaction. The addition of collagen to the MCs, even in an amount as small as 0.8 wt%, resulted in an improved interaction with osteoblast‐like Saos‐2 cells. The micro/nanostructure and the surface texture of the MCs were further tailored by modifying the initial particle size of the CPC. A synergistic effect between the presence of collagen and the nanosized HA crystals was found, resulting in significantly enhanced alkaline phosphatase activity on the collagen‐containing nanosized HA MCs. Copyright © 2012 John Wiley & Sons, Ltd.     

Calcium phosphate cements: competitive drug carriers for the musculoskeletal system?

This paper attempts to provide an insight in the application of calcium phosphate cements (CPC) in the field of drug delivery devices for the musculoskeletal system. Their ability to set once implanted within the body, giving a highly microporous material, allows incorporation of many types of drugs and biologically active molecules, without losing activity and denaturalization. Additionally, by being injectable these materials can be used in the growing market for new technologies of minimally invasive surgery, and in the treatment of difficult accessible sites. All these characteristics, together with the excellent biological behaviour of CPC, make them good candidates for drug delivery devices to be used in the pharmacological treatment of a great number of diseases of the bone tissue.     

Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration

The application of minimally invasive surgical techniques in the field of orthopaedic surgery has created a growing need for new injectable synthetic materials that can be used for bone grafting. In this work a novel fully synthetic injectable calcium phosphate foam was developed by mixing α-tricalcium phosphate (α-TCP) powder with a foamed polysorbate 80 solution. Polysorbate 80 is a non-ionic surfactant approved for parenteral applications. The foam was able to retain the porous structure after injection provided that the foamed paste was injected shortly after mixing (typically 2.5 min), and set through the hydrolysis of α-TCP to a calcium-deficient hydroxyapatite, thus producing a hydroxyapatite solid foam in situ. The effect of different processing parameters on the porosity, microstructure, injectability and mechanical properties of the hydroxyapatite foams was analysed, and the ability of the pre-set foam to support osteoblastic-like cell proliferation and differentiation was assessed. Interestingly, the concentration of surfactant needed to obtain the foams was lower than that considered safe in drug formulations for parenteral administration. The possibility of combining bioactivity, injectability, macroporosity and self-setting ability in a single fully synthetic material represents a step forward in the design of new materials for bone regeneration compatible with minimally invasive surgical techniques.     

Surface characterization and cell response of a PLA/CaP glass biodegradable composite material

Silicate-based filling materials were designed to obtain new endodontic sealers and root-end filling materials with adequate workability and consistency. Four different formulations (TC, TC 1%, TCf 1%, and TCf) were prepared incorporating calcium chloride as accelerant agent. A plasticizing compound (phyllosilicate) was added to TC 1% and TCf 1%. TC and TC 1% were prepared with water, whereas TCf and TCf 1% were mixed with a latex polymer as fluidizing agent. The aim of this study was to assess the in vitro biological compatibility of designed materials. White-MTA and AH Plus were tested as reference materials. Human osteoblast-like Saos-2 cells were challenged in short-term cultures (72 h) with solid materials and with material extracts in culture medium, and cell viability and number, cellular adhesion, and morphology were assessed. The new cements exerted no acute toxicity in the assay systems. Saos-2 like cells adhered and proliferated on solid samples of the experimental cements and MTA whilst AH Plus did not allowed cell growth. The extracts from the latex-containing cements showed some toxicity. By SEM analysis, osteoblast-like cells appeared adherent and spread on the new materials, and showed the maintenance of polygonal osteoblastic phenotype. Similar morphology was observed for cells on MTA, whereas only few cells were noted on the AH Plus surface. In conclusion, the new materials proved non toxic and supported the growth of bone-like cells, and resulted suitable to be used as endodontic sealers and root-end filling materials.