Improving bone defect healing using magnesium phosphate granules with tailored degradation characteristics.

OBJECTIVES: Dental implant placement frequently requires preceding bone augmentation, for example, with hydroxyapatite (HA) or ß-tricalcium phosphate (ß-TCP) granules. However, HA is degraded very slowly in vivo and for ß-TCP inconsistent degradation profiles from too rapid to rather slow are reported. To shorten the healing time before implant placement, rapidly resorbing synthetic materials are of great interest. In this study, we investigated the potential of magnesium phosphates in granular form as bone replacement materials. METHODS: Spherical granules of four different materials were prepared via an emulsion process and investigated in trabecular bone defects in sheep: struvite (MgNH4PO4·6H2O), K-struvite (MgKPO4·6H2O), farringtonite (Mg3(PO4)2) and ß-TCP. RESULTS: All materials except K-struvite exhibited promising support of bone regeneration, biomechanical properties and degradation. Struvite and ß-TCP granules degraded at a similar rate, with a relative granules area of 29% and 30% of the defect area 4 months after implantation, respectively, whereas 18% was found for farringtonite. Only the K-struvite granules degraded too rapidly, with a relative granules area of 2% remaining, resulting in initial fibrous tissue formation and intermediate impairment of biomechanical properties. SIGNIFICANCE: We demonstrated that the magnesium phosphates struvite and farringtonite have a comparable or even improved degradation behavior in vivo compared to ß-TCP. This emphasizes that magnesium phosphates may be a promising alternative to established calcium phosphate bone substitute materials.

Exploring the potential of magnesium oxychloride, an amorphous magnesium phosphate, and newberyite as possible bone cement candidates.

Magnesium phosphate-based bone cements, particularly struvite (MgNH4PO4∙6H2O)-forming cements, have attracted increased scientific interest in recent years because they exhibit similar biocompatibility to hydroxyapatite while degrading much more rapidly in vivo. However, other magnesium-based minerals which might be promising are, to date, little studied. Therefore, in this study, we investigated three magnesium-based bone cements: a magnesium oxychloride cement (Mg3(OH)5Cl∙4H2O), an amorphous magnesium phosphate cement based on Mg3(PO4)2, MgO, and NaH2PO4, and a newberyite cement (MgHPO4·3H2O). Because it is not sufficiently clear from the literature to what extent these cements are suitable for clinical use, all of them were characterized and optimized regarding setting time, setting temperature, compressive strength and passive degradation in phosphate-buffered saline. Because the in vitro properties of the newberyite cement were most promising, it was orthotopically implanted into a partially weight-bearing tibial bone defect in sheep. The cement exhibited excellent biocompatibility and degraded more rapidly compared to a hydroxyapatite reference cement; after 4 months, 18% of the cement was degraded. We conclude that the newberyite cement was the most promising candidate of the investigated cements and has clear advantages over calcium phosphate cements, especially in terms of setting time and degradation behavior.

Ready-To-Use and Rapidly Biodegradable Magnesium Phosphate Bone Cement: In Vivo Evaluation in Sheep.

In clinical practice, hydroxyapatite (HA) cements for bone defect treatment are frequently prepared by mixing a powder component and a liquid component shortly before implantation in the operation theater, which is time-consuming and error-prone. In addition, HA cements are only slightly resorbed, that is, cement residues can still be found in the bone years after implantation. Here, these challenges are addressed by a prefabricated magnesium phosphate cement paste based on glycerol, which is ready-to-use and can be directly applied during surgery. By using a trimodal particle size distribution (PSD), the paste is readily injectable and exhibits a compressive strength of 9-14 MPa after setting. Struvite (MgNH4 PO4 ·6H2 O), dittmarite (MgNH4 PO4 ·H2 O), farringtonite (Mg3 (PO4 )2 ), and newberyite (MgHPO4 ·3H2 O) are the mineral phases present in the set cement. The paste developed here features a promising degradation of 37% after four months in an ovine implantation model, with 25% of the implant area being newly formed bone. It is concluded that the novel prefabricated paste improves application during surgery, has a suitable degradation rate, and supports bone regeneration.

Accelerated bone regeneration through rational design of magnesium phosphate cements.

Results of several studies during past years suggested that magnesium phosphate cements (MPCs) not only show excellent biocompatibility and osteoconductivity, but they also provide improved regeneration capacity due to higher solubility compared to calcium phosphates. These findings also highlighted that chemical similarity of bone substitutes to the natural bone tissue is not a determinant factor in the success of regenerative strategies. The aim of this study was to further improve the degradation speed of MPCs for a fast bone ingrowth within a few months. We confirmed our hypothesis, that decreasing the powder-liquid ratio (PLR) of cement results in an increased content of highly soluble phases such as struvite (MgNH4PO4⋅6H2O) as well as K-struvite (MgKPO4⋅6H2O). Promising compositions with a low PLR of 1 g ml-1 were implanted in partially-loaded tibia defects in sheep. Both cements were partially degraded and replaced by bone tissue after 4 months. The degradation speed of the K-struvite cement was significantly higher compared to the struvite cement, initially resulting in the formation of a cell-rich resorption zone at the surface of some implants, as determined by histology. Overall, both MPCs investigated in this study seem to be promising as an alternative to the clinically well-established, but slowly degrading calcium phosphate cements, depending on defect size and desired degradation rate. Whereas the K-struvite cement might require further modification towards a slower resorption and reduced inflammatory response in vivo, the struvite cement appears promising for the treatment of bone defects due to its continuous degradation with simultaneous new bone formation. STATEMENT OF SIGNIFICANCE: Cold setting bone cements are used for the treatment of bone defects that exceed a critical size and cannot heal on their own. They are applied pasty into the bone defect and harden afterwards so that the shape adapts to the individual defect. Magnesium phosphates such as magnesium ammonium phosphate hexahydrate (struvite) belong to a new class of these cold setting bone cements. They degrade much faster than the clinically established calcium phosphates. In this study, a magnesium phosphate that has hardly been investigated so far was implanted into partially-loaded defects in sheeps: Potassium magnesium phosphate hexahydrate. This showed even faster resorption compared to the struvite cement: after 4 months, 63% of the cement was already degraded.

Biological and mechanical performance and degradation characteristics of calcium phosphate cements in large animals and humans.

Calcium phosphate cements (CPCs) have been used to treat bone defects and support bone regeneration because of their good biocompatibility and osteointegrative behavior. Since their introduction in the 1980s, remarkable clinical success has been achieved with these biomaterials, because they offer the unique feature of being moldable and even injectable into implant sites, where they harden through a low-temperature setting reaction. However, despite decades of research efforts, two major limitations concerning their biological and mechanical performance hamper a broader clinical use. Firstly, achieving a degradation rate that is well adjusted to the dynamics of bone formation remains a challenging issue. While apatite-forming CPCs frequently remain for years at the implant site without major signs of degradation, brushite-forming CPCs are considered to degrade to a greater extent. However, the latter tend to convert into lower soluble phases under physiological conditions, which makes their degradation behavior rather unpredictable. Secondly, CPCs exhibit insufficient mechanical properties for load bearing applications because of their inherent brittleness. This review places an emphasis on these limitations and provides an overview of studies that have investigated the biological and biomechanical performance as well as the degradation characteristics of different CPCs after implantation into trabecular bone. We reviewed studies performed in large animals, because they mimic human bone physiology more closely in terms of bone metabolism and mechanical loading conditions compared with small laboratory animals. We compared the results of these studies with clinical trials that have dealt with the degradation behavior of CPCs after vertebroplasty and kyphoplasty.