Brushite: Synthesis, Properties, and Biomedical Applications

*Khalil Issa, Abdulaziz Alanazi, Khalid A. Aldhafeeri, Ola Alamer and Mazen Alshaaer*

#### **Abstract**

In this chapter, besides its biomedical applications, the synthesis and properties of brushite were investigated. Brushite consists of two types of crystals, platy and needle-like, and their formation depends on the pH of the medium during precipitation. Platy crystals are formed in a slightly acidic medium, pH = 5, and needle-like crystals at a higher pH = 6.5–7. In this study, the monoclinic brushite crystals were synthesized using dissolution-precipitation reactions. It is found that the brushite crystal growth occurs mainly along the (020) crystallographic plane. The thermogravimetric analysis confirms the presence of the two structural water molecules, which decompose at a temperature range between 80 and 220°C. Brushite was used in the preparation of tetracalcium phosphate mineral, which is the powder component for calcium phosphate cement (CPC). CPC was subsequently prepared from TTCP and phosphate-based hardening solution. *In vitro* evaluation of the resultant CPC using Hanks' Balanced Salt Solution results in the growth of nanofibrous crystals of Calcium-deficient hydroxyapatite (CDHA) layers on the surfaces of the CPC. The cultured CPC exhibits new connective tissues and throughout the CaP matrix.

**Keywords:** brushite, hydroxyapatite, tetracalcium phosphates, bioactivity, porosity

#### **1. Introduction**

Calcium phosphates (CaP) are one of the most important compounds found in nature [1, 2]. There are many applications for these compounds in various fields, especially agricultural, environmental, and medical applications. CaP are characterized by their wide diversity as it is produced at different temperatures and pH ranges. In addition, the molar ratio of calcium to phosphorous in the precursors plays an important role in the resulting materials. The biochemical characteristics and mineralogical structures of CaP are similar to inorganic constituents of mammals' bones [3, 4]. Because of their excellent biocompatibility, high bioactivity, and low toxicity, CaP are considered as a good candidate for bone tissue engineering applications. The CaP minerals such as hydroxyapatite, brushite, tricalcium phosphates (TCP) are used as precursors for the preparation of bone cements and bio-ceramics [5, 6]. Therefore, these minerals are widely used for biomedical applications such as drug delivery and bone tissue engineering (**Table 1**) [6–9].

CaP belong to the family of apatite. There are several CaP phases, the most ubiquitous being hydroxyapatite [HAp, Ca10(PO4)6(OH)2]. Other CaP structures include brushite (DCPD, CaHPO4·2H2O) and tricalcium phosphate


*[a] In aqueous solution, [b] These compounds cannot be precipitated from aqueous solutions. [c] Cannot be measured precisely. However, the following values were reported: 25.7 ± 0.1 (pH 7.40), 29.9 ± 0.1 (pH 6.00), and 32.7 ± 0.1 (pH 5.28). [d] Stable at temperatures above 100°C.*

#### **Table 1.**

*List of main phases of CaP [6–9].*

(TCP, Ca3(PO4)2). Several low- and high-temperature approaches have been reported for synthesizing HAp and brushite (DCPD), while TCP is primarily synthesized using high-temperature methods [6]. The chemical formation of CaP minerals is common in natural systems, although the elucidation of the mechanisms of formation and transformations between the crystal forms of the minerals remains a major challenge. The most thermodynamically stable form, at ambient temperature and pressure, is calcium hydroxyapatite (HAp); however, this does not form readily without a transition phase. Other mineral phases, such as octacalcium phosphate (OCP) and amorphous TCP, are precursor phases that can transform to HAp [10].

Acidic CaP, such as brushite (dicalcium phosphate dehydrate, DCPD), are thermodynamically unstable under pH values greater than 6–7 and thus undergo transformation into more stable CaP. Researchers have also demonstrated that meta-stable brushite (DCPD) may convert to OCP or calcium hydroxyapatite (HAp), and that OCP may convert to hydroxyapatite, depending on the Ca/P ratio and the pH value of the setting reactions [11]. Brushite, a type of CaP that is the most easily synthesized, transforms into monetite (dicalcium phosphate anhydrate, DCPA) at temperatures above 80°C. Monetite (DCPA) is the anhydrous form of brushite (DCPD) and can, like brushite, be crystallized from aqueous solutions, but only when the temperature is above 80°C. At low pH values (<7), monetite is the most stable of the CaP, although the conversion of brushite to monetite is faster when the water is warmer and more acidic [8].

Brushite-based biomaterials are characterized by good bioactivity, and they are bioresorbable and biocompatible. Unlike apatite-based materials, brushite-based

#### *Brushite: Synthesis, Properties, and Biomedical Applications DOI: http://dx.doi.org/10.5772/intechopen.102007*

ones are rapidly resorbed in vivo [12]. The bioactivity and biocompatibility of brushite-based biomaterials have been investigated in several compositions, applications, and in vivo [11]. Brushite-based materials are biocompatible with and tolerated by soft tissues and bone in vivo, so that material resorption was shortly followed by the formation of new bone tissues. Histological measurements and experimental studies indicate that brushite-based materials feature good biocompatibility, with no appearance of inflammatory cells [12].

Amorphous calcium phosphate (ACP) is often encountered as a transient phase during the formation of CaP in aqueous systems. Usually, ACP is the first phase that is precipitated from a supersaturated solution prepared by the rapid mixing of solutions containing calcium cations and phosphate anions. The chemical composition of ACP strongly depends on the solution's pH value and the concentrations of calcium and phosphate ions. For example, ACP phases are formed with Ca/P ratios in the range of 1.18:1 (precipitated in a solution with a pH value of 6.6) to 1.53:1 (precipitated in a solution with a pH value of 11.7), although ratios of up to 2.5:1 have also been encountered [8]. The structure of ACP is still uncertain and it has been reported to be more soluble than brushite [13]. ACP could be stabilized by another chemical compound: e.g., pyrophosphate (P2O7 4−) retards the conversion of ACP to apatite. Finally, ACP is characterized by its relatively high solubility and ability to obtain a substantial release of Ca2+ and PO4 ions [12].

This chapter aims to synthesis brushite as one of the most common CaP. The microstructural and thermal properties of this mineral are characterized and discussed. After that, the thermochemical transformation of brushite was investigated. The resultant compound is used as precursors for bone cement. Finally, biomineralization and the bioactivity, and biomineralization of calcium phosphate cement (CPC) are studied *in vitro*.
