Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes, and Putties - Calcium Orthophosphates: Applications in Nature, Biology and Medicine - page 479

and larger tensile strengths due to a higher homogeneity. However,
the use of orthophosphoric acid might impair the biocompatibility
of the cement formulation, due to low pH values during setting
[153]. If a cement formulation contains an excess of a basic phase,
the equilibrium pH will be given by the intersection of the solubility
isotherms of the basic phase with that of DCPD. For example, the
equilibrium pH values of β-TCP + MCPM, HA + MCPM, and TTCP +
MCPM mixtures are 5.9, 4.2, and 7.6, respectively [197, 198].
As the solubility of calcium orthophosphates decreases with
increasing of their basicity (Table 1.1 and Fig. 1.6), the setting time of
brushite cements much depends on the solubility of a basic phase: the
higher its solubility, the faster the setting time. Therefore, the setting
time of the cements made of MCPM + a basic calcium orthophosphate
increases in the order: HA > β-TCP > α-TCP [197, 198]. For example,
HA + MCPM mixtures have a setting time of several minutes: β-TCP +
MCPM mixtures—of 30-60 s and α-TCP + MCPM mixtures—of a few
seconds [150, 151]. Follow-up of the chemical composition by

31

P
solid state NMR enabled to show that the chemical setting process for
β-TCP + MCPM formulation appeared to reach an end after ~20 min
[221]. Nevertheless, despite this initial high reactivity, the hardening
reaction of brushite cements typically lasts one day until completion
[207, 208]. Additives that inhibit the crystal growth of DCPD have
been successfully used to increase the setting time of β-TCP + MCPM
mixtures [222]. In contrast to apatite cements, the brushite cements
can be initially liquid and still set within a short period of time [197,
198].
By itself, brushite is remarkably biocompatible and bioresorbable
[220]. Due to both a better solubility of DCPD if compared to that
of CDHA (Table 1.1 and Fig. 1.6) and metastability of DCPD under
physiological conditions [223], after implantation brushite cements
are faster degradable than apatite ones [224-226]. They are quickly
resorbed and suffered from a rapid decrease in strength

(although the mechanical properties of the healing bone increase
as bone ingrowth occurs [35]). Short setting times, low mechanical
strength, and limited injectability seem to prevent brushite cements
from a broader clinical application. However, the major reason why
brushite cements are not more widespread is probably not related
to the mechanical issues but just to a later arrival on the market.
Use of sodium citrate or citric acid as setting retardants is an option

in vivo