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Amorphous calcium phosphate nanospheres synthesized at 65ºC in an inorganic solution similar to cell culture media. Credit: Tas; UIUC.

What happens when you let titanium plates set in a biomimetic solution of amino acids, salts, glucose, and vitamins?

A. Cuneyt Tas, a visiting scientist at the University of Illinois at Urbana-Champaign, can answer that question—biomineralization.

Titanium alloys are the preferred biomedical substrates for many orthopedic and dental applications because of their durability and strength, but are limited in their bioactivity. Calcium phosphate coatings, however, can improve the integration of titanium implants with existing bone and tissues. Because current methods for generating these coatings present some shortcomings, novel methods are needed to improve the efficacy of calcium phosphate coatings on biomedical implants.

In a new publication in Materials Science and Engineering C, Tas has shown that he can coat titanium with X-ray amorphous calcium phosphate using a simple method. He took alkali-treated titanium plates and incubated them at 37°C in an inorganic formulation of Dulbecco’s Modified Eagle Medium (DMEM), a solution used to support cell culture applications, that did not contain the vitamins, amino acids, and glucose of standard DMEM. However, the solution did contain inorganic salts present in DMEM. Tas explained in an email that the “high purity,” inorganic-only form of DMEM mimics the composition of human blood plasma. Amorphous calcium phosphate coated the titanium plates within a week in DMEM and within 24 hours in the inorganic solution. (Featured image shows amorphous calcium phosphate deposited on titanium in one day in an inorganic solution similar to DMEM at 37ºC. Credit: Tas; UIUC).

Tas explained in an email: “At 37°C there is quite a low driving force for crystallization in this inorganic solution rich in HCO3 and Mg2+ ions, which are both amorphous calcium phosphate stabilizers. This is also why one obtains calcium phosphate nanoprecipitates with a BET surface area of 900 m2/g in a blood plasma-like solution having 27 mM HCO3 when decreasing the incubation temperature of that solution to 4ºC (Materials Science and Engineering C). We found the coating thickness on titanium after one day was about 200 nanometers, and after seven days the coating was about 800 nanometers.”

Amorphous CaP deposited at 37°C on alkali-treated titanium in one day in an inorganic solution similar to DMEM cell culture media. Credit: Tas; UIUC.

In a separate publication in the Journal of Materials Chemistry B, Tas showed that X-ray amorphous calcium phosphate could deposit onto glass slides from an inorganic solution similar to the inorganic composition of DMEM when incubated at 37°C. Amorphous calcium phosphate is a precursor to mineralized hydroxyapatite, the primary component of human bone and teeth. Interestingly, when this inorganic solution was incubated at 65°C with agitation, monodisperse nanospheres of amorphous calcium phosphate formed (see image right and above). The nanospheres are promising for drug delivery applications.

Although previous studies have shown that certain DMEM solutions could coat materials with forms of calcium phosphate, this report is first to document synthesis of amorphous calcium phosphate. Amorphous calcium phosphate is more soluble than hydroxyapatite, making it ideal for biomedical applications.

Update reflects additional input from A.C.Tas.