Growth of hydroxyapatite coatings on biodegradable polymer microspheres

Mineral-coated microspheres were prepared via a bioinspired, heterogeneous nucleation process at physiological temperature. Poly(d,l-lactide-co-glycolide) (PLG) microspheres were fabricated via a water-in-oil-in-water emulsion method and were mineral-coated via incubation in a modified simulated body fluid (mSBF). X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy with associated energy-dispersive X-ray spectroscopy confirmed the presence of a continuous mineral coating on the microspheres. The mineral grown on the PLG microsphere surface has characteristics analogous to those of bone mineral (termed "bonelike" mineral), with a carbonate-containing hydroxyapatite phase and a porous structure of platelike crystals at the nanometer scale. The assembly of mineral-coated microspheres into aggregates was observed when microsphere concentrations above 0.50 mg/mL were incubated in mSBF for 7 days, and the size of the aggregates was dependent on the microsphere concentration in solution. In vitro mineral dissolution studies performed in Tris-buffered saline confirmed that the mineral formed was resorbable. A surfactant additive (Tween 20) was incorporated into mSBF to gain insight into the mineral growth process, and Tween 20 not only prevented aggregation but also significantly inhibited mineral formation and influenced the characteristics of the mineral formed on the surface of PLG microspheres. Taken together, these findings indicate that mineral-coated PLG microspheres or mineral-coated microsphere aggregates can be synthesized in a controllable manner using a bioinspired process. These materials may be useful in a range of applications, including controlled drug delivery and biomolecule purification.