Polymer-Filled Calcium Phosphate Cement: Mechanical Properties and Controlled Release of Growth Factor

Abstract

Novel calcium phosphate cement (CPC) was developed by incorporating pore-forming particulates (porogens) to induce macropores and proteins to stimulate bone growth. A paste was made from CPC powder (0.15 g, equimolar mixture of tetracalcium phosphate and dicalcium phosphate), biodegradable polymer microspheres [0.1 g, volume fraction of 0.6, (0.17 to 0.36) mm in diameter], and 0.062 g of water. Disks for determining diametral tensile strength (DTS) and mass loss were prepared from the paste in a mold at 37 °C. Disks for the release of a protein were similarly prepared using a solution of the protein, and biodegradable polymer microspheres or water-soluble crystals (mannitol or salicylic acid) as porogens. The disks were immersed at 37 °C in an aqueous solution in order to quantify the effects of the solution on DTS and mass loss, as well as the release of the protein into the solution. The initial DTS value for the disks was (6.4 ± 0.9) MPa. The release of the protein from the CPC/porogen disks persisted for at least 300 h. The release rate of Protein A from the CPC/mannitol disks increased with the volume fraction of mannitol crystals. At a fixed volume fraction of porogens, the release rate of TGF-β1 from the CPC/porogen disks increased with the dissolution rate of the porogens. Thus, the release of a protein from composite grafts consisting of CPC and porogens can be modulated by the volume fraction and the dissolution rate of the porogens.