High-strength, in situ-setting calcium phosphate composite with protein release

The aim of this study was to develop a mechanically-strong calcium phosphate cement (CPC) with protein release. Chitosan was used to strengthen CPC and control protein release. Mass fraction of protein release = mass of released protein/mass of total protein incorporated into the specimen. Flexural strength (mean +/- sd; n = 6) of CPC containing 100 ng/mL of protein increased from 8.0 +/- 1.4 MPa with 0% chitosan, to 19.8 +/- 1.4 MPa with 15% chitosan (p < 0.05). The latter exceeded the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. When the chitosan mass fraction was increased from 0% to 10% and 15%, protein release varied from 0.60 +/- 0.03 to 0.41 +/- 0.04, and to 0.23 +/- 0.07, respectively (p < 0.05). When powder:liquid ratio increased from 2:1 to 3:1 and 4:1, protein release changed from 0.89 +/- 0.10 to 0.41 +/- 0.04, and to 0.23 +/- 0.07, respectively p < 0.05. Therefore, chitosan content and powder:liquid ratio successfully controlled the protein release. The protein release mass fraction, M, was related to CPC porosity P by: M = 16.9 P(4.5). In summary, a mechanically-strong CPC with controlled protein release was formulated. Protein release was proportional to CPC porosity. The in situ-hardening, nano-apatite composite may have potential for bone tissue engineering, especially when both mechanical strength and controlled release of therapeutic/bioactive agents are needed.