Self-setting collagen-calcium phosphate bone cement: mechanical and cellular properties

Calcium phosphate cement (CPC) can conform to complex bone cavities and set in-situ to form bioresorbable hydroxyapatite. The aim of this study was to develop a CPC-collagen composite with improved fracture resistance, and to investigate the effects of collagen on mechanical and cellular properties. A type-I bovine-collagen was incorporated into CPC. MC3T3-E1 osteoblasts were cultured. At CPC powder/liquid mass ratio of 3, the work-of-fracture (mean +/- sd; n = 6) was increased from (22 +/- 4) J/m(2) at 0% collagen, to (381 +/- 119) J/m(2) at 5% collagen (p < or = 0.05). At 2.5-5% of collagen, the flexural strength at powder/liquid ratios of 3 and 3.5 was 8-10 MPa. They matched the previously reported 2-11 MPa of sintered porous hydroxyapatite implants. SEM revealed that the collagen fibers were covered with nano-apatite crystals and bonded to the CPC matrix. Higher collagen content increased the osteoblast cell attachment (p < or = 0.05). The number of live cells per specimen area was (382 +/- 99) cells/mm(2) on CPC containing 5% collagen, higher than (173 +/- 42) cells/mm(2) at 0% collagen (p < or = 0.05). The cytoplasmic extensions of the cells anchored to the nano-apatite crystals of the CPC matrix. In summary, collagen was incorporated into in situ-setting, nano-apatitic CPC, achieving a 10-fold increase in work-of-fracture (toughness) and two-fold increase in osteoblast cell attachment. This moldable/injectable, mechanically strong, nano-apatite-collagen composite may enhance bone regeneration in moderate stress-bearing applications.