Creation of macroporous calcium phosphate cements as bone substitutes by using genipin-crosslinked gelatin microspheres

Macroporous calcium phosphate cements (CPCs) were developed using genipin-crosslinked gelatin microspheres (GMs) with two weight ratios (2.5 wt% and 5 wt%). The initial setting time of the composite was prolonged by GMs. After GMs/CPCs were soaked in phosphate-buffered saline (PBS) for several weeks, macropores appeared as a result of the degradation of GMs. The presence of GMs accelerated the setting reaction and improved the structure of the composite. The compressive strength increased up to 12 MPa (2.5 wt% GMs/CPCs) and 14 MPa (5 wt% GMs/CPCs) after one week of PBS soaking, then gradually decreased to 9 MPa (2.5 wt% GMs/CPCs) and 7 MPa (5 wt% GMs/CPCs) after three weeks of soaking, and further to 6 MPa (2.5 wt% GMs/CPCs) and 2 MPa (5 wt% GMs/CPCs) after five weeks of soaking. CPCs with 2.5 wt% GMs were the most favorable composite in the tested samples. Cell experiments showed that rat osteoblasts displayed normal morphologies when exposed to the 2.5 wt% GMs/CPCs, and proliferation of the cells was also enhanced. An in vivo study showed that new bone tissue was able to grow into the pores that resulted from GM degradation. This study suggests that the new composite could be a promising candidate for use as a bone substitute under non-compression-loaded circumstances.