Calcium phosphate cements loaded with basic fibroblast growth factor: Delivery and in vitro cell response

Abstract

Combining calcium phosphate cements (CPCs) with bioactive molecules improves their bone regeneration potential. Although CPCs are highly osteoconductive, sometimes they have limited biological responses, especially in terms of cell proliferation. Here, we used basic fibroblast growth factor (bFGF) in an α-tricalcium phosphate cement with different initial powder sizes (coarse vs. fine; designated as CPC-C and CPC-F, respectively) and investigated the behavior of bFGF loading and release, as well as the effects on osteoblast responses. bFGF was loaded at 10 μg/ml or 25 μg/ml onto the set form of two types of CPCs, aiming to allow penetration into the pore structure and adsorption onto the cement crystallites. The CPC formulated with fine powder (CPC-F) had higher specific surface area and smaller-sized pores and retained slightly higher amounts of bFGF within the structure. The bFGF release study performed for 3 weeks showed a sustained-release profile; after an initial rapid release over approximately 3 days, further release pattern was almost linear. Compared to CPC-F, CPC-C showed a much faster release pattern. The effects of the bFGF incorporation within CPCs on cellular responses were assessed in terms of cell proliferation using MC3T3-E1 pre-osteoblastic cells. Compared with bFGF-free CPCs (both CPC-C and CPC-F), those containing bFGF stimulated cell proliferation for up to 7 days. An inhibition study of bFGF receptor demonstrated that the improvement of cell proliferation resulted from the role of bFGF released from the CPCs. This study provides beneficial information on improving the biological properties of CPCs by combining them with specific therapeutic molecules, and particularly with bFGF, showing that the cell proliferative ability was significantly stimulated, which may have potential applications for further use in stem cell-based bone tissue engineering.