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The materials for the repair of bone defects require bone-inductive and bioabsorbable properties. We developed an apatite-coated hyaluronan (ACH) as a bone-regeneration material. To examine the initial behavior of osteoblast-like cells on ACH and its bone-inductive activity, we evaluated the proliferation and differentiation of osteoblast-like cells grown on ACH in vitro, and examined the effect of ACH on bone regeneration in vivo, comparing these with the effects of an atelocollagen sponge (AS). Hyaluronic acid, cross-linked by divinylsulfone, was freeze-dried and formed apatite in simulated body fluid. MC3T3-E1 osteoblast-like cells were cultured on ACH and AS. Alkaline phosphatase activity and osteocalcin mRNA expression increased more in cells grown on ACH than in those grown on AS. In vivo, round defects were created in rat crania and either filled with ACH or AS or left unfilled (sham group). After surgery, the ACH-treated group showed higher levels of bone formation than the other groups. These findings demonstrate that ACH is more effective than AS in promoting in vitro osteoblast-like cell differentiation and bone formation during the repair of bone defects in vivo, indicating that it may be of use in the treatment of various bone defects.

Organic–inorganic hybrids with apatite-forming abilities in physiological environments offer possibilities for building flexible bone-bonding bioactive materials; several functional groups are known to induce apatite nucleation. Here, bioactive organic–inorganic hybrids from κ-carrageenan and λ-carrageenan containing sulfonic groups were prepared. Carrageenan hydrogels were made by cross-linking with CaCl2. The apatite-forming abilities of each kind of carrageenan hydrogel were examined using simulated body fluid (SBF); λ-carrageenan was found to be superior to κ-carrageenan for this purpose. The former swelled significantly in aqueous conditions, releasing a large amount of Ca2+ ions into the SBF, contributing to rapid apatite formation.

Bioactive ceramics are used for bone-repairing owing to attractive features such as direct bone-bonding in living body, because they have the ability to bond directly to bone. However, there is limitation on clinical applications due to their inappropriate mechanical properties performances such as higher brittleness and lower fracture toughness than natural bone. Organic-inorganic hybrids consisting of organic polymer and the apatite would be attractive as novel bioactive bone substitutes with mechanical performances analogous to those of natural bone. We attempted preparation of apatite-polymer hybrids from hyaluronic acid. It has been attractive for bone- and cartilage-repairing materials due to high biological compatibility. The hydroxyl groups in side chains of the hyaluronic acid were bridged by divinylsulfone. Dense films were obtained after drying at ambient pressure, whereas porous specimens were formed by freeze-drying. They were treated with 1 M-CaCI2 aqueous solution for 24 h. Ability of apatite formation on the specimens was examined in vitro using simulated body fluid (SBF, Kokubo solution). The specimens formed the apatite in SBF within 7 d, when they were previously treated with CaCb solution.