Abstract
While most bone defects can be repaired spontaneously, the healing process can be complicated due to insufficient bone regeneration when osteoporosis occurs. Synthetic materials that intrinsically stimulate bone formation without inclusion of exogenous cells or growth factors represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Herein, we developed a series of hydroxyapatite bioceramics composed of a microwhiskered scaffold (wHA) reinforced with multiple layers of releasable hydroxyapatite nanoparticles (nHA). These novel bioceramics (nwHA) are tunable to optimize the loading amount of nHA for osteoporotic bone formation. The utility of nwHA bioceramics for the proliferation or differentiation of osteoporotic osteoblasts in vitro is demonstrated. A much more compelling response is seen when bioceramics are implanted in critical-sized femur defects in osteoporotic rats, as nwHA bioceramics promote significantly higher bone regeneration and delay adjacent bone loss. Moreover, the nwHA bioceramics loaded with a moderate amount of nHA can induce new bone formation with a higher degree of ossification and homogenization. Two types of osteogenesis inside the nwHA bioceramic pores were discovered for the first time, depending on the direction of growth of the new bone. The current study recommends that these tailored hybrid micro/nanostructured bioceramics represent promising candidates for osteoporotic bone repair.