Osteoclast-Responsive, Injectable Bone of Bisphosphonated-Nanocellulose that Regulates Osteoclast/Osteoblast Activity for Bone Regeneration

An injectable bone may serve as a minimally invasive therapy for large orthopedic defects and osteoporosis and an alternative to allografting and surgical treatment. However, conventional bone substitutes lack the desirable biodegradability, bioresponsibility, and functionality to regulate the bone regeneration process. Here, we report an injectable, bioresponsive bone composed of bisphosphonate-modified nanocellulose (pNC) as a bone substitute for bone regeneration. Composites composed of nanofibrillated cellulose and beta-tricalcium phosphate (beta-TCP) mimic bone structures in which apatite reinforces collagen fibrils. Bisphosphonate groups on nanocellulose provide reversible, physical cross-linking with beta-TCP, apatite formation, binding property to bone, and pH responsiveness. When the pH drops to similar to 4.5, which corresponds to an osteoclast-induced pH decrease, pNC-beta-TCP composite degrades and releases pNC. pNC suppresses osteoclast formation and pit formation. This osteoclast-responsive property allows for controlling the degradation rate of the composite. Moreover, the composite of pNC, alpha-tricalcium phosphate (alpha-TCP), and beta-TCP enhances osteoblast differentiation. This injectable bone substitute of pNC that regulates osteoclast/osteoblast activity has enormous potential for the treatment of bone diseases and prevention of locomotive syndrome.