Injectable bioactive polymethyl methacrylate–hydrogel hybrid bone cement loaded with BMP-2 to improve osteogenesis for percutaneous vertebroplasty and kyphoplasty

Polymethyl methacrylate (PMMA) bone cement is used in augmenting and stabilizing fractured vertebral bodies through percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP). However, applications of PMMA bone cement are limited by the high elasticity modulus of PMMA, its low biodegradability, and its limited ability to regenerate bone. To improve PMMA bioactivity and biodegradability and to modify its elasticity modulus, we mixed PMMA bone cement with oxidized hyaluronic acid and carboxymethyl chitosan in situ cross-linking hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to achieve novel hybrid cement. These fabricated PMMA–hydrogel hybrid cements exhibited lower setting temperatures, a lower elasticity modulus, and better biodegradability and biocompatibility than that of pure PMMA cement, while retaining acceptable setting times, mechanical strength, and injectability. In addition, we detected release of BMP-2 from the PMMA–hydrogel hybrid cements, significantly enhancing in vitro osteogenesis of bone marrow mesenchymal stem cells by up-regulating the gene expression of Runx2 , Col1 , and OPN . Use of PMMA–hydrogel hybrid cements loaded with BMP-2 on rabbit femoral condyle bone-defect models revealed their biodegradability and enhanced bone formation. Our study demonstrated the favorable mechanical properties, biocompatibility, and biodegradability of fabricated PMMA–hydrogel hybrid cements loaded with BMP-2, as well as their ability to improve osteogenesis, making them a promising material for use in PKP and PVP. Graphic abstract