Shape-Memory ECM-Mimicking Heparin-Modified Nanofibrous Gelatin Scaffold for Enhanced Bone Regeneration in Sinus Augmentation.

Biomaterials with clinical maneuverability and predictable bone regeneration are needed in the field of maxillary sinus augmentation. Herein, gelatin was chemically modified with heparin that specifically interacted with and stabilized bone morphogenetic protein-2 (BMP-2). We then introduced thermally induced phase separation to form the injectable, shape-memory, highly porous scaffold for bone regeneration in sinus augmentation. The hydrated heparin-modified nanofibrous gelatin scaffolds (NH-GS) were demonstrated with high resilience and shape-memory property, both macroscopically and microscopically, making them injectable scaffolds and expected to be applied in sinus augmentation. This novel scaffold was verified to be biocompatible and an excellent matrix to support cell attachment, proliferation, and infiltration. Further, the growth factor-loaded NH-GS showed sustained release kinetics of BMP-2 through affinity-based scaffold-growth factor interaction, compared with BMP-2 loaded gelatin sponge (GS) and nanofibrous gelatin scaffold (NF). Both in vitro and in vivo experiments demonstrated that the BMP-2-loaded NH-GS exhibited the highest osteogenesis among the other groups. Taken together, this study introduces a new regenerative strategy in maxillary sinus augmentation, which is injectable with a predefined shape and structure and promotes bone regeneration through a more sustained BMP-2 release.