Anionic Citrate-Based 3D-Printed Scaffolds for Tunable and Sustained Orthobiologic Delivery to Enhance Tissue...

Sustained and controlled release systems for orthobiologics enhance therapeutic efficacy by enabling precise biomolecule delivery. While bone morphogenetic protein-2 (BMP-2) in combination with bone grafts has shown promise in orthopedic applications, adverse effects related to the burst release of supraphysiological doses limit its clinical utility. To address this challenge, a novel anionic citrate-based 3D-printed scaffold was developed designed to sequester and localize orthobiologic activity at the target site, allowing effective delivery at significantly lower concentrations. Composed of an anionic citrate-based polymer and β-tricalcium phosphate (β-TCP), the 3D-printed scaffold features a hierarchical porous structure that enhances protein binding, cell infiltration, and nutrient exchange. Using BMP-2 as a model orthobiologic, in vitro studies confirmed its strong protein binding, sustained release, cytocompatibility, and osteogenic gene activation. Furthermore, in a comprehensive rabbit posterolateral fusion study, the scaffold's localized BMP-2 promoted osteogenic differentiation and bone fusion was demonstrated at doses ≈45-fold lower than current clinical applications. This study advances orthopedic regenerative engineering by providing a safe and effective platform for controlled orthobiologic delivery in complex tissue reconstruction, such as spinal fusion.