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Adv. Funct. Mater., 05 June 2025 | https://doi.org/10.1002/adfm.202506063
Anionic Citrate-Based 3D-Printed Scaffolds for Tunable and Sustained Orthobiologic Delivery to Enhance Tissue Regeneration
Se-Hwan Lee1, Ruqiang Lu2, Andrew House2, Zizhao Li1,3, Lindsey Hammond Burton4, Katie Josephine Sikes4, Lynn Marie Pezzanite4, Drew William Koch4, Kevin Michael Labus5, Ben Gadomski5, Jeremiah Easley4, Richard Tuan Tran2, Su Chin Heo1,3,6
1McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA, 19104 USA
2Acuitive Technologies, Inc., 50 Commerce Drive, Allendale, NJ, 07401 USA
3Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA, 19104 USA
4Preclinical Surgical Research Laboratory, Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80523 USA
5Orthopedic Bioengineering Research Laboratory, Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80523 USA
6Department of Dentistry, College of Dentistry, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
Corresponding Authors: Richard Tuan Tran, Su Chin Heo
1McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA, 19104 USA
2Acuitive Technologies, Inc., 50 Commerce Drive, Allendale, NJ, 07401 USA
3Department of Bioengineering, University of Pennsylvania, 210 South 33rd Street, Philadelphia, PA, 19104 USA
4Preclinical Surgical Research Laboratory, Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80523 USA
5Orthopedic Bioengineering Research Laboratory, Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80523 USA
6Department of Dentistry, College of Dentistry, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447 Republic of Korea
Corresponding Authors: Richard Tuan Tran, Su Chin Heo
Abstract
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.
논문정보
- Research article
- 2025년 06월 (BRIC 등록일 2025-06-10)
- 국외 연구진
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