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Anionic Citrate-Based 3D-Printed Scaffolds for Tunable and Sustained Orthobiologic Delivery to Enhance Tissue
Se-Hwan Lee1, Ruqiang Lu2, Andrew House2
1McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.
Advanced Functional Materials
|February 23, 2026
Summary
A novel 3D-printed scaffold delivers bone morphogenetic protein-2 (BMP-2) effectively at lower doses. This controlled release system enhances orthopedic applications and reduces adverse effects for better bone fusion.
Area of Science:
- Biomaterials Engineering
- Regenerative Medicine
- Orthopedic Surgery
Background:
- Controlled release systems for orthobiologics are crucial for enhancing therapeutic efficacy.
- Adverse effects from burst release of bone morphogenetic protein-2 (BMP-2) limit its clinical use in orthopedics.
- A novel scaffold is needed to localize orthobiologic activity and enable sustained delivery at lower concentrations.
Purpose of the Study:
- To develop and evaluate an anionic citrate-based 3D-printed scaffold for controlled delivery of orthobiologics.
- To assess the scaffold's ability to sequester, localize, and sustain the release of BMP-2.
- To investigate the scaffold's efficacy in promoting bone fusion at reduced BMP-2 doses.
Main Methods:
- Fabrication of a 3D-printed scaffold using an anionic citrate-based polymer and β-tricalcium phosphate (β-TCP).
- In vitro assessment of BMP-2 binding, sustained release, cytocompatibility, and osteogenic gene activation.
- In vivo evaluation in a rabbit posterolateral fusion model to assess bone formation and fusion efficacy.
Main Results:
- The scaffold demonstrated strong BMP-2 binding, sustained release, and cytocompatibility in vitro.
- In vitro studies showed activation of osteogenic gene expression.
- In vivo studies in rabbits showed successful bone fusion at BMP-2 doses approximately 45-fold lower than clinical standards, with localized delivery promoting osteogenic differentiation.
Conclusions:
- The developed citrate-based 3D-printed scaffold provides a safe and effective platform for controlled orthobiologic delivery.
- This technology advances orthopedic regenerative engineering for complex tissue reconstruction, including spinal fusion.
- Localized delivery of BMP-2 via the scaffold significantly reduces required dosage, mitigating adverse effects and improving clinical potential.
