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Spatial Recombinant Human Bone Morphogenetic Protein 2 Delivery from Hydroxyapatite Scaffolds Sustains Bone
Joo L Ong1, Stefanie M Shiels1,2, Joseph Pearson1,3
1Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA.
Tissue Engineering. Part C, Methods
|May 26, 2022
Summary
Lower doses of bone growth factor (rhBMP2) delivered from hydroxyapatite/collagen scaffolds improved bone regeneration and density in rabbit models. This controlled delivery strategy enhances bone healing without complications associated with higher doses.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Orthopedic Surgery
Background:
- Large bone defect regeneration often requires growth factors like recombinant human bone morphogenetic protein 2 (rhBMP2).
- Supraphysiological rhBMP2 doses, typically used with acellular collagen sponges (ACS), can cause complications.
- Developing scaffolds with controlled growth factor release is crucial for effective bone regeneration.
Purpose of the Study:
- To develop and evaluate a hydroxyapatite/collagen I (HA/Col) scaffold for improved mechanical properties and controlled rhBMP2 delivery.
- To compare the efficacy of varying rhBMP2 dosages delivered from periosteal membranes with HA or HA/Col scaffolds in critical-sized radial defects in rabbits.
- To assess the impact of bone marrow-derived stromal cells (bMSCs) on bone regeneration with the optimized scaffold and growth factor combination.
Main Methods:
- Fabrication of HA/Col scaffolds with open, connected porosity.
- Delivery of rhBMP2 (76 μg or 15 μg) from a periosteal membrane paired with HA or HA/Col scaffolds in rabbit radial defects.
- Comparison with clinical standard (ACS + 76 μg rhBMP2) and inclusion of a bMSC-seeded group.
- Evaluation using microcomputed tomography, histology, histomorphometry, and torsional testing at 8 weeks.
Main Results:
- The HA/Col scaffold with 15 μg rhBMP2 demonstrated significantly higher bone volume and bone mineral density compared to groups using 76 μg rhBMP2.
- Sustained mineralization front ingrowth was observed with lower rhBMP2 doses, unlike the rapid, early mineralization with higher doses.
- No significant differences in torsional strength, stiffness, or failure angle were found across groups; complete defect bridging occurred in all.
- Addition of bMSCs did not improve bone regeneration metrics and reduced bone-implant apposition.
Conclusions:
- Controlled spatial delivery of lower-dose rhBMP2 from periosteally-placed HA/Col scaffolds enhances bone regeneration and density.
- This strategy offers a promising alternative to high-dose rhBMP2, mitigating potential complications.
- The HA/Col scaffold provides a suitable platform for controlled growth factor release, improving bone healing outcomes.
