A Facile One-Stage Treatment of Critical Bone Defects Using a Calcium Sulfate/hydroxyapatite Biomaterial Providing Spatiotemporal Delivery of Bone Morphogenic Protein-2 and Zoledronic Acid
Open accessAbstract
Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2-induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone.
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Calcium deposition increased over time and with increased ZA in the scaffold, consistent with previous studies.
“which is consistent with our present study that the deposits Calcium has increased over time and the amount of ZA in the scaffold has increased (Raina et al., 2020; Demir-Oğuz and Ege, 2021).”
From Osteogenesis Improvement of Gelatin-Based Nanocomposite Scaffold by Loading Zoledronic Acid (2022) · cites this paper as Raina et al., 2020
The Results section on bone mineral deposition reports ongoing mineral deposition, and the 12-week micro-CT results report greater bone volume with ZA when combined with rhBMP-2 (page numbers unavailable). Neither result establishes that calcium deposition increased over time. Table 1 lists a single ZA dose of 10 μg, so the paper does not support an increase with higher ZA amounts in the scaffold. (LLM, conf=0.84)
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- Authors
- Raina, D. B., Matuszewski, L.-M., Vater, C., Bolte, J., Isaksson, H., Lidgren, L., Tägil, M., & Zwingenberger, S.
- Affiliations
- Lund University (SE)
- University Hospital Carl Gustav Carus (DE)
- Corresponding author
- Raina, Deepak Bushan
- ORCID
- Venue
- Science Advances
- Published
- 2020-11-27
- Volume
- 6
- Issue
- 48
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC7695465
- OpenAlex
- W3109229714
- Cited by
- 74
- References
- 43
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 18 · 2023: 10 · 2022: 17 · 2021: 8
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- VINNOVA (2017-00269)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
- Keywords
- critical-size bone defect, rhBMP-2, zoledronic acid, spatiotemporal drug delivery, bone morphogenic proteins, bisphosphonates, bone resorption, fracture callus, mechanical properties, autograft alternative, osteoinduction
- MeSH terms
- Zoledronic Acid, Animals, Biocompatible Materials, Calcium Sulfate, Recombinant Proteins, Sulfates, Rats, Sprague-Dawley, Durapatite, Rats, Bone Morphogenetic Protein 2
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