The use of injectable sonication-induced silk hydrogel for VEGF165 and BMP-2 delivery for elevation of the maxillary sinus floor
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Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF(165)) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF(165) and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF(165) (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF(165)/BMP-2 (group V + B) (n = 6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF(165) promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V + B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V + B were larger than those of the Silk gel and VEGF groups, and the V + B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V + B. In conclusion, VEGF(165) and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.
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The result of new bone formation from injectable hydrogels benefits those developing surgeries such as oral implants.
“This result benefits those developing surgeries such as oral implants [79].”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [79]
Injectable hydrogels prepared using ultrasound for sustained release of vascular endothelial growth factor and bone morphogenetic protein-2 showed new bone formation in the maxillary sinus floor of rabbits in the experimental group after injection into the rabbit maxillary sinus floor between the mucous membrane and bone wall for 12 weeks.
“Researchers have prepared injectable hydrogels using ultrasound methods for the sustained release of vascular endothelial growth factor and bone morphogenetic protein-2; animal experiments showed that by injecting into the rabbit’s maxillary sinus floor between the mucous membrane and the bone wall for 12 weeks, there was a new bone formation in the maxillary sinus floor of the rabbits in the”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [79]
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- Authors
- Zhang, W., Wang, X., Wang, S., Zhao, J., Xu, L., Zhu, C., Zeng, D., Chen, J., Zhang, Z., Kaplan, D. L., & Jiang, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Tufts University (US)
- Corresponding author
- Kaplan, David L.
- Jiang, Xinquan
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 32
- Issue
- 35
- Pages
- 9415-9424
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3384686
- OpenAlex
- W2003433953
- Cited by
- 283
- References
- 49
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 10 · 2023: 15 · 2022: 17 · 2021: 20 · 2020: 28 · 2019: 22 · 2018: 25 · 2017: 23 · 2016: 24 · 2015: 24 · 2014: 22 · 2013: 12 · 2012: 15
- FWCI
- 14.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Dalian Institute of Chemical Physics, CAS Institutional Repository (submittedVersion)
- Funders
- National Institutes of Health (DE017207, DE16710, DE21464, EB002520, EB003210)
- National Natural Science Foundation of China (30772431, 30973342)
- Science and Technology Commission of Shanghai Municipality (08410706400, 0952nm04000, 10dz2211600)
- Program for New Century Excellent Talents in University (07SG19, NCET-08-0353)
- Topics
- Health Sciences › Dentistry › Oral Surgery › Dental Implant Techniques and Outcomes
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- injectable bone substitute, maxillary sinus floor elevation, VEGF165, BMP-2, growth factor delivery, angiogenesis, bone formation, bone regeneration, dual growth factor delivery, biodegradable hydrogels, rabbit model
- MeSH terms
- Animals, Fluorescent Dyes, Injections, Male, Maxillary Sinus, Osteogenesis, Rabbits, Sonication, Staining and Labeling, Neovascularization, Physiologic, Hydrogel, Polyethylene Glycol Dimethacrylate, Vascular Endothelial Growth Factor A, Silk, X-Ray Microtomography, Bone Morphogenetic Protein 2, Sinus Floor Augmentation
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