3D-printed nanohydroxyapatite/methylacrylylated silk fibroin scaffold for repairing rat skull defects
Open accessAbstract
The repair of bone defects remains a major challenge in the clinic, and treatment requires bone grafts or bone replacement materials. Existing biomaterials have many limitations and cannot meet the various needs of clinical applications. To treat bone defects, we constructed a nanohydroxyapatite (nHA)/methylacrylylated silk fibroin (MASF) composite biological scaffold using photocurable 3D printing technology. In this study, scanning electron microscopy (SEM) was used to detect the changes in the morphological structure of the composite scaffold with different contents of nanohydroxyapatite, and FTIR was used to detect the functional groups and chemical bonds in the composite scaffold to determine the specific components of the scaffold. In in vitro experiments, bone marrow mesenchymal stem cells from SD rats were cocultured with scaffolds soaking solution, and the cytotoxicity, cell proliferation, Western blot analysis, Quantitative real-time PCR analysis, bone alkaline phosphatase activity and alizarin red staining of scaffolds were detected to determine the biocompatibility of scaffolds and the effect of promoting proliferation and osteogenesis of bone marrow mesenchymal stem cells in vitro. In the in vivo experiment, the skull defect was constructed by adult SD rats, and the scaffold was implanted into the skull defect site. After 4 weeks and 8 weeks of culture, the specific osteogenic effect of the scaffold in the skull defect site was detected by animal micro-CT, hematoxylin and eosin (HE) staining and Masson's staining. Through the analysis of the morphological structure of the scaffold, we found that the frame supported good retention of the lamellar structure of silk fibroin, when mixed with nHA, the surface of the stent was rougher, the cell contact area increased, and cell adhesion and lamellar microstructure for cell migration and proliferation of the microenvironment provided a better space. FTIR results showed that the scaffold completely retained the β -folded structure of silk fibroin, and the scaffold composite was present without obvious impurities. The staining results of live/dead cells showed that the constructed scaffolds had no significant cytotoxicity, and thw CCK-8 assay also showed that the constructed scaffolds had good biocompatibility. The results of osteogenic induction showed that the scaffold had good osteogenic induction ability. Moreover, the results also showed that the scaffold with a MASF: nHA ratio of 1: 0.5 (SFH) showed better osteogenic ability. The micro-CT and bone histometric results were consistent with the in vitro results after stent implantation, and there was more bone formation at the bone defect site in the SFH group.This research used photocurable 3D printing technology to successfully build an osteogenesis bracket. The results show that the constructed nHA/MASF biological composite material, has good biocompatibility and good osteogenesis function. At the same time, in the microenvironment, the material can also promote bone defect repair and can potentially be used as a bone defect filling material for bone regeneration applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The nHA/MASF biocomposite exhibits good biocompatibility and excellent osteogenic function.
“The constructed nHA/MASF biocomposite exhibits good biocompatibility and excellent osteogenic function [73].”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [73]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Altman, G. H., Diaz, F., Jakuba, C., Calabro, T., Horan, R. L., Chen, J., Lu, H., Richmond, J., & Kaplan, D. L. (2003) · Biomaterials · doi:10.1016/s0142-9612(02)00353-8 · Cited by 3,458 · see citing works
Giannoudis, P. V., Dinopoulos, H., & Tsiridis, E. (2005) · Injury · doi:10.1016/j.injury.2005.07.029 · Cited by 2,078 · see citing works
Morbidity at Bone Graft Donor Sites
Younger, E. W., & Chapman, M. W. (1989) · Journal of Orthopaedic Trauma · doi:10.1097/00005131-198909000-00002 · Cited by 2,020 · see citing works
Chitosan: A versatile biopolymer for orthopaedic tissue-engineering
Martino, A. C. D., Sittinger, M., & Risbud, M. V. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.03.016 · Cited by 1,638 · see citing works
New Opportunities for an Ancient Material
Omenetto, F. G., & Kaplan, D. L. (2010) · Science · doi:10.1126/science.1188936 · Cited by 1,458 · see citing works
Silk fibroin biomaterials for tissue regenerations
Kundu, B., Rajkhowa, R., Kundu, S. C., & Wang, X. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.043 · Cited by 1,391 · see citing works
Enhanced functions of osteoblasts on nanophase ceramics
Webster, T. J. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00075-2 · Cited by 1,324 · see citing works
Bone substitutes in orthopaedic surgery: from basic science to clinical practice
Campana, V., Milano, G., Pagano, E. D., Barba, M., Cicione, C., Salonna, G., Lattanzi, W., & Logroscino, G. (2014) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-014-5240-2 · Cited by 1,118 · see citing works
The Biology of Bone Graft Repair
Burchardt, H. (1983) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-198304000-00005 · Cited by 1,085 · see citing works
Surprising strength of silkworm silk
Shao, Z., & Vollrath, F. W. (2002) · Nature · doi:10.1038/418741a · Cited by 1,005 · see citing works
Stein, G. S., Lian, J. B., & Owen, T. A. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.13.2210157 · Cited by 931 · see citing works
Osteoblast adhesion on nanophase ceramics
Webster, T. J., Siegel, R. W., & Bizios, R. (1999) · Biomaterials · doi:10.1016/s0142-9612(99)00020-4 · Cited by 927 · see citing works
Structure and Properties of Silk Hydrogels
Kim, U.-J., Park, J. H., Li, C., Jin, H., Valluzzi, R., & Kaplan, D. L. (2004) · Biomacromolecules · doi:10.1021/bm0345460 · Cited by 857 · see citing works
Fine organization of Bombyx mori fibroin heavy chain gene
Zhou, C. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.12.2413 · Cited by 710 · see citing works
Bone-Graft Substitutes: Facts, Fictions, and Applications
Greenwald, A. S., Boden, S. D., Goldberg, V. M., Khan, Y., Laurencin, C. T., & Rosier, R. N. (2001) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200100022-00007 · Cited by 702 · see citing works
The roles of signaling pathways in bone repair and regeneration
Majidinia, M., Sadeghpour, A., & Yousefi, B. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26042 · Cited by 515 · see citing works
Autologous Bone Graft: Properties and Techniques
Pape, H., Evans, A., & Kobbe, P. (2010) · Journal of Orthopaedic Trauma · doi:10.1097/bot.0b013e3181cec4a1 · Cited by 418 · see citing works
Biodegradable materials for bone defect repair
Wei, S., Ma, J., Xu, L., Gu, X., & Ma, X. (2020) · Military Medical Research · doi:10.1186/s40779-020-00280-6 · Cited by 412 · see citing works
Role of hydroxyapatite nanoparticle size in bone cell proliferation
Cai, Y., Liu, Y., Yan, W., Hu, Q., Tao, J., Zhang, M., Shi, Z., & Tang, R. (2007) · Journal of Materials Chemistry · doi:10.1039/b705129h · Cited by 407 · see citing works
Three-dimensional nano-HAp/collagen matrix loading with osteogenic cells in organ culture
Du, C., Cui, F. Z., Zhu, X. D., & de Groot, K. (1999) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(19990315)44:4 · Cited by 365 · see citing works
Hydroxyapatite–polymer biocomposites for bone regeneration: A review of current trends
Ramesh, N., Moratti, S. C., & Dias, G. J. (2017) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.33950 · Cited by 361 · see citing works
Hydroxyapatite Based Materials for Bone Tissue Engineering: A Brief and Comprehensive Introduction
Shi, H., Zhou, Z., Li, W., Fan, Y., Li, Z., & Wei, J. (2021) · Crystals · doi:10.3390/cryst11020149 · Cited by 312 · see citing works
Calcium orthophosphate-based biocomposites and hybrid biomaterials
Dorozhkin, S. V. (2009) · Journal of Materials Science · doi:10.1007/s10853-008-3124-x · Cited by 300 · see citing works
Reizabal, A., Costa, C. M., Pérez‐Álvarez, L., Vilas‐Vilela, J. L., & Lanceros-Méndez, S. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202210764 · Cited by 292 · see citing works
Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds
Bhumiratana, S., Grayson, W. L., Castaneda, A., Rockwood, D. N., Gil, E. S., Kaplan, D. L., & Vunjak-Novakovic, G. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2010.12.058 · Cited by 265 · see citing works
Zhou, W. Y., Lee, S. H., Wang, M., Cheung, W. L., & Ip, W. (2007) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-007-3089-3 · Cited by 247 · see citing works
Tripathi, G., & Basu, B. (2011) · Ceramics International · doi:10.1016/j.ceramint.2011.07.012 · Cited by 239 · see citing works
Stabilization of Enzymes in Silk Films
Lu, S., Wang, X., Lü, Q., Hu, X., Uppal, N., Omenetto, F. G., & Kaplan, D. L. (2009) · Biomacromolecules · doi:10.1021/bm800956n · Cited by 213 · see citing works
Interconnected porous hydroxyapatite ceramics for bone tissue engineering
Yoshikawa, H., Tamai, N., Murase, T., & Myoui, A. (2008) · Journal of The Royal Society Interface · doi:10.1098/rsif.2008.0425.focus · Cited by 203 · see citing works
The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds
Yang, X., Yang, F., Walboomers, X. F., Bian, Z., Fan, M., & Jansen, J. A. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32535 · Cited by 201 · see citing works
Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects
Lu, H., Liu, Y., Guo, J., et al. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030334 · Cited by 183 · see citing works
Head and Neck Lymphatic Malformation Treatment
Adams, M. T., Saltzman, B. S., & Perkins, J. A. (2012) · Otolaryngology · doi:10.1177/0194599812453552 · Cited by 177 · see citing works
Tran, H. A., Hoang, T. T., Maraldo, A., Do, T. N., Kaplan, D. L., Lim, K. S., & Rnjak‐Kovacina, J. (2023) · Materials Today · doi:10.1016/j.mattod.2023.03.027 · Cited by 155 · see citing works
Transcription Factor Runx2 and its Application to Bone Tissue Engineering
Carbonare, L. D., Innamorati, G., & Valenti, M. T. (2011) · Stem Cell Reviews and Reports · doi:10.1007/s12015-011-9337-4 · Cited by 143 · see citing works
The Relationship between Secondary Structure and Biodegradation Behavior of Silk Fibroin Scaffolds
Hu, Y., Zhang, Q., You, R., Wang, L., & Li, M. (2012) · Advances in Materials Science and Engineering · doi:10.1155/2012/185905 · Cited by 140 · see citing works
Skeletal tissue engineering using silk biomaterials
MacIntosh, A. C., Kearns, V., Crawford, A., et al. (2008) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.68 · Cited by 126 · see citing works
Liu, Y., Wang, G., Cai, Y., et al. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32192 · Cited by 123 · see citing works
Silk fibroin/hydroxyapatite scaffold: a highly compatible material for bone regeneration
Saleem, M., Rasheed, S., & Yougen, C. (2020) · Science and Technology of Advanced Materials · doi:10.1080/14686996.2020.1748520 · Cited by 113 · see citing works
Nakase, T., Takaoka, K., Hirakawa, K., et al. (1994) · Bone and Mineral · doi:10.1016/s0169-6009(08)80056-6 · Cited by 110 · see citing works
Surface Properties of Silk Fibroin Films and Their Interaction with Fibroblasts
Servoli, E., Maniglio, D., Motta, A., et al. (2005) · Macromolecular Bioscience · doi:10.1002/mabi.200500137 · Cited by 109 · see citing works
Diane, U., Yang, F., Long, D., Hao, Z., Dai, J. H., & Zhao, A. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01781 · Cited by 102 · see citing works
Preparation and characterization of nano-hydroxyapatite/silk fibroin porous scaffolds
Liu, L., Liu, J., Wang, M., et al. (2008) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856208783721010 · Cited by 101 · see citing works
Tu, H., Yu, R., Lin, Z., Zhang, L., Lin, N., Yu, W. D., & Liu, X. (2016) · Advanced Functional Materials · doi:10.1002/adfm.201603403 · Cited by 100 · see citing works
Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials
Farokhi, M., Aleemardani, M., Solouk, A., Mirzadeh, H., Teuschl, A. H., & Redl, H. (2021) · Biomedical Materials · doi:10.1088/1748-605x/abb615 · Cited by 95 · see citing works
Processing silk hydrogel and its applications in biomedical materials
Wang, H., & Zhang, Y. (2015) · Biotechnology Progress · doi:10.1002/btpr.2058 · Cited by 85 · see citing works
The behavior of aged regenerated Bombyx mori silk fibroin solutions studied by 1H NMR and rheology
Zainuddin, Le, T. T., Park, Y., Chirilă, T. V., Halley, P. J., & Whittaker, A. K. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.07.041 · Cited by 81 · see citing works
Phukan, R. D., Herzog, T. L., Boland, P. J., et al. (2015) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-015-4361-3 · Cited by 76 · see citing works
Szurkowska, K., & Kolmas, J. (2017) · Progress in Natural Science Materials International · doi:10.1016/j.pnsc.2017.08.009 · Cited by 75 · see citing works
Chirilă, T. V., Suzuki, S., & Papolla, C. (2017) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1552 · Cited by 72 · see citing works
Tissue Engineering of Bone by Osteoinductive Biomaterials
Ripamonti, U., & Duneas, N. (1996) · MRS Bulletin · doi:10.1557/s0883769400031833 · Cited by 71 · see citing works
Li, Y., Yu, Z., Ai, F., et al. (2021) · Materials & Design · doi:10.1016/j.matdes.2021.109712 · Cited by 62 · see citing works
Lee, D. H., Tripathy, N., Shin, J. H., Song, J. E., Geun, J., Min, K. D., Park, C. H., & Khang, G. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.11.002 · Cited by 61 · see citing works
Fabrication and Biocompatibility of Electrospun Silk Biocomposites
Wei, K., Kim, B., & Kim, I. S. (2011) · Membranes · doi:10.3390/membranes1040275 · Cited by 60 · see citing works
Repair of rabbit femoral condyle bone defects with injectable nanohydroxyapatite/chitosan composites
Zhang, X., Zhu, L., Lv, H., et al. (2012) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-012-4662-y · Cited by 58 · see citing works
Methacrylated Silk Fibroin Hydrogels: pH as a Tool to Control Functionality
Barroso, I. A., Man, K., Villapún, V. M., Cox, S. C., & Ghag, A. K. (2021) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00791 · Cited by 49 · see citing works
Jaiswal, S., Dubey, A., & Debrupa Lahiri, A. (2019) · Journal of the Indian Institute of Science · doi:10.1007/s41745-019-00124-w · Cited by 45 · see citing works
Hydroxyapatite (HA) bone scaffolds with controlled macrochannel pores
Bae, C., Kim, H., Kim, H.-W., et al. (2006) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-006-8934-2 · Cited by 43 · see citing works
Fang, J., Wang, D., Hu, F., et al. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112354 · Cited by 43 · see citing works
Kamiya, N., & Takagi, M. (2001) · The Histochemical Journal · doi:10.1023/a:1014955925339 · Cited by 38 · see citing works
Ren, M., Wang, X., Hu, M., Jiang, Y., Xu, D., Xiang, H., Lin, J., & Yu, B. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112570 · Cited by 37 · see citing works
Diker, N., Gülsever, S., Köroğlu, T., Akçay, E. Y., & Oğuz, Y. (2018) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000004338 · Cited by 29 · see citing works
Rapid Synthesis of Multifunctional Apatite via the Laser-Induced Hydrothermal Process
Song, S., Um, S., Park, J., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c05110 · Cited by 27 · see citing works
Biphasic ceramic bone graft with biphasic degradation rates
Chang, H., Tuan, W., & Lai, P. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111421 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review
Zhu, S., Zhang, Q., Xu, X., Liu, Z., Cheng, G., Long, D., Cheng, L., & Dai, F. (2025) · Polymers · doi:10.3390/polym17060772 · Cited by 36 · see citing works
“The constructed nHA/MASF biocomposite exhibits good biocompatibility and excellent osteogenic function [73].”
- Authors
- Huiwen, W., Shuai, L., Jia, X., Shihao, D., Kun, W., Runhuai, Y., Haisheng, Q., & Jun, L.
- Affiliations
- Second Affiliated Hospital of Anhui Medical University (CN)
- Anhui Medical University (CN)
- Corresponding author
- Haisheng, Qian
- ORCID
- Venue
- Journal of Biological Engineering
- Published
- 2024-03-21
- Volume
- 18
- Issue
- 1
- Pages
- 22-22
- ISSN
- 1754-1611 (ISSN-L)
- PMC
- PMC10956317
- OpenAlex
- W4393039951
- Cited by
- 19
- References
- 63
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 1
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Biological Engineering (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Natural Science Foundation of Hefei City ((No. 2022041))
- Clinical Research cultivation Program of the Second Affiliated Hospital of Anhui Medical University ((No. 2020LCZD20))
- Research Fund of Anhui Institute of translational medicine ((No. 2022zhyx-C44))
- Basic and Clinical Cooperative Research Promotion Plan of Anhui Medical University ((No. 2020xkjT040))
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- hydroxyapatite nanoparticles, composite scaffolds, 3D printing, skull defect repair, bone regeneration, bone marrow mesenchymal stem cells, osteogenic differentiation, biocompatibility, rat model, bone graft substitutes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
