Synthetic sticky bone grafts enhance bone regeneration

a preclinical evaluation in rat models

Authors

  • Lei Li Wuhan University. School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology
  • Haojie Lin Wuhan University. School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology
  • Siyu Jin Wuhan University. School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology
  • Shuchang Hu Wuhan University, School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology
  • Wei Sun Wuhan University. School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology
  • Wei Ji Wuhan University. School & Hospital of Stomatology. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration. Key Laboratory of Oral Biomedicine Ministry of Education. Hubei Key Laboratory of Stomatology

DOI:

https://doi.org/10.1590/

Keywords:

Osteogenesis, Bone regeneration, Bone substitutes

Abstract

Objectives  Deproteinized bovine bone minerals (DBBMs) are effective for bone regeneration. However, their limited plasticity can hinder extensive bone defects treatment. This study aimed to develop a composite bone grafting material that is easy to deploy surgically and promotes robust bone regeneration. Methodology  DBBM particles were mixed with a clinical-grade gelatin-based hemostatic gel (w/v ratio of 2/3) to create a composite material referred to as synthetic sticky bone (SSB). Structural properties were assessed using confocal laser scanning microscopy and scanning electron microscopy. To evaluate bone regenerative capacity, 20 male Sprague Dawley rats (eight to ten weeks old) with critical-size jawbone defects were treated with SSB, DBBM, or gelatin gel alone, with an empty defect as a control. Samples were collected at two and four weeks for microcomputed tomography (μCT) analysis of bone volume/total tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and trabecular separation (Tb. Sp). Histological analyses were conducted to examine material remnants and bone formation. Results  SSB showed a binary paste-like composite property with enhanced injectability and plasticity. μCT and histological assessments confirmed that the SSB-treated group had significantly greater new bone formation compared to the DBBM-treated group after four weeks. Conclusions  SSB, which is a paste-like composite of DBBM particles, and a clinical-grade gelatin-based hemostatic gel demonstrated improved structural plasticity and enhanced bone regeneration, offering a promising solution for treating extensive irregular bone defects.

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References

- Dewangan VK, Sampath Kumar TS, Doble M, Daniel Varghese V. Injectable macroporous naturally-derived apatite bone cement as a potential trabecular bone substitute. J Biomed Mater Res B Appl Biomater. 2024;112(3):e35397. doi: 10.1002/jbm.b.35397

» https://doi.org/10.1002/jbm.b.35397

- Sanz M, Ferrantino L, Vignoletti F, Sanctis M, Berglundh T. Guided bone regeneration of non-contained mandibular buccal bone defects using deproteinized bovine bone mineral and a collagen membrane: an experimental in vivo investigation. Clin Oral Implants Res. 2017;28(11):1466-76. doi: 10.1111/clr.13014

» https://doi.org/10.1111/clr.13014

- Kamolratanakul P, Mattheos N, Yodsanga S, Jansisyanont P. The impact of deproteinized bovine bone particle size on histological and clinical bone healing outcomes in the augmented sinus: a randomized controlled clinical trial. Clin Implant Dent Relat Res. 2022;24(3):361-71. doi: 10.1111/cid.13083

» https://doi.org/10.1111/cid.13083

- Kuchler U, Heimel P, Stahli A, Strauss FJ, Luza B, Gruber R. Impact of DBBM fragments on the porosity of the calvarial bone: a pilot study on mice. Materials (Basel). 2020;13(21):4748. doi: 10.3390/ma13214748

» https://doi.org/10.3390/ma13214748

- Simion M, Fontana F, Rasperini G, Maiorana C. Vertical ridge augmentation by expanded-polytetrafluoroethylene membrane and a combination of intraoral autogenous bone graft and deproteinized anorganic bovine bone (Bio Oss). Clin Oral Implants Res. 2007;18(5):620-9. doi: 10.1111/j.1600-0501.2007.01389.x

» https://doi.org/10.1111/j.1600-0501.2007.01389.x

- Saulacic N, Fujioka-Kobayashi M, Kobayashi E, Schaller B, Miron RJ. Guided bone regeneration with recombinant human bone morphogenetic protein 9 loaded on either deproteinized bovine bone mineral or a collagen barrier membrane. Clin Implant Dent Relat Res. 2017;19(4):600-7. doi: 10.1111/cid.12491

» https://doi.org/10.1111/cid.12491

- Buser D, Urban I, Monje A, Kunrath MF, Dahlin C. Guided bone regeneration in implant dentistry: basic principle, progress over 35 years, and recent research activities. Periodontol 2000. 2023;93(1):9-25. doi: 10.1111/prd.12539

» https://doi.org/10.1111/prd.12539

- Zalama E, Karrouf G, Rizk A, Salama B, Samy A. Does zinc oxide nanoparticles potentiate the regenerative effect of platelet-rich fibrin in healing of critical bone defect in rabbits? BMC Vet Res. 2022;18(1):130. doi: 10.1186/s12917-022-03231-6

» https://doi.org/10.1186/s12917-022-03231-6

- Xu J, Gou L, Zhang P, Li H, Qiu S. Platelet-rich plasma and regenerative dentistry. Aust Dent J. 2020;65(2):131-42. doi: 10.1111/adj.12754

» https://doi.org/10.1111/adj.12754

- Diba M, Wang H, Kodger TE, Parsa S, Leeuwenburgh SC. Highly elastic and self-healing composite colloidal gels. Adv Mater. 2017;29(11). doi: 10.1002/adma.201604672

» https://doi.org/10.1002/adma.201604672

- Bertsch P, Diba M, Mooney DJ, Leeuwenburgh SCG. Self-Healing Injectable Hydrogels for tissue regeneration. Chem Rev. 2023;123(2):834-73. doi: 10.1021/acs.chemrev.2c00179

» https://doi.org/10.1021/acs.chemrev.2c00179

- Chen K, Ying Q, Hao X, Sun K, Wang H. Elastic and stretchable double network hydrogel as printable ink for high-resolution fabrication of ionic skin. Int J Bioprint. 2021;7(3):377. doi: 10.18063/ijb.v7i3.377

» https://doi.org/10.18063/ijb.v7i3.377

- Kang JI, Park KM. Advances in gelatin-based hydrogels for wound management. J Mater Chem B. 2021;9(6):1503-20. doi: 10.1039/d0tb02582h

» https://doi.org/10.1039/d0tb02582h

- Liu G, Guo Y, Zhang L, Wang X, Liu R, Huang P, et al. A standardized rat burr hole defect model to study maxillofacial bone regeneration. Acta Biomater. 2019;86:450-64. doi: 10.1016/j.actbio.2018.12.049

» https://doi.org/10.1016/j.actbio.2018.12.049

- Wei J, Chen X, Xu Y, Shi L, Zhang M, Nie M, et al. Significance and considerations of establishing standardized critical values for critical size defects in animal models of bone tissue regeneration. Heliyon. 2024;10(13):e33768. doi: 10.1016/j.heliyon.2024.e33768

» https://doi.org/10.1016/j.heliyon.2024.e33768

- Stavropoulos A, Kostopoulos L, Nyengaard JR, Karring T. Deproteinized bovine bone (Bio-Oss) and bioactive glass (Biogran) arrest bone formation when used as an adjunct to guided tissue regeneration (GTR): an experimental study in the rat. J Clin Periodontol. 2003;30(7):636-43. doi: 10.1034/j.1600-051x.2003.00093.x

» https://doi.org/10.1034/j.1600-051x.2003.00093.x

- Rosner BA. Fundamentals of biostatistics. 6th. Belmont, CA: Thomson-Brooks/Cole; c2006.

- Ozaki M, Takayama T, Yamamoto T, Ozawa Y, Nagao M, Tanabe N, et al. A collagen membrane containing osteogenic protein-1 facilitates bone regeneration in a rat mandibular bone defect. Arch Oral Biol. 2017;84:19-28. doi: 10.1016/j.archoralbio.2017.09.005

» https://doi.org/10.1016/j.archoralbio.2017.09.005

- Ji W, Kerckhofs G, Geeroms C, Marechal M, Geris L, Luyten FP. Deciphering the combined effect of bone morphogenetic protein 6 and calcium phosphate on bone formation capacity of periosteum derived cell-based tissue engineering constructs. Acta Biomater. 2018;80:97-107. doi: 10.1016/j.actbio.2018.09.046

» https://doi.org/10.1016/j.actbio.2018.09.046

- Bolander J, Geris L, Chai Y, Schrooten J, Bloemen V, Ji W. The combined mechanism of bone morphogenetic protein- and calcium phosphate-induced skeletal tissue formation by human periosteum derived cells. Eur Cell Mater. 2016;31:11-25. doi: 10.22203/eCM.v031a02

» https://doi.org/10.22203/eCM.v031a02

- Zhu J, Zhang S, Jin S, Huang C, Shi B, Chen Z, et al. Endochondral repair of jawbone defects using periosteal cell spheroids. J Dent Res. 2024;103(1):31-41. doi: 10.1177/00220345231205273

» https://doi.org/10.1177/00220345231205273

- Ji W, Yang F, Ma J, Bouma MJ, Boerman OC, Chen Z, et al. Incorporation of stromal cell-derived factor-1alpha in PCL/gelatin electrospun membranes for guided bone regeneration. Biomaterials. 2013;34(3):735-45. doi: 10.1016/j.biomaterials.2012.10.016

» https://doi.org/10.1016/j.biomaterials.2012.10.016

- Zhou J, Xiong S, Liu M, Yang H, Wei P, Yi F, et al. Study on the influence of scaffold morphology and structure on osteogenic performance. Front Bioeng Biotechnol. 2023;11:1127162. doi: 10.3389/fbioe.2023.1127162

» https://doi.org/10.3389/fbioe.2023.1127162

- Arokianathan JF, Ramya KA, Janeena A, Deshpande AP, Ayyadurai N, Leemarose A, et al. Non-proteinogenic amino acid based supramolecular hydrogel material for enhanced cell proliferation. Colloids Surf B Biointerfaces. 2020;185:110581. doi: 10.1016/j.colsurfb.2019.110581

» https://doi.org/10.1016/j.colsurfb.2019.110581

- Cheng L, Yao B, Hu T, Cui X, Shu X, Tang S, et al. Properties of an alginate-gelatin-based bioink and its potential impact on cell migration, proliferation, and differentiation. Int J Biol Macromol. 2019;135:1107-13. doi: 10.1016/j.ijbiomac.2019.06.017

» https://doi.org/10.1016/j.ijbiomac.2019.06.017

- Wang H, Zou Q, Boerman OC, Nijhuis AW, Jansen JA, Li Y, et al. Combined delivery of BMP-2 and bFGF from nanostructured colloidal gelatin gels and its effect on bone regeneration in vivo. J Control Release. 2013;166(2):172-81. doi: 10.1016/j.jconrel.2012.12.015

» https://doi.org/10.1016/j.jconrel.2012.12.015

- Ji X, Yuan X, Ma L, Bi B, Zhu H, Lei Z, et al. Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly(epsilon-caprolactone) /nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation. Theranostics. 2020;10(2):725-40. doi: 10.7150/thno.39167

» https://doi.org/10.7150/thno.39167

- Zhang FM, Zhou L, Zhou ZN, Dai C, Fan L, Li CH, et al. Bioactive glass functionalized chondroitin sulfate hydrogel with proangiogenic properties. Biopolymers. 2019;110(12):e23328. doi: 10.1002/bip.23328

» https://doi.org/10.1002/bip.23328

- Wessing B, Lettner S, Zechner W. Guided bone regeneration with collagen membranes and particulate graft materials: a systematic review and meta-analysis. Int J Oral Maxillofac Implants. 2018;33(1):87-100. doi: 10.11607/jomi.5461

» https://doi.org/10.11607/jomi.5461

- He M, Hou Y, Zhu C, He M, Jiang Y, Feng G, et al. 3D-printing biodegradable pu/paam/gel hydrogel scaffold with high flexibility and self-adaptibility to irregular defects for nonload-bearing bone regeneration. Bioconjug Chem. 2021;32(8):1915-25. doi: 10.1021/acs.bioconjchem.1c00322

» https://doi.org/10.1021/acs.bioconjchem.1c00322

- Somaiah C, Kumar A, Mawrie D, Sharma A, Patil SD, Bhattacharyya J, et al. Collagen promotes higher adhesion, survival and proliferation of mesenchymal stem cells. PLoS One. 2015;10(12):e0145068. doi: 10.1371/journal.pone.0145068

» https://doi.org/10.1371/journal.pone.0145068

- Jha AK, Xu X, Duncan RL, Jia X. Controlling the adhesion and differentiation of mesenchymal stem cells using hyaluronic acid-based, doubly crosslinked networks. Biomaterials. 2011;32(10):2466-78. doi: 10.1016/j.biomaterials.2010.12.024

» https://doi.org/10.1016/j.biomaterials.2010.12.024

- Zhai X, Ruan C, Shen J, Zheng C, Zhao X, Pan H, et al. Clay-based nanocomposite hydrogel with attractive mechanical properties and sustained bioactive ion release for bone defect repair. J Mater Chem B. 2021;9(10):2394-406. doi: 10.1039/d1tb00184a

» https://doi.org/10.1039/d1tb00184a

- Lee EJ, Jain M, Alimperti S. Bone microvasculature: stimulus for tissue function and regeneration. Tissue Eng Part B Rev. 2021;27(4):313-29. doi: 10.1089/ten.TEB.2020.0154

» https://doi.org/10.1089/ten.TEB.2020.0154

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Published

2025-06-13

Issue

Vol. 33 (2025)

Section

Original Articles

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Copyright (c) 2025 Lei Li, Haojie Lin, Siyu Jin, Shuchang Hu, Wei Sun, Wei Ji

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How to Cite

Li, L., Lin, H., Jin, S., Hu, S., Sun, W., & Ji, W. (2025). Synthetic sticky bone grafts enhance bone regeneration: a preclinical evaluation in rat models. Journal of Applied Oral Science, 33, e20250108. https://doi.org/10.1590/