An axolotl limb regeneration-inspired strategy to enhance alveolar bone regeneration.

Rongpu Liu, Guifang Wang, Li Ma, Guangzheng Yang, Sihan Lin, Ningjia Sun, Jiajia Wang, Huijing Ma, Xinquan Jiang, Wenjie Zhang
Author Information
  1. Rongpu Liu: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  2. Guifang Wang: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  3. Li Ma: Department of Oral Implantology, Pudong New District Oculopathy Odontopathy Dispensary, Shanghai, China.
  4. Guangzheng Yang: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  5. Sihan Lin: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  6. Ningjia Sun: Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK.
  7. Jiajia Wang: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  8. Huijing Ma: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  9. Xinquan Jiang: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  10. Wenjie Zhang: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1 stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.

Keywords

References

  1. Quintessence Int. 2013 Nov-Dec;44(10):763-71 [PMID: 23878847]
  2. Periodontol 2000. 2024 Feb;94(1):483-509 [PMID: 37681552]
  3. BMC Dev Biol. 2010 Feb 12;10:15 [PMID: 20152028]
  4. Science. 2022 Sep 2;377(6610):eabp9444 [PMID: 36048929]
  5. Nat Genet. 2022 Dec;54(12):1946-1958 [PMID: 36456880]
  6. Int J Oral Sci. 2023 Aug 2;15(1):31 [PMID: 37532700]
  7. J Clin Periodontol. 2019 Jun;46 Suppl 21:103-123 [PMID: 30667525]
  8. Bioact Mater. 2020 Aug 10;6(1):75-83 [PMID: 32817915]
  9. Development. 2021 Feb 8;148(3): [PMID: 33558315]
  10. Adv Sci (Weinh). 2024 Apr;11(13):e2305756 [PMID: 38189598]
  11. Int J Oral Sci. 2022 Jan 25;14(1):5 [PMID: 35078971]
  12. Development. 2020 Jul 31;147(14): [PMID: 32665245]
  13. Acta Biomater. 2022 Nov;153:585-595 [PMID: 36167235]
  14. Periodontol 2000. 2023 Oct;93(1):56-76 [PMID: 37855164]
  15. Eur Cell Mater. 2014 Jan 15;27:1-11; discussion 11-2 [PMID: 24425156]
  16. Cell. 2006 Aug 25;126(4):663-76 [PMID: 16904174]
  17. Nat Rev Mol Cell Biol. 2023 May;24(5):334-354 [PMID: 36922629]
  18. Nat Rev Mol Cell Biol. 2019 Dec;20(12):738-752 [PMID: 31582855]
  19. Nature. 2023 Aug;620(7972):163-171 [PMID: 37495694]
  20. Clin Implant Dent Relat Res. 2023 Jun;25(3):564-574 [PMID: 37130799]
  21. Biomaterials. 2017 Aug;135:85-95 [PMID: 28499127]
  22. Bioact Mater. 2024 Feb 28;35:549-563 [PMID: 38434800]
  23. Curr Opin Cell Biol. 2021 Dec;73:117-123 [PMID: 34521022]
  24. Nanoscale. 2016 Mar 7;8(9):5291-301 [PMID: 26881868]
  25. Front Cell Dev Biol. 2023 Oct 23;11:1277686 [PMID: 37941898]
  26. Signal Transduct Target Ther. 2022 May 11;7(1):155 [PMID: 35538062]
  27. Curr Opin Cell Biol. 2021 Oct;72:54-62 [PMID: 34134013]
  28. Sci Transl Med. 2013 Jun 26;5(191):191ra83 [PMID: 23803705]
  29. Science. 2018 Oct 26;362(6413): [PMID: 30262634]
  30. Dev Cell. 2016 Nov 21;39(4):411-423 [PMID: 27840105]
  31. Periodontol 2000. 2023 Oct;93(1):236-253 [PMID: 37490412]
  32. Adv Sci (Weinh). 2023 Sep;10(25):e2302136 [PMID: 37400369]
  33. Front Physiol. 2023 Mar 07;14:978640 [PMID: 36960156]
  34. Nat Commun. 2023 Oct 10;14(1):6346 [PMID: 37816738]
  35. Genome Biol. 2023 Jan 13;24(1):7 [PMID: 36639687]
  36. Nature. 2018 Nov;563(7732):514-521 [PMID: 30356216]
  37. Blood. 2007 Feb 15;109(4):1422-32 [PMID: 17038530]
  38. Cell. 2024 Sep 19;187(19):5298-5315.e19 [PMID: 39168124]
  39. Sci Adv. 2023 Jan 6;9(1):eadd1541 [PMID: 36608118]
  40. Nat Rev Endocrinol. 2016 Apr;12(4):203-21 [PMID: 26893264]
  41. Trends Genet. 2017 Aug;33(8):553-565 [PMID: 28648452]
  42. Cell. 2011 Jun 24;145(7):1012-22 [PMID: 21703446]
  43. Nat Plants. 2023 Jun;9(6):908-925 [PMID: 37142750]
  44. Biomaterials. 2022 Feb;281:121333 [PMID: 34995904]
  45. J Dent Res. 2016 Mar;95(3):255-66 [PMID: 26608580]
  46. Periodontol 2000. 2023 Oct;93(1):9-25 [PMID: 38194351]
  47. PLoS One. 2013 May 01;8(5):e61352 [PMID: 23658691]
  48. Development. 2001 Aug;128(15):2929-38 [PMID: 11532916]
  49. Compos B Eng. 2024 Aug 15;283: [PMID: 39071449]
  50. Biomaterials. 2015 Jul;56:68-77 [PMID: 25934280]
  51. Cytokine Growth Factor Rev. 2016 Feb;27:43-54 [PMID: 26704296]

Word Cloud

Created with Highcharts 10.0.0boneregenerationbarrierstemenhancecellschannelalveolarosteogenictissuedefectsaxolotllimbsoftosteogenesisBMP-2-enrichedBCSstructuresbiologicalcellstrategyGuidedGBRwidelyappliedimplantdentistryemployingmembranescreatespacepreventinggingivalingrowthHowevermethodcapacityosteoblastslimitingsufficientvolumelargerInspiredabundanttissue-derivedmobilizeddefectmayfacilitatecomprehensivewithinenvironmentdevelopedbiomimeticsystempromoteusingactivategingival-derivedcell-tracingmousemodelPrrx1demonstratedcriticalroleBMP-2-inducedsubcutaneousSequencinghistologicalanalysesrevealedsignificantlyproliferationmigrationAttributableapplicationsmarkedlyimprovedformationbeaglemandibularresultssuggestnovelosteoinductivefunctionswithouttraditionalmembraneregeneration-inspiredAlveolarAxoltolBMP-2ChannelstructurePrrx1+

Similar Articles

Cited By