Three-dimensional polymer coated 45S5-type bioactive glass scaffolds seeded with human mesenchymal stem cells show bone formation in vivo

  • Fabian Westhauser
  • Christian Weis
  • Matthäus Prokscha
  • Leonie A. Bittrich
  • Wei Li
  • Kai Xiao
  • Ulrich Kneser
  • Hans-Ulrich Kauczor
  • Gerhard Schmidmaier
  • Aldo R. Boccaccini
  • Arash MoghaddamEmail author
Tissue Engineering Constructs and Cell Substrates Original Research
Part of the following topical collections:
  1. Tissue Engineering Constructs and Cell Substrates


45S5-type bioactive glasses are a promising alternative to established substitutes for the treatment of bone defects. Because the three-dimensional (3D) structure of bone substitutes is crucial for bone ingrowth and formation, we evaluated the osteoinductive properties of different polymer coated 3D-45S5 bioactive glass (BG) scaffolds seeded with human mesenchymal stem cells (hMSC) in vivo. BG scaffolds coated with gelatin, cross-linked gelatin, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) were seeded with hMSC prior to implantation into severe combined immunodeficiency mice. Newly formed bone was evaluated with histomorphometry and micro-computed tomography. Bone formation was detectable in all groups, whereas the gelatin-coated BG scaffolds showed the best results and should be considered in further studies.

Graphical Abstract


Bone Formation Bioactive Glass PHBV Human Mesenchymal Stem Cell Severe Combine Immunodeficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Tyler Swing for proofreading, Tom Bruckner for the support according the statistical analysis, and Birgit Frey for histomorphometric processing. This study was financed by the research grant of the Center of Orthopedics, Traumatology, and Spinal Cord Injury, Heidelberg University Hospital.


  1. 1.
    Moghaddam A, Zietzschmann S, Bruckner T, Schmidmaier G. Treatment of atrophic tibia non-unions according to ‘diamond concept’: results of one- and two-step treatment. Injury. 2015;46(Suppl 4):S39–50. doi: 10.1016/S0020-1383(15)30017-6.CrossRefGoogle Scholar
  2. 2.
    Miska M, Findeisen S, Tanner M, Biglari B, Studier-Fischer S, Grutzner PA, et al. Treatment of nonunions in fractures of the humeral shaft according to the diamond concept. Bone Joint J B. 2016;98(1):81–7. doi: 10.1302/0301-620X.98B1.35682.CrossRefGoogle Scholar
  3. 3.
    Westhauser F, Zimmermann G, Moghaddam S, Bruckner T, Schmidmaier G, Biglari B, et al. Reaming in treatment of non-unions in long bones: cytokine expression course as a tool for evaluation of non-union therapy. Arch Orthop Trauma Surg. 2015;135:1107–16.CrossRefGoogle Scholar
  4. 4.
    Janicki P, Schmidmaier G. What should be the characteristics of the ideal bone graft substitute? Combining scaffolds with growth factors and/or stem cells. Injury. 2011;42(Suppl 2):S77–81. doi: 10.1016/j.injury.2011.06.014.CrossRefGoogle Scholar
  5. 5.
    Ilharreborde B, Morel E, Fitoussi F, Presedo A, Souchet P, Pennecot GF, et al. Bioactive glass as a bone substitute for spinal fusion in adolescent idiopathic scoliosis: a comparative study with iliac crest autograft. J Pediatr Orthop. 2008;28(3):347–51. doi: 10.1097/BPO.0b013e318168d1d4.CrossRefGoogle Scholar
  6. 6.
    Pernaa K, Koski I, Mattila K, Gullichsen E, Heikkila J, Aho AJ, et al. Bioactive glass S53P4 and autograft bone in treatment of depressed tibial plateau fractures—a prospective randomized 11-year follow-up. J Long Term Eff Med Implant. 2011;21(2):139–48. doi: 10.1615/JLongTermEffMedImplants.v21.i2.40.CrossRefGoogle Scholar
  7. 7.
    Hu S, Chang J, Liu M, Ning C. Study on antibacterial effect of 45S5 Bioglass. J Mater Sci Mater Med. 2009;20(1):281–6. doi: 10.1007/s10856-008-3564-5.CrossRefGoogle Scholar
  8. 8.
    Hoppe A, Guldal NS, Boccaccini AR. A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. Biomaterials. 2011;32(11):2757–74. doi: 10.1016/j.biomaterials.2011.01.004.CrossRefGoogle Scholar
  9. 9.
    Dapunt U, Spranger O, Gantz S, Burckhardt I, Zimmermann S, Schmidmaier G, et al. Are atrophic long-bone nonunions associated with low-grade infections? Ther Clin Risk Manag. 2015;11:1843–52. doi: 10.2147/TCRM.S91532.CrossRefGoogle Scholar
  10. 10.
    Chen QZ, Thompson ID, Boccaccini AR. 45S5 Bioglass-derived glass-ceramic scaffolds for bone tissue engineering. Biomaterials. 2006;27(11):2414–25. doi: 10.1016/j.biomaterials.2005.11.025.CrossRefGoogle Scholar
  11. 11.
    El-Gendy R, Yang XB, Newby PJ, Boccaccini AR, Kirkham J. Osteogenic differentiation of human dental pulp stromal cells on 45S5 Bioglass(R) based scaffolds in vitro and in vivo. Tissue Eng Part A. 2013;19(5–6):707–15. doi: 10.1089/ten.TEA.2012.0112.CrossRefGoogle Scholar
  12. 12.
    Arkudas A, Balzer A, Buehrer G, Arnold I, Hoppe A, Detsch R, et al. Evaluation of angiogenesis of bioactive glass in the arteriovenous loop model. Tissue Eng Part C. 2013;19(6):479–86. doi: 10.1089/ten.TEC.2012.0572.CrossRefGoogle Scholar
  13. 13.
    Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005;26(27):5474–91. doi: 10.1016/j.biomaterials.2005.02.002.CrossRefGoogle Scholar
  14. 14.
    Arabnejad S, Burnett Johnston R, Pura JA, Singh B, Tanzer M, Pasini D. High-strength porous biomaterials for bone replacement: a strategy to assess the interplay between cell morphology, mechanical properties, bone ingrowth and manufacturing constraints. Acta Biomater. 2016;30:345–56. doi: 10.1016/j.actbio.2015.10.048.CrossRefGoogle Scholar
  15. 15.
    Kaur G, Pandey OP, Singh K, Homa D, Scott B, Pickrell G. A review of bioactive glasses: their structure, properties, fabrication and apatite formation. J Biomed Mater Res A. 2014;102(1):254–74. doi: 10.1002/jbm.a.34690.CrossRefGoogle Scholar
  16. 16.
    Westhauser F, Weis C, Hoellig M, Swing T, Schmidmaier G, Weber M-A, et al. Heidelberg-mCT-analyzer: a novel method for standardized microcomputed-tomography-guided evaluation of scaffold properties in bone and tissue research. R Soc Open Sci. 2015;2:150496. doi: 10.1098/rsos.150496.CrossRefGoogle Scholar
  17. 17.
    Kuehlfluck P, Moghaddam A, Helbig L, Child C, Wildemann B, Schmidmaier G. RIA fractions contain mesenchymal stroma cells with high osteogenic potency. Injury. 2015;46(S8):S2–11.Google Scholar
  18. 18.
    Philippart A, Boccaccini AR, Fleck C, Schubert DW, Roether JA. Toughening and functionalization of bioactive ceramic and glass bone scaffolds by biopolymer coatings and infiltration: a review of the last 5 years. Expert Rev Med Devices. 2015;12(1):93–111. doi: 10.1586/17434440.2015.958075.CrossRefGoogle Scholar
  19. 19.
    World Medical A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. doi: 10.1001/jama.2013.281053.CrossRefGoogle Scholar
  20. 20.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement. Cytotherapy. 2006;8(4):315–7. doi: 10.1080/14653240600855905.CrossRefGoogle Scholar
  21. 21.
    Li W, Nooeaid P, Roether JA, Schubert DW, Boccaccini AR. Preparation and characterization of vancomycin releasing PHBV coated 45S5 Bioglass®-based glass–ceramic scaffolds for bone tissue engineering. J Eur Ceram Soc. 2014;34:505–14. doi: 10.1016/j.jeurceramsoc.2013.08.032.CrossRefGoogle Scholar
  22. 22.
    Li W, Wang H, Ding Y, Scheithauer EC, Goudouri O-M, Grunewald A, et al. Antibacterial 45S5 Bioglass®-based scaffolds reinforced with genipin cross-linked gelatin for bone tissue engineering. J Mater Chem B. 2015;3:3367–78.CrossRefGoogle Scholar
  23. 23.
    Brocher J, Janicki P, Voltz P, Seebach E, Neumann E, Mueller-Ladner U, et al. Inferior ectopic bone formation of mesenchymal stromal cells from adipose tissue compared to bone marrow: rescue by chondrogenic pre-induction. Stem Cell Res. 2013;11(3):1393–406. doi: 10.1016/j.scr.2013.07.008.CrossRefGoogle Scholar
  24. 24.
    Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 2010;25(7):1468–86. doi: 10.1002/jbmr.141.CrossRefGoogle Scholar
  25. 25.
    Chang B, Song W, Han T, Yan J, Li F, Zhao L, et al. Influence of pore size of porous titanium fabricated by vacuum diffusion bonding of titanium meshes on cell penetration and bone ingrowth. Acta Biomater. 2016;. doi: 10.1016/j.actbio.2016.01.022.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fabian Westhauser
    • 1
  • Christian Weis
    • 2
  • Matthäus Prokscha
    • 1
  • Leonie A. Bittrich
    • 3
  • Wei Li
    • 4
  • Kai Xiao
    • 1
  • Ulrich Kneser
    • 3
  • Hans-Ulrich Kauczor
    • 2
  • Gerhard Schmidmaier
    • 1
  • Aldo R. Boccaccini
    • 4
  • Arash Moghaddam
    • 1
    Email author
  1. 1.HTRG - Heidelberg Trauma Research Group, Trauma and Reconstructive Surgery, Center of Orthopedics, Traumatology, and Spinal Cord InjuryHeidelberg University HospitalHeidelbergGermany
  2. 2.Clinic of Diagnostic and Interventional Radiology (DIR)Heidelberg University HospitalHeidelbergGermany
  3. 3.Clinic for Hand-, Plastic- and Reconstructive SurgeryBG-Unfallklinik LudwigshafenLudwigshafen am RheinGermany
  4. 4.Institute of BiomaterialsUniversity of Erlangen-NurembergErlangenGermany

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