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Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds

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Abstract

Purpose

In pediatric neurosurgery, decompressive craniectomy and correction of congenital cranial anomalies can result in major cranial defects. Corrective cranioplasty for the repair of these critical-sized defects is not only a cosmetic issue. The limited availability of suitable autogenous bone and the morbidity of donor site harvesting have driven the search for new approaches with biodegradable and bioactive materials. This study aimed to assess the healing of rabbit calvarial critical-sized defects filled with osteogenic material, either with bioactive glass scaffolds or tricalcium phosphate granules in various combinations with adipose stem cells or bone marrow stem cells, BMP-2, BMP-7, or VEGF to enhance osteogenesis.

Methods

Eighty-two bicortical full thickness critical-sized calvarial defects were operated. Five defects were left empty as negative control defects. The remaining 77 defects were filled with solid bioactive glass scaffolds or tricalcium phosphate granules seeded with adipose or bone marrow derived stem cells in combination with BMP-2, BMP-7, or VEGF. The defects were allowed to heal for 6 weeks before histologic and micro-CT analyses.

Results

Micro-CT examination at the 6-week post-operative time point revealed that defects filled with stem cell-seeded tricalcium phosphate granules resulted in new bone formation of 6.0 %, whereas defects with bioactive glass scaffolds with stem cells showed new bone formation of 0.5 to 1.7 %, depending on the growth factor used.

Conclusions

This study suggests that tricalcium phosphate granules combined with stem cells have osteogenic potential superior to solid bioactive glass scaffolds with stem cells and growth factors.

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References

  1. Martin KD, Franz B, Kirsch M et al (2014) Autologous bone flap cranioplasty following decompressive craniectomy is combined with a high complication rate in pediatric traumatic brain injury patients. Acta Neurochir 156:813–824

    Article  PubMed  Google Scholar 

  2. Piitulainen JM, Kauko T, Aitasalo KM et al (2015) Outcomes of cranioplasty with synthetic materials and autologous bone grafts. World Neurosurg 83:708–714

    Article  PubMed  Google Scholar 

  3. Rish BL, Dillon JD, Meirowsky AM et al (1979) Cranioplasty: a review of 1030 cases of penetrating head injury. Neurosurgery 4:381–385

    Article  CAS  PubMed  Google Scholar 

  4. Sanan A, Haines SJ (1979) Repairing holes in the head: a history of cranioplasty. Neurosurgery 40:588–603

    Google Scholar 

  5. Sándor GK, Tuovinen VJ, Wolff J et al (2013) Adipose stem cell (ASC) tissue engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of GMP-level ASCs for bone regeneration. J Oral Maxillofac Surg 71:938–950

    Article  PubMed  Google Scholar 

  6. Ardjomandi N, Duttenhoefer F, Xavier S et al (2015) In vivo comparison of hard tissue regeneration with ovine mesenchymal stem cells processed with either the FICOLL method or the BMAC method. J Craniomaxillofac Surg 43:1177–1183

    Article  CAS  PubMed  Google Scholar 

  7. Feroze AH, Walmsley GG, Choudhri O et al (2015) Evolution of cranioplasty techniques in neurosurgery: historical review, pediatric considerations, and current trends. J Neurosurg 20:1–10

    Article  Google Scholar 

  8. Serlo WS, Ylikontiola LP, Lähdesluoma N et al (2011) Posterior cranial vault distraction osteogenesis in craniosynostosis: estimated increases in intracranial volume. Childs Nerv Syst 27:627–633

    Article  PubMed  Google Scholar 

  9. Wellisz T, Dougherty W, Gross J (1992) Craniofacial applications for the Medpor porous polyethylene flexblock implant. J Craniofac Surg 3:101–107

    Article  CAS  PubMed  Google Scholar 

  10. Moreira-Gonzalez A, Jackson IT, Miyawaki T et al (2003) Clinical outcome in cranioplasty: critical review in long-term follow-up. J Craniofac Surg 14:144–153

    Article  PubMed  Google Scholar 

  11. Vallittu PK (2014) High-aspect ratio fillers: fiber-reinforced composites and their anisotropic properties. Dent Mater 31:1–7

    Article  PubMed  Google Scholar 

  12. Thesleff T, Lehtimäki K, Niskakangas T et al (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68:1535–1540

    Article  PubMed  Google Scholar 

  13. Stieglitz L, Fung C, Murek M et al (2015) What happens to the bone flap; Long-term outcome after reimplantation of cryoconserved bone flaps in a consecutive series of 92 patients. Acta Neurochir 157:275–280

    Article  PubMed  Google Scholar 

  14. Sundseth J, Sundseth A, Berg-Johnsen J et al (2014) Cranioplasty with autologous cryopreserved bone after decompressive craniectomy. Complications and risk factors for developing surgical site infection. Acta Neurochir 156:805–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Velardi F, Amante PR, Caniglia M et al (2006) Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull. Childs Nerv Syst 22:1158–66

    Article  PubMed  Google Scholar 

  16. Mesimäki K, Lindroos B, Törnwall J et al (2009) Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg 38:201–209

    Article  PubMed  Google Scholar 

  17. Sándor GK, Numminen J, Wolff J et al (2014) Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects. Stem Cells Transl Med 3:530–540

    Article  PubMed  PubMed Central  Google Scholar 

  18. Berger M, Probst F, Schwartz C et al (2015) A concept for scaffold-based tissue engineering in alveolar cleft osteoplasty. J Cranio-Maxillofac Surg 43:830–836

    Article  Google Scholar 

  19. Leucht P, Helms JA (2015) Wnt signaling: an emerging target for bone regeneration. J Am Acad Orthop Surg 23:67–68

    Article  PubMed  Google Scholar 

  20. Jan A, Sándor GK, Iera D et al (2006) Hyperbaric oxygen results in an increase in rabbit calvarial critical sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 101:144–149

    Article  Google Scholar 

  21. Fok TC, Jan A, Peel SA et al (2008) Hyperbaric oxygen results in an increase in vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 105:417–422

    Article  Google Scholar 

  22. Lappalainen OP, Korpi R, Haapea M et al (2015) Healing of rabbit calvarial critical-sized defects using autogenous bone grafts and fibrin glue. Childs Nerv Syst 31:581–7

    Article  PubMed  Google Scholar 

  23. Tirkkonen L, Haimi S, Huttunen S et al (2013) Osteogenic medium is superior to growth factors in differentiation of human adipose stem cells towards bone-forming cells in 3D culture. Eur Cell Mater 25:144–158

    CAS  PubMed  Google Scholar 

  24. Jan A, Sándor GK, Brkovic BM et al (2009) Effects of hyperbaric oxygen on grafted and non-grafted on calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 107:157–163

    Article  Google Scholar 

  25. Jan A, Sándor GK, Brkovic BM et al (2010) Effects of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes. Oral Surg Oral Med Oral Pathol Oral Radiol Endodont 109:60–67

    Article  Google Scholar 

  26. Frassanito P, Tamburrini G, Massimi L et al (2015) Post-marketing surveillance of Custom Bone Service implanted in children under 7 years old. Acta Neurochirurg (Wein) 157:115–121

    Article  Google Scholar 

  27. Waselau M, Patrikoski M, Juntunen M et al. (2012) Effects of bioactive glass S53P4 or beta tricalcium phosphate and Bone Morphogenetic Proteins 2 and BMP-7 on osteogenic differentiation of human adipose stem cells. J Tissue Engineering doi:2041731412467789

  28. Bess S, Line BG, Lafage V et al (2014) Does recombinant human bone morphogenetic protein-2 use in adult spinal deformity increase complications and are complications associated with location of rhBMP-2 use? A prospective, multicenter study of 279 consecutive patients. Spine (Phila Pa 1976) 39:233–242

    Article  Google Scholar 

  29. Devine JG, Dettori JR, France JC et al (2012) Brodt E, McGuire RA. The use of rhBMP in spine surgery: is there a cancer risk? Evid Based Spine Care J 3:35–41

    PubMed  PubMed Central  Google Scholar 

  30. Carragee EJ, Chu G, Rohatgi R et al (2013) Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis. J Bone Joint Surg Am 95:1537–1545

    Article  PubMed  Google Scholar 

  31. Skovrlj B, Koehler SM, Anderson PA et al (2015) Association between BMP-2 and carcinogenicity. Spine (Phila Pa 1976) 40:1862–1871

    Article  Google Scholar 

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Acknowledgments

The authors wish to express their sincere gratitude for the financial support provided to this project by the Emil Aaltonen Foundation, Tampere, Finland, the ITI Foundation, Basel, Switzerland (ITI grant number 619–2009), the University of Oulu EVO and VTR Grant Funds, the Academy of Finland (grants number. 268378 and 273571), Sigrid Juselius Foundation and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 336267.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Oulu University Hospital and Medical Research Center, University of Oulu, Oulu, Finland

    Olli-Pekka Lappalainen, Leena P. Ylikontiola & George K. Sándor

  2. Research Group of Medical Imaging, Physics and Technology, Infotech Doctoral Program, University of Oulu, Oulu, Finland

    Sakari Karhula

  3. Department of Diagnostic Radiology, University of Oulu, Oulu, Finland

    Marianne Haapea

  4. BioMediTech, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland

    Laura Kyllönen, Suvi Haimi, Susanna Miettinen & George K. Sándor

  5. Research Group of Medical Imaging, Physics and Technology, Infotech Doctoral Program, Department of Diagnostic Radiology, Medical Research Center, University of Oulu, Oulu, Finland

    Simo Saarakkala

  6. Department of Otolaryngology, Head and Neck Surgery, Oulu University Hospital, Oulu, Finland

    Jarkko Korpi

  7. Department of Children and Adolescents, Division of Pediatric Surgery, Oulu University Hospital, Medical Research Center, PEDEGO Research Center, University of Oulu, Oulu, Finland

    Willy S. Serlo

Authors
  1. Olli-Pekka Lappalainen
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  2. Sakari Karhula
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  3. Marianne Haapea
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  4. Laura Kyllönen
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  6. Susanna Miettinen
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  7. Simo Saarakkala
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  8. Jarkko Korpi
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  9. Leena P. Ylikontiola
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  10. Willy S. Serlo
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  11. George K. Sándor
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Corresponding author

Correspondence to George K. Sándor.

Ethics declarations

The following animal care and experimental protocol received ethical approvals (Decision ESHL-2008-07701/Ym-23) from the Oulu University Hospital Ethical Committee. The study was performed in accordance with the Helsinki Declaration and its later amendments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Lappalainen, OP., Karhula, S., Haapea, M. et al. Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds. Childs Nerv Syst 32, 681–688 (2016). https://doi.org/10.1007/s00381-016-3017-2

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  • DOI: https://doi.org/10.1007/s00381-016-3017-2

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