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Erschienen in: Child's Nervous System 4/2016

19.01.2016 | Original Paper

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

Erschienen in: Child's Nervous System | Ausgabe 4/2016

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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.
Literatur
1.
Zurück zum Zitat 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 156:813–824CrossRefPubMed 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 156:813–824CrossRefPubMed
2.
Zurück zum Zitat Piitulainen JM, Kauko T, Aitasalo KM et al (2015) Outcomes of cranioplasty with synthetic materials and autologous bone grafts. World Neurosurg 83:708–714CrossRefPubMed Piitulainen JM, Kauko T, Aitasalo KM et al (2015) Outcomes of cranioplasty with synthetic materials and autologous bone grafts. World Neurosurg 83:708–714CrossRefPubMed
3.
Zurück zum Zitat Rish BL, Dillon JD, Meirowsky AM et al (1979) Cranioplasty: a review of 1030 cases of penetrating head injury. Neurosurgery 4:381–385CrossRefPubMed Rish BL, Dillon JD, Meirowsky AM et al (1979) Cranioplasty: a review of 1030 cases of penetrating head injury. Neurosurgery 4:381–385CrossRefPubMed
4.
Zurück zum Zitat Sanan A, Haines SJ (1979) Repairing holes in the head: a history of cranioplasty. Neurosurgery 40:588–603 Sanan A, Haines SJ (1979) Repairing holes in the head: a history of cranioplasty. Neurosurgery 40:588–603
5.
Zurück zum Zitat 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 71:938–950CrossRefPubMed 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 71:938–950CrossRefPubMed
6.
Zurück zum Zitat 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 43:1177–1183CrossRefPubMed 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 43:1177–1183CrossRefPubMed
7.
Zurück zum Zitat Feroze AH, Walmsley GG, Choudhri O et al (2015) Evolution of cranioplasty techniques in neurosurgery: historical review, pediatric considerations, and current trends. J Neurosurg 20:1–10CrossRef Feroze AH, Walmsley GG, Choudhri O et al (2015) Evolution of cranioplasty techniques in neurosurgery: historical review, pediatric considerations, and current trends. J Neurosurg 20:1–10CrossRef
8.
Zurück zum Zitat Serlo WS, Ylikontiola LP, Lähdesluoma N et al (2011) Posterior cranial vault distraction osteogenesis in craniosynostosis: estimated increases in intracranial volume. Childs Nerv Syst 27:627–633CrossRefPubMed Serlo WS, Ylikontiola LP, Lähdesluoma N et al (2011) Posterior cranial vault distraction osteogenesis in craniosynostosis: estimated increases in intracranial volume. Childs Nerv Syst 27:627–633CrossRefPubMed
9.
Zurück zum Zitat Wellisz T, Dougherty W, Gross J (1992) Craniofacial applications for the Medpor porous polyethylene flexblock implant. J Craniofac Surg 3:101–107CrossRefPubMed Wellisz T, Dougherty W, Gross J (1992) Craniofacial applications for the Medpor porous polyethylene flexblock implant. J Craniofac Surg 3:101–107CrossRefPubMed
10.
Zurück zum Zitat Moreira-Gonzalez A, Jackson IT, Miyawaki T et al (2003) Clinical outcome in cranioplasty: critical review in long-term follow-up. J Craniofac Surg 14:144–153CrossRefPubMed Moreira-Gonzalez A, Jackson IT, Miyawaki T et al (2003) Clinical outcome in cranioplasty: critical review in long-term follow-up. J Craniofac Surg 14:144–153CrossRefPubMed
11.
Zurück zum Zitat Vallittu PK (2014) High-aspect ratio fillers: fiber-reinforced composites and their anisotropic properties. Dent Mater 31:1–7CrossRefPubMed Vallittu PK (2014) High-aspect ratio fillers: fiber-reinforced composites and their anisotropic properties. Dent Mater 31:1–7CrossRefPubMed
12.
Zurück zum Zitat Thesleff T, Lehtimäki K, Niskakangas T et al (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68:1535–1540CrossRefPubMed Thesleff T, Lehtimäki K, Niskakangas T et al (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68:1535–1540CrossRefPubMed
13.
Zurück zum Zitat 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 157:275–280CrossRefPubMed 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 157:275–280CrossRefPubMed
14.
Zurück zum Zitat 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 156:805–811CrossRefPubMedPubMedCentral 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 156:805–811CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Velardi F, Amante PR, Caniglia M et al (2006) Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull. Childs Nerv Syst 22:1158–66CrossRefPubMed Velardi F, Amante PR, Caniglia M et al (2006) Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull. Childs Nerv Syst 22:1158–66CrossRefPubMed
16.
Zurück zum Zitat 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 38:201–209CrossRefPubMed 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 38:201–209CrossRefPubMed
17.
Zurück zum Zitat 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 3:530–540CrossRefPubMedPubMedCentral 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 3:530–540CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Berger M, Probst F, Schwartz C et al (2015) A concept for scaffold-based tissue engineering in alveolar cleft osteoplasty. J Cranio-Maxillofac Surg 43:830–836CrossRef Berger M, Probst F, Schwartz C et al (2015) A concept for scaffold-based tissue engineering in alveolar cleft osteoplasty. J Cranio-Maxillofac Surg 43:830–836CrossRef
19.
Zurück zum Zitat Leucht P, Helms JA (2015) Wnt signaling: an emerging target for bone regeneration. J Am Acad Orthop Surg 23:67–68CrossRefPubMed Leucht P, Helms JA (2015) Wnt signaling: an emerging target for bone regeneration. J Am Acad Orthop Surg 23:67–68CrossRefPubMed
20.
Zurück zum Zitat 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 101:144–149CrossRef 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 101:144–149CrossRef
21.
Zurück zum Zitat 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 105:417–422CrossRef 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 105:417–422CrossRef
22.
Zurück zum Zitat 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 31:581–7CrossRefPubMed 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 31:581–7CrossRefPubMed
23.
Zurück zum Zitat 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 25:144–158PubMed 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 25:144–158PubMed
24.
Zurück zum Zitat 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 107:157–163CrossRef 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 107:157–163CrossRef
25.
Zurück zum Zitat 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 109:60–67CrossRef 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 109:60–67CrossRef
26.
Zurück zum Zitat 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) 157:115–121CrossRef 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) 157:115–121CrossRef
27.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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) 39:233–242CrossRef 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) 39:233–242CrossRef
29.
Zurück zum Zitat 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 3:35–41PubMedPubMedCentral 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 3:35–41PubMedPubMedCentral
30.
Zurück zum Zitat 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 95:1537–1545CrossRefPubMed 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 95:1537–1545CrossRefPubMed
31.
Zurück zum Zitat Skovrlj B, Koehler SM, Anderson PA et al (2015) Association between BMP-2 and carcinogenicity. Spine (Phila Pa 1976) 40:1862–1871CrossRef Skovrlj B, Koehler SM, Anderson PA et al (2015) Association between BMP-2 and carcinogenicity. Spine (Phila Pa 1976) 40:1862–1871CrossRef
Metadaten
Titel
Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds
Publikationsdatum
19.01.2016
Erschienen in
Child's Nervous System / Ausgabe 4/2016
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-016-3017-2

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