V Hivernaud1, F Grimaud2, J Guicheux3, S Portron4, R Pace4, P Pilet3, S Sourice4, S Wuillem5, H Bertin6, R Roche7, F Espitalier3, P Weiss3, P Corre2. 1. Inserm, UMR-S 1229, R-MeS Lab, Nantes, 44042, France; Université de Nantes, UMR-S 1229 R-MeS Lab, UFR odontologie, Nantes, 44042, France; STEMCIS, Besançon, France. Electronic address: vincent.hivernaud@hotmail.fr. 2. Inserm, UMR-S 1229, R-MeS Lab, Nantes, 44042, France; Université de Nantes, UMR-S 1229 R-MeS Lab, UFR odontologie, Nantes, 44042, France; CHU de Nantes, PHU 4 OTONN, Nantes, 44042, France; CHU de Nantes, clinique de stomatologie et chirurgie maxillo-faciale, Nantes, 44042, France. 3. Inserm, UMR-S 1229, R-MeS Lab, Nantes, 44042, France; Université de Nantes, UMR-S 1229 R-MeS Lab, UFR odontologie, Nantes, 44042, France; CHU de Nantes, PHU 4 OTONN, Nantes, 44042, France. 4. Inserm, UMR-S 1229, R-MeS Lab, Nantes, 44042, France; Université de Nantes, UMR-S 1229 R-MeS Lab, UFR odontologie, Nantes, 44042, France. 5. CHU de Nantes, laboratoire d'hématologie, Nantes, 44042, France. 6. CHU de Nantes, clinique de stomatologie et chirurgie maxillo-faciale, Nantes, 44042, France. 7. STEMCIS, Besançon, France.
Abstract
BACKGROUND: In craniofacial reconstruction, the gold standard procedure for bone regeneration is the autologous bone graft (BG). However, this procedure requiring bone harvesting is a source of morbidity. Bone substitutes, such as biphasic calcium phosphate (BCP), represent an interesting alternative but are not sufficient for bone healing in hypoplastic conditions. In such conditions, osteoprogenitors are essential to provide osteoinduction. Previous studies have shown that BCP associated with total bone marrow (TBM) provides same bone reconstruction as bone graft in a rat model of calvaria defect. Furthermore, adipose tissue stromal vascular fraction (SVF) seems to be another promising source of osteoprogenitor cells that can be used intra-operatively. This study aimed to combine, intra-operative BCP-based bone tissue engineering strategies with TBM or SVF from human sources. METHODS: 5 mm critical-size calvaria defects were performed in 18 nude rat. The defects were filled with intra-operative bone tissue engineering procedures: human BG, human TBM + BCP, human SVF + BCP and, rat TBM + BCP. Animals were sacrificed 8 weeks after implantation and calvaria were processed for histological and radiological examinations. Implanted cells were labelled with a fluorochrome. RESULTS: Micro-CT analysis revealed partial repair of bone defect. Only hBG significantly succeeded in healing the defect (43.1%). However, low rate of newly formed bone tissue was observed in all tissue engineering conditions (hTBM, hSVF, ratTBM). DISCUSSION: The lack of bone formation observed in this study could possibly be attributed to the model. CONCLUSION: This study combined with a literature analysis show the stringency of the nude rat calvaria model in term of bone regeneration.
BACKGROUND: In craniofacial reconstruction, the gold standard procedure for bone regeneration is the autologous bone graft (BG). However, this procedure requiring bone harvesting is a source of morbidity. Bone substitutes, such as biphasic calcium phosphate (BCP), represent an interesting alternative but are not sufficient for bone healing in hypoplastic conditions. In such conditions, osteoprogenitors are essential to provide osteoinduction. Previous studies have shown that BCP associated with total bone marrow (TBM) provides same bone reconstruction as bone graft in a rat model of calvaria defect. Furthermore, adipose tissue stromal vascular fraction (SVF) seems to be another promising source of osteoprogenitor cells that can be used intra-operatively. This study aimed to combine, intra-operative BCP-based bone tissue engineering strategies with TBM or SVF from human sources. METHODS: 5 mm critical-size calvaria defects were performed in 18 nude rat. The defects were filled with intra-operative bone tissue engineering procedures: human BG, humanTBM + BCP, human SVF + BCP and, ratTBM + BCP. Animals were sacrificed 8 weeks after implantation and calvaria were processed for histological and radiological examinations. Implanted cells were labelled with a fluorochrome. RESULTS: Micro-CT analysis revealed partial repair of bone defect. Only hBG significantly succeeded in healing the defect (43.1%). However, low rate of newly formed bone tissue was observed in all tissue engineering conditions (hTBM, hSVF, ratTBM). DISCUSSION: The lack of bone formation observed in this study could possibly be attributed to the model. CONCLUSION: This study combined with a literature analysis show the stringency of the nude rat calvaria model in term of bone regeneration.
Authors: Florian Andreas Probst; Riham Fliefel; Egon Burian; Monika Probst; Matthias Eddicks; Matthias Cornelsen; Christina Riedl; Hermann Seitz; Attila Aszódi; Matthias Schieker; Sven Otto Journal: Sci Rep Date: 2020-02-06 Impact factor: 4.379