Bone regeneration in critical-sized mandibular symphysis defects using bioceramics with or without bone marrow mesenchymal stem cells in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats

Dent Mater. 2022 Aug;38(8):1283-1300. doi: 10.1016/j.dental.2022.06.019. Epub 2022 Jun 16.

Abstract

Objectives: To compare new bone formation in mandibular critical-sized bone defects (CSBDs) in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats filled with bioceramics (BCs) with or without bone marrow mesenchymal stem cells (BMSCs).

Methods: A total of 64 adult female Sprague-Dawley rats were randomized into four groups (n = 16 per group): Group 1 healthy, Group 2 diabetic, Group 3 osteoporotic, and Group 4 diabetic-osteoporotic rats. Streptozotocin was used to induce type 1 diabetes in Group 2 and 4, while bilateral ovariectomy was used to induce osteoporosis in Group 3 and 4. The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BC (hydroxypatatite 60% and β-tricalcium phosphate 40%) alone and eight with BMSCs cultured on BC. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2).

Results: In all groups (healthy, diabetics, osteoporotics, and diabetics-osteoporotics), the CSBDs filled with BC + BMSCs showed greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with CSBDs treated with BC alone (at 4 and 8 weeks).

Conclusions: Application of BMSCs cultured on BCs improves bone regeneration in CSBDs compared with application of BCs alone in healthy, diabetic, osteoporotic, and diabetic-osteoporotic rats.

Keywords: Bioceramics; Bone marrow mesenchymal stem cells; Diabetes; Mandibular symphysis; Osteoporosis.

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Regeneration
  • Diabetes Mellitus* / metabolism
  • Diabetes Mellitus* / pathology
  • Female
  • Mandible / metabolism
  • Mandible / pathology
  • Mesenchymal Stem Cells*
  • Osteogenesis
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / metabolism
  • X-Ray Microtomography

Substances

  • Vascular Endothelial Growth Factor A