Bone Growth Capacity of Human Umbilical Cord Mesenchymal Stem Cells and BMP-2 Seeded Into Hydroxyapatite/Chitosan/Gelatin Scaffold in Alveolar Cleft Defects: An Experimental Study in Goat

Cleft Palate Craniofac J. 2021 Jun;58(6):707-717. doi: 10.1177/1055665620962360. Epub 2020 Oct 14.

Abstract

Objective: To evaluate bone regeneration in alveolar defects treated with human umbilical cord-derived mesenchymal stem cells (hUCMSCs), hydroxyapatite/chitosan/gelatin (HA/CS/Gel) scaffold, and bone morphogenic protein-2 (BMP-2) in Capra hircus models.

Design: Randomized posttest-only control group design.

Setting: Animal Hospital at Bogor Agricultural Institute.

Participants: Healthy and equally treated 24 female Capra hircus/goats.

Intervention: Animals were randomly assigned to 3 experimental group design (iliac crest alveolar bone graft/ICABG [control], HA/Cs/Gel+BMP-2 [Novosys], and HA/Cs/Gel+BMP-2+UCMSCs). Graft materials were implanted in surgically made alveolar defects.

Main outcome measures: Postoperative functional score and operating time were assessed. New bone growth, bone density, inflammatory cells recruitment, and neoangiogenesis were evaluated based on radiological and histological approach at 2 time points, week 4 and 12. Statistical analysis was done between treatment groups.

Results: Operating time was 34% faster and functional score 94.5% more superior in HA/Cs/Gel+BMP-2+hUCMSC group. Bone growth capacity in HA/Cs/Gel+BMP-2+UCMSCs mimicked ICABG, but ICABG showed possibility of bone loss between week 4 and 12. The HA/Cs/Gel+BMP-2+UCMSCs showed early bone repopulation and unseen inflammatory cells and angiogenesis on week 12.

Discussion and conclusion: The HA/Cs/Gel+BMP-2+hUCMSCs were superior in enhancing new bone growth without donor site morbidity compared to ICABG. The presence of hUCMSCs in tissue-engineered alveolar bone graft (ABG), supported with paracrine activity of the resident stem cells, initiated earlier new bone repopulation, and completed faster bone regeneration. The HA/Cs/Gel scaffold seeded with UCMSCs+BMP-2 is a safe substitute of ICABG to close alveolar bone defects suitable for patients with cleft lip, alveolus, and palate.

Keywords: alveolar bone grafts; bone regeneration; hydroxyapatite/chitosan/gelatin scaffold; iliac crest bone graft; mesenchymal stem cells; tissue engineering.

MeSH terms

  • Animals
  • Bone Development
  • Bone Regeneration
  • Chitosan*
  • Durapatite
  • Female
  • Gelatin
  • Goats
  • Humans
  • Mesenchymal Stem Cells*
  • Tissue Scaffolds
  • Umbilical Cord

Substances

  • Gelatin
  • Chitosan
  • Durapatite