Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel–Ceramic Scaffold Application

Apr 15, 2024ACS biomaterials science & engineering

Using 3D-Printed Scaffolds with Cells to Improve Blood Vessel Growth and Bone Healing in Large Jaw Bone Defects in Rabbits

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

Significant increases in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization were observed with the use of a collagen-coated 3D-printed scaffold loaded with stem cells.

The engineered scaffold demonstrated enhanced bone regeneration in a rabbit model with critical-sized mandibular defects.
Histomorphometric analysis indicated a substantial improvement in bone formation compared to control groups.
RT-PCR results showed significant upregulation of genes associated with bone formation.
Collagen coating and the presence of stem cells played critical roles in the observed regeneration process.
A decrease in fibroblasts/fibrocytes and connective tissue was noted in the experimental group.

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In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (β-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/β-TCP scaffold, a stem cell-loaded 3D-printed nHA/β-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/β-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/β-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/β-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

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Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel–Ceramic Scaffold Application

Abstract

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