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
Sajad Daneshi S. Tayebi L. Talaei-Khozani T. Tavanafar S. Hadaegh A.H. Rasoulianboroujeni M. Rastegari B. Asadi-Yousefabad S.-L. Nammian P. Zare S. Mussin N.M. Kaliyev A.A. Zhelisbayeva K.R. Tanideh N. Tamadon A.
13 May 2024American Chemical Society
ACS Biomaterials Science and Engineering
2024#10Issue 53316 - 3330 pp.
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.
mandibular defects , mesenchymal stem cells , osteogenesis , scaffold design , tissue engineering
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Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
Marquette University School of Dentistry, Milwaukee, 53233, WI, United States
Tissue Engineering Laboratory, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
Department of Oral and Maxillofacial Surgery, School of Dentistry, Birjand University of Medical Sciences, Birjand, 97178, Iran
Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
Ryangene Biolab Co. Ltd, Shiraz, 71348, Iran
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
Department of Surgery No. 2, West Kazakhstan Medical University, Aktobe, 030012, Kazakhstan
Department of Scientific Works, West Kazakhstan Marat Ospanov Medical University, Aktobe, 030012, Kazakhstan
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 71348, Iran
PerciaVista R&D Co., Shiraz, 71348, Iran
Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, 030012, Kazakhstan
Stem Cells Technology Research Center
Marquette University School of Dentistry
Tissue Engineering Laboratory
Department of Oral and Maxillofacial Surgery
Department of Parasitology and Mycology
Ryangene Biolab Co. Ltd
Diagnostic Laboratory Sciences and Technology Research Center
Department of Molecular Medicine
Department of Surgery No. 2
Department of Scientific Works
Department of Pharmacology
PerciaVista R&D Co.
Department of Natural Sciences
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