Effectiveness of biomechanically stable pergola-like additively manufactured scaffold for extraskeletal vertical bone augmentation

Wei Yang; Chao Wang; Wenping Luo; Antonio Apicella; Ping Ji; Gong Wang; Bingshan Liu; Yubo Fan

doi:10.3389/fbioe.2023.1112335

Effectiveness of biomechanically stable pergola-like additively manufactured scaffold for extraskeletal vertical bone augmentation

Front Bioeng Biotechnol. 2023 Mar 28:11:1112335. doi: 10.3389/fbioe.2023.1112335. eCollection 2023.

Authors

Wei Yang¹, Chao Wang^{1

2}, Wenping Luo³, Antonio Apicella⁴, Ping Ji¹, Gong Wang⁵, Bingshan Liu⁵, Yubo Fan²

Affiliations

¹ Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
² Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, School of Engineering Medicine, Beihang University, Beijing, China.
³ Laboratory Animal Center, Southwest University, Chongqing, China.
⁴ Advanced Materials Lab, Department of Architecture and Industrial Design, University of Campania, Aversa, Italy.
⁵ Technology and Engineering Center for Space Utilization, Chinese Academy of Sciences, Beijing, China.

Abstract

Objective: Extraskeletal vertical bone augmentation in oral implant surgery requires extraosseous regeneration beyond the anatomical contour of the alveolar bone. It is necessary to find a better technical/clinical solution to solve the dilemma of vertical bone augmentation. 3D-printed scaffolds are all oriented to general bone defect repair, but special bone augmentation design still needs improvement. Methods: This study aimed to develop a structural pergola-like scaffold to be loaded with stem cells from the apical papilla (SCAPs), bone morphogenetic protein 9 (BMP9) and vascular endothelial growth factor (VEGF) to verify its bone augmentation ability even under insufficient blood flow supply. Scaffold biomechanical and fluid flow optimization design by finite element analysis (FEA) and computational fluid dynamics (CFD) was performed on pergola-like additive-manufactured scaffolds with various porosity and pore size distributions. The scaffold geometrical configuration showing better biomechanical and fluid dynamics properties was chosen to co-culture for 2 months in subcutaneously into nude mice, with different SCAPs, BMP9, and (or) VEGF combinations. Finally, the samples were removed for Micro-CT and histological analysis. Results: Micro-CT and histological analysis of the explanted scaffolds showed new bone formation in the "Scaffold + SCAPs + BMP9" and the "Scaffold + SCAPs + BMP9 + VEGF" groups where the VEGF addition did not significantly improve osteogenesis. No new bone formation was observed either for the "Blank Scaffold" and the "Scaffold + SCAPs + GFP" group. The results of this study indicate that BMP9 can effectively promote the osteogenic differentiation of SCAPs. Conclusion: The pergola-like scaffold can be used as an effective carrier and support device for new bone regeneration and mineralization in bone tissue engineering, and can play a crucial role in obtaining considerable vertical bone augmentation even under poor blood supply.

Keywords: additively manufactured (3D-printed); adverse microenvironment; bone morphogenetic protein 9 (BMP9); bone tissue engineering; extraskeletal bone; finite element analysis; stem cells from the apical papilla (SCAPs); vertical bone augmentation.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No.12072055, 11872135, 12172034, U20A20390, and 32070539), Natural Science Foundation of Beijing (Grant No. L212063), the Fundamental Research Funds for the Central Universities and the 111 Project (No. B13003).