Plenary Poster ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Preclinical evaluation of 3D printed Ca3Si-mPCL-CaP scaffolds for large tibial bone defects reconstruction in a sheep model (#302)

Flavia Medeiros Savi 1 2 3 , Siamak Saifzadeh 1 4 , Olivia Richardson 1 3 , Mahalakshmi Pandian 1 , Chengtie Wu 5 , Jiang Chang 5 , Chen Yang 5 , Cedryck Vaquette 6 7 , Dietmar W Hutmacher 1 3 8
  1. Centre in Regenerative Medicine, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, Australia
  2. ARC Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing, Brisbane, QLD, Australia
  3. Max Planck Queensland Center for the Materials Science of Extracellular Matrices, Queensland University of Technology, Brisbane, QLD, Australia
  4. Medical Engineering Research Facility, Queensland University of Technology, Kelvin Grove, Queensland, Australia
  5. State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China
  6. School of Dentistry, Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), The University of Queensland, Brisbane, QLD, Australia
  7. Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD, Australia
  8. ARC Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, Australia

Bone fractures, particularly tibial fractures, are a major public health concern, with non-union rates as high as 14%, leading to extended impairment and significant healthcare costs [1]. The current standard treatment for large bone defects is autologous bone grafting (ABG), which, despite its effectiveness, has limited availability and post-operative complications. Scaffold-guided bone tissue engineering (SGBTE) is a tissue engineering approach which leverages the use of 3D-printed scaffolds to guide bone tissue formation. 3D-printed scaffolds made of tricalcium silicate (Ca3Si) and medical grade polycaprolactone (mPCL) coated with calcium phosphate (CaP) have shown remarkable regenerative capabilities for treating large bone defects in preclinical models [2,3]. These scaffolds can be further combined with bone morphogenic protein 2 (BMP-2) to enhance bone formation. This study investigates the regenerative potential of 3D-printed Ca3Si-mPCL-CaP scaffolds using a 3cm tibial defect in a sheep model. Briefly, a 3cm defect was created in ten sheep tibiae and reconstructed using two experimental groups: I) Ca3Si with a mPCL-CaP mesh and II) Ca3Si + mPCL-CaP mesh + 1mg of BMP-2. The experimental groups were compared to the III) ABG and IV) mPCL scaffold control groups. After 12-months bone formation and mechanical properties were evaluated through x-rays, biomechanical testing, Micro-CT, and various microscopic and histological analyses. Results showed complete bridging of the defect after 12 months in both experimental groups, with the group receiving BMP-2 demonstrating superior mechanical properties and higher bone volumes compared to the ABG and mPCL scaffold groups. Key findings included a well-aligned collagen deposition around the Ca3Si scaffold and mPCL-CaP mesh scaffold, supporting cortical and lamellar bone formation, osteocytes in direct contact with scaffolds, along with secondary osteon formation. This study validates the potential of 3D printed Ca3Si + mPCL-CaP scaffolds as a viable alternative to the limited ABG, laying the groundwork for future clinical applications.

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  2. [2] Yang, C.; Wang, X.; Ma, B.; Zhu, H.; Huan, Z.; Ma, N.; Wu, C.; Chang, J. 3D-Printed Bioactive Ca 3 SiO 5 Bone Cement Sca Ff Olds with Nano Surface Structure for Bone Regeneration. ACS Appl. Mater. Interfaces 2017, 9, 1944–8244, doi:10.1021/acsami.6b14297.
  3. [3] Sparks, D.S.; Savi, F.M.; Dlaska, C.E.; Saifzadeh, S.; Brierly, G.; Ren, E.; Cipitria, A.; Reichert, J.C.; Wille, M.-L.; Schuetz, M.A.; et al. Convergence of Scaffold-Guided Bone Regeneration Principles and Microvascular Tissue Transfer Surgery. Sci. Adv. 2023, 9, eadd6071, doi:10.1126/sciadv.add6071.