Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study

• Published in: International journal of molecular sciences 2024-05, Vol.25 (9), p.4604
• Main Authors: Haam, Dae-Won, Bae, Chun-Sik, Kim, Jong-Min, Hann, Sung-Yun, Yim, Chang-Min Richard, Moon, Hong-Seok, Oh, Daniel S
• Format: Article
• Language: English
• Subjects: Aluminum oxide; Animals; Bone Regeneration; Bone Substitutes; Bone Transplantation - methods; Bones; canine model; ceramic; CT imaging; Defects; Dogs; Durapatite; Growth factors; hydroxyapatite; Metabolism; Osteogenesis; Pilot Projects; Porosity; reconstruction; Regulatory approval; scaffold; Scintigraphy; segmental bone defect; Skin & tissue grafts; Surgery; Tibia - diagnostic imaging; Tissue Scaffolds - chemistry; Transplants & implants; X-Ray Microtomography
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094604

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.