Functionally-graded Scaffold (FGS) and Bone Marrow-derived Mononuclear Cells (BMMC) for the Treatment of Early Steroid-induced Osteonecrosis of the Femoral Head in Rabbits

Stuart Goodman 1 Masahiro Maruyama 2 Akira Nabeshima 5 Chi-Chun Pan 1 Anthony Behn 1 Timothy Thio 1 Tzuhua Lin 1 Jukka Pajarinen 4 Toshiyuki Kawai 3 Michiaki Takagi 2 Yunzhi Yang 1
1Orthopaedic Surgery, Stanford University, USA
2Orthopaedic Surgery, Yamagata University, Japan
3Orthopaedic Surgery, Kyoto University, Japan
4Orthopaedic Surgery, Helsinki University, Finland
5Orthopaedic Surgery, Kyushu University, Japan

Introduction: This study investigates the efficacy of a customized load-bearing, bioactive, functionally-graded scaffold (FGS) ± BMMC using a rabbit-steroid induced model of ONFH.

Methods: The 3D printed cylindrical FGS was made of polycaprolactone and β-TCP and had low porosity segments (15% proximal and distal segments) and a high porosity (60%) middle segment.

Twenty-two mature male NZW rabbits received methylprednisolone acetate (20mg/kg) IM 4 weeks pre-operatively. Four groups included: core alone, core+BMMC, FGS alone, FGS+BMMC. The core decompression was 2.4 mm in diameter. In the core+BMMC group, BMMCs were injected into the core. In the FGS group, FGS was inserted into a bone tunnel. In the FGS+BMMC group, BMMCs were injected before implanting the FGS. Eight weeks post-operatively, the core area was harvested. MicroCT analysis was performed and a cylindrical region of interest (ROI) was defined.

Results: Bone ingrowth ratio in the proximal segment was 92.3%±6.2% in the FGS group, which was significantly higher than 69.5%±18.3% in the CD group (p < 0.01) and 54.0%±22.2% in the BMMC group (p < 0.005). Bone ingrowth ratio in the proximal segment was 96.3%±1.7% in the FGS+BMMC group, which was significantly higher than in the BMMC group (p < 0.005). The percentage of empty lacunae in the trabecular bone was 53.4%±13.8% in the CD group, 39.6%±7.5% in the FGS group, 21.4%±1.4% in the BMMC group and 19.9%±14.2% in the FGS+BMMC group. The percentage of the empty lacunae in the CD group was significantly higher than in the BMMC and the FGS+BMMC groups.

Discussion: The FGS increased new bone formation after CD using this in vivo model. BMMCs injected into the CD decreased the osteonecrotic area. The combination of FGS and BMMC together may improve the outcome of CD for early stage ONFH by providing both biological and biomechanical cues for bone tissue regeneration.









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