Abstract
OBJECTIVE: This study aims to evaluate the efficacy of biphasic mineralized collagen/polycaprolactone (bMC/PCL) scaffolds in repairing large load-bearing bone defects, particularly femoral defects, using a sheep model. METHODS: The bMC/PCL scaffolds were prepared by combining porous mineralized collagen/polycaprolactone (pMC/PCL) with compact mineralized collagen/polycaprolactone (cMC/PCL). The scaffolds were characterized using scanning electron microscopy to observe the microstructure and compression testing to assess mechanical properties. Twenty female sheep were selected to create a 20 mm femoral defect model, divided into a blank group (no material implanted) and an experimental group (bMC/PCL scaffolds implanted), with 10 sheep in each group. Bone healing and lower limb functional recovery were assessed at 1 month, 3 months, and 6 months postoperatively using Lane-Sandhu scores and visual analog scale scores for lameness. Additionally, bone repair progress was analyzed through X-ray, Micro-CT, and histological analyses. RESULTS: Compared with the blank group, the bMC/PCL scaffold group showed significant improvement in bone defect repair. At 3 and 6 months postoperatively, X-ray, Micro-CT scans, and histological staining indicated stable scaffold integration and gradual new bone formation. The Lane-Sandhu scores in the experimental group were 3.60 ± 0.548 and 4.00 ± 0.707 at 3 and 6 months, respectively, whereas the blank group experienced plate/screw breakage leading to fixation failure, with scores of 1, indicating better bone healing in the experimental group. The lameness scores in the experimental group were 2.71 ± 0.97 and 1.48 ± 0.86 at 3 and 6 months, respectively, significantly lower than those in the blank group (p < 0.0001 and p = 0.0002). Micro-CT analysis showed that bone volume to tissue volume ratio increased from 28.07 ± 9.22 % to 62.02 ± 11.82 %, bone mineral density increased from 0.392 ± 0.032 g/cm(3) to 0.583 ± 0.125 g/cm(3), trabecular thickness increased from 0.690 ± 0.224 mm to 1.049 ± 0.089 mm, and trabecular separation decreased from 2.766 ± 1.183 mm to 0.501 ± 0.268 mm at 3 and 6 months postoperatively. CONCLUSION: This study evaluated the efficacy of bMC/PCL scaffolds in repairing large load-bearing bone defects. The bMC/PCL scaffolds demonstrated good bioactivity and mechanical properties, indicating promising clinical application prospects. Future studies should further verify the safety and efficacy of these scaffolds in a wider range of animal models to support their clinical application. SIGNIFICANCE STATEMENT: The bMC/PCL scaffolds offer a promising solution for large femoral bone defects, with potential for clinical use in orthopedic and trauma surgeries. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The application of bMC/PCL scaffolds in clinical practice is expected to significantly advance the treatment of large bone defects, particularly weight-bearing bone defects. The study shows that bMC/PCL scaffolds have a significant impact on the repair of large weight-bearing bone defects and functional recovery, indicating their potential for application in orthopedics and trauma care. Specifically, the material's supportive role in weight-bearing bones offers new possibilities for its use in the repair of weight-bearing bone defects. Furthermore, the performance of bMC/PCL scaffolds in bone healing makes them an ideal candidate material for treating various bone defects, with broad clinical application prospects. Further clinical trials are necessary to confirm their safety and efficacy in human patients.