MYC-Mediated Osseous Regeneration via BMSCs/PRP/β-TCP/PCL Bioprinted Constructs: Rapid Defect Rehabilitation and...

Bone defects present significant clinical challenges due to their morphological heterogeneity and structural complexity, necessitating regenerative strategies that integrate structural adaptability, biomechanical stability, and osteogenic potential. In this study, a bioengineered construct composed of bone marrow mesenchymal stem cells (BMSCs), platelet-rich plasma (PRP), polycaprolactone (PCL), and β-tricalcium phosphate (β-TCP) was fabricated using 3D bioprinting. In vitro assays assessed osteoprogenitor cell proliferation (CCK-8), migration (Transwell), differentiation (ALP staining), and endothelial tubulogenesis (Matrigel assay). In vivo bone regeneration was evaluated using a rabbit femoral condyle defect model, with histomorphometric analysis (Masson and COL-1 staining). Mechanistic insights were explored via RNA sequencing and western blot analysis. Clinical validation included pre- and postoperative assessments of visual analog scale (VAS) scores and computed tomography (CT) imaging in patients with osseous defects. The bioprinted constructs significantly enhanced BMSCs proliferation (p < 0.01), migration (p < 0.0001), and ALP activity (p < 0.0001), while promoting endothelial tubulogenesis (p < 0.01). In vivo, the BMSCs/PRP/PCL/β-TCP group exhibited greater Masson staining and collagen type I expression than controls at 2 weeks, 1 month, and 6 months postoperatively. Clinically, VAS scores significantly decreased (3.33 ± 1.63 pre-op vs. 0.50 ± 0.84 post-op, p = 0.005) with no severe complications. PRP concentration-dependently upregulated MYC expression (mRNA: p < 0.0001; protein: p < 0.0001), while MYC knockdown abrogated PRP-induced ALP and RUNX2 expression, confirming MYC's regulatory role in osteogenesis. In conclusion, BMSCs/PRP/PCL/β-TCP bioprinted constructs enhance MYC-mediated bone regeneration, demonstrating promising clinical potential for bone defect repair.