BMP2-releasing 3D-Printed Scaffold for Alveolar Bone Tissue Engineering

Objectives: We have recently reported a 3D-printed scaffold embedding control-delivery vehicle of growth factors for craniofacial tissue engineering. The present study was designed to determine an optimal internal microstructure and dose of growth factor-delivering vehicles in the 3D-printed scaffolds for alveolar bone tissue engineering with stem/progenitor cells.
Methods: Polycaprolactone (PCL)-hydroxyapatite (HA) scaffolds (5 x 5 mm²) were fabricated using a 3D-Bioplotter^TM. PCL-HA (90:10 wt%) was dispensed through a micro-needle to create interlaid strands (400 - 700 μm) and microchannels (300 - 500 μm). For a control-delivery, PLGA microspheres (µS)-encapsulating BMP2 (5 µg) were embedded in the microstrands at different doses (50 and 100 mg/g PCL). Upon measuring in vitro BMP2 release, compressive moduli and yield strength were measured at a constant strain rate (.02%/min) to determine the effects of µS-embedding on the mechanical stability of scaffold. Alvelolar bone stem cells (ABSCs) from human patients following approved IRB protocol were delivered into the microchannels of the scaffolds. After 4 wks in osteogenic medium, the ABSC-seeded scaffolds were harvested and analyzed.
Results: BMP2 showed a sustained release from scaffolds up to 42 days. Embedded-PLGA µS in 3D-printed PCL scaffolds resulted in compressive moduli at 43 – 84% of PCL alone scaffolds (p<0.05). Interestingly, the low µS dose (50 mg/g PCL) yielded significantly lower compressive modulus than high µS (100 mg/g PCL) with 400 and 550 μm microstrands. In contrast, the high µS dose showed significantly lower compressive modulus than the low µS dose with 700 μm microstrands. No change was observed in yield modulus.
Conclusions: Mineral deposition and AB-related gene expressions are expected to be affected by the microstructure of the scaffolds with BMP2-µS. Our findings demonstrating the effect of design parameters on 3D-printed scaffolds may have implication in alveolar bone tissue engineering to replace craniofacial bone defects.