Low-Temperature Three-Dimensional Bioprinted Dual-Factor rhBMP-2/VEGF-165 Biomimetic Scaffolds for Synergistic
Jiahao Zeng1,2, Yefan Zhang1, Menglong Wang1
1Department of Orthopedics, The First Affiliated Hospital (Xijing Hospital), Air Force Medical University, Xi'an 710032, China.
ACS Biomaterials Science & Engineering
|October 31, 2025
Summary
This study developed a 3D-printed bone scaffold using polycaprolactone and bone powder, loaded with growth factors to enhance bone repair. The dual-growth factor scaffold significantly improved bone regeneration and vascularization in rabbit models.
Area of Science:
- Biomaterials Science
- Orthopedic Surgery
- Regenerative Medicine
Background:
- Large segmental bone defects pose significant challenges in orthopedic surgery.
- Three-dimensional (3D) printing and growth factor-loaded scaffolds offer promising solutions for bone defect repair.
- Developing ideal scaffolds with comprehensive clinical requirements remains an ongoing effort.
Purpose of the Study:
- To design and evaluate a biomimetic, bioactive bone repair scaffold using low-temperature 3D bioprinting.
- To assess the osteogenic and angiogenic capacity of scaffolds with varying growth factor combinations (rhBMP-2 and VEGF-165) in a rabbit radial bone defect model.
Main Methods:
- Fabrication of four composite scaffolds: PCL/XBP (PB), PCL/XBP with rhBMP-2 (PBB), PCL/XBP with VEGF-165 (PBV), and PCL/XBP with both (PBBV).
- Characterization of scaffold porosity and mechanical properties.
- In vitro biocompatibility and osteogenic/angiogenic potential assessment using BMSCs and mouse muscle pouch implantation.
- In vivo evaluation in large segmental rabbit radial defects using micro-CT, histomorphometry, and angiography.
Main Results:
- Scaffolds exhibited interconnected porous structures (58.7% porosity) and appropriate mechanical strength.
- Controlled release profiles demonstrated sustained BMP-2 and biphasic VEGF-165 release.
- In vitro and in vivo studies confirmed excellent biocompatibility and early osteogenic-angiogenic potential.
- The PBBV scaffold group showed significantly superior osteogenic and angiogenic performance compared to other groups in rabbit radial defects.
Conclusions:
- The dual-growth factor (BMP-2/VEGF-165) loaded biomimetic scaffold effectively promotes bone regeneration and vascularization.
- This 3D-printed scaffold system addresses limitations in large segmental bone defect repair by combining structural support, bioactivity, and controlled release.
- The developed scaffold represents a translatable solution for enhancing bone defect reconstruction through synergistic vascularization and osteogenesis.


