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Intraoperative Bioprinting for Craniomaxillofacial Bone Reconstruction in Rats and Sheep
Miji Yeo1,2, Deepak Gupta1,2, Irem Deniz Derman1,2
1Engineering Science and Mechanics Pennsylvania State University University Park PA 16802 USA.
Small Science
|November 19, 2025
Summary
Intraoperative bioprinting (IOB) reconstructs cranial bone defects using a collagen bioink with stem cells or BMP-2. This automated surgical technique shows significant bone regeneration and mechanical enhancement in rat and sheep models.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Surgical Innovation
Background:
- Craniomaxillofacial reconstruction is complex, requiring extensive manual surgery that escalates with defect size.
- Existing methods face challenges in achieving optimal bone regeneration and structural integrity.
Purpose of the Study:
- To develop and evaluate intraoperative bioprinting (IOB) for cranial bone defect reconstruction.
- To assess the efficacy of a novel collagen-based bioink with human adipose-derived stem cells (hADSCs) or bone morphogenetic protein-2 (BMP-2).
Main Methods:
- Formulation of a collagen-based bioink with optimized collagen concentration and hADSC dispersion.
- Application of IOB using a 3-axis bioprinter in a rat calvarial defect model (39.3 mm³).
- IOB application using a 6-axis robotic arm in a larger sheep calvarial defect model (1,209 mm³).
Main Results:
- In rats, IOB achieved ≈90% bone coverage within 8 weeks.
- In sheep, IOB demonstrated ≈80% bone coverage by Week 12.
- Sheep defects treated with IOB showed significant mechanical improvements (Young's modulus, peak force, energy) compared to controls.
Conclusions:
- IOB is a viable automated surgical approach for cranial bone reconstruction.
- The developed bioink formulation supports cytocompatibility, bioprintability, and osteogenic activity.
- Successful translation to both small and large animal models highlights IOB's clinical potential.

