PCL–GelMA Hybrid Bioprinting: Engineering High-Stiffness 3D Tissue Models with the BIO X
Introduction: Challenges in Tissue Engineering and the Hybrid Approach
Designing scaffolds that provide both high mechanical strength and a biologically supportive environment for cell attachment remains a central challenge in tissue engineering.
Single-material scaffolds often force a trade-off—mechanically strong materials tend to be less cytocompatible, while biologically favorable materials often lack structural integrity.
The BIO X platform from CELLINK overcomes this limitation through hybrid bioprinting, combining PCL (poly(ε-caprolactone)), a thermoplastic polymer with high stiffness, and GelMA (gelatin methacryloyl), a photocrosslinkable hydrogel with excellent biocompatibility.
This approach enables the fabrication of 3D tissue models that simultaneously achieve structural stability and a cell-friendly microenvironment.
Technical Highlights
1. Hybrid Structures Combining PCL Frames and GelMA Hydrogels
The workflow below illustrates the complete hybrid printing process using the BIO X, including PCL extrusion, GelMA dispensing, photocrosslinking, culture, and evaluation.

Using both the Thermoplastic Printhead (TPPH) and the Temperature-controlled Printhead (TCPH),
the BIO X can precisely print PCL lattice structures and simultaneously deposit cell-laden GelMA within the voids, forming a fully integrated hybrid scaffold.
2. PCL Lattice Structures with Tunable Void Sizes

By adjusting the spacing of the PCL lattice, the overall mechanical properties—particularly stiffness—can be tuned to match the requirements of specific tissue types.
3. Compressive Modulus: Mechanical Performance of the Hybrid Scaffold

The 1.0 mm lattice produced a modulus of approximately 3.2 MPa, while the 0.5 mm lattice achieved about 4.9 MPa.
These values correspond closely to the stiffness of native soft tissues such as nasal and articular cartilage, demonstrating the ability to tune mechanics through lattice design alone.
4. MSC Proliferation Within the Hybrid Scaffold

Over 14 days of culture, cell numbers increased substantially—approximately 4.5-fold in the 1.0 mm lattice and 6.1-fold in the 0.5 mm lattice—indicating a supportive environment for long-term cell growth.
5. Cell Viability and Morphology: Live/Dead Fluorescent Imaging

Viable MSCs (green) were uniformly distributed throughout the GelMA and along the PCL frame. Cells exhibited increasing spreading over time, confirming the cytocompatibility of the hybrid fabrication process.
6. MSC Viability (Day 7 / Day 14)

Both Day 7 and Day 14 demonstrated consistently high viability of approximately 90%, confirming that photocrosslinking and the overall fabrication workflow remain highly cell-friendly.
Applications: Cartilage, Neural Models, and Beyond
The hybrid approach provides tunable mechanical performance, biological compatibility, and structural flexibility,
enabling applications in cartilage tissue models, nerve guide conduits, connective tissue engineering, and other advanced 3D biological constructs.
Conclusion
PCL–GelMA hybrid bioprinting with the BIO X enables the creation of next-generation 3D tissue models that combine high structural stiffness with excellent cytocompatibility.
This technology shows strong promise for future applications in regenerative medicine, tissue engineering, and biofabrication research.
Explore additional CELLINK Application Notes:
https://www.cellink.com/application-notes/?cat_filter=c_all&product_filter=p_all


