How Fish Gelatin and Plant Cellulose are Revolutionizing 3D Bioprinting
Imagine a future where instead of waiting for organ donors, doctors can simply print new tissues customized to a patient's needs. This isn't science fiction—it's the promise of 3D bioprinting, an emerging technology that aims to create functional human tissues layer by layer.
At the heart of this revolutionary technology are bioinks, special materials that can safely encapsulate living cells while being precisely deposited by 3D printers. Yet creating the perfect bioink—one that's both biologically compatible and mechanically robust—has remained a significant challenge. Enter an unexpected duo: fish gelatin and microcrystalline cellulose. Recent research reveals how these natural materials from the ocean and plants might hold the key to advancing tissue engineering, turning what was once waste into the building blocks of medical innovation.
Layer-by-layer deposition of living cells and biomaterials to create tissue constructs.
Materials that encapsulate cells and provide structural support during and after printing.
Gelatin, a substance most of us associate with food products, has long been valued in medicine for its biocompatibility and ability to support cell growth. Traditionally derived from mammalian sources like pigs and cows, gelatin comes with baggage—concerns about prion diseases and religious restrictions limit its universal application 1 2 .
Fish gelatin (FG) emerges as a brilliant solution. Sourced from fish processing byproducts like skin, bones, and fins that would otherwise go to waste, FG adds value to seafood industry waste while avoiding the pitfalls of mammalian gelatin 1 4 .
While fish gelatin provides an excellent biological environment for cells, it lacks mechanical strength. This is where microcrystalline cellulose (MCC) enters the picture. Derived from plant cell walls, MCC is a renewable biomaterial consisting of tiny crystalline cellulose particles 1 2 .
MCC brings several advantages to the bioink formulation:
Synergy: When combined, these two materials create a symbiotic relationship—the fish gelatin provides the biological cues that cells need, while the MCC adds the structural integrity necessary for 3D printing.
Extrusion-based bioprinting, one of the most common and affordable bioprinting techniques, works by pushing bioink through a printhead in the form of fine filaments that are deposited layer by layer to build three-dimensional structures 1 2 .
The bioink must be viscous enough to hold its shape after printing but fluid enough to exit the printhead smoothly. It needs to support the weight of subsequent layers without collapsing and maintain precise patterning while being gentle on living cells.
Bioinks must balance viscosity, printability, and cell compatibility.
In a groundbreaking 2025 study, researchers systematically developed and tested FG/MCC biomaterial inks 1 2 . The process began with creating composite hydrogels by carefully blending fish gelatin with varying concentrations of microcrystalline cellulose.
Composite hydrogels created by blending fish gelatin with varying MCC concentrations.
Mixtures loaded into extrusion-based bioprinter to fabricate detailed scaffold structures.
Multiple advanced techniques used to evaluate the created bioinks and scaffolds.
| Reagent/Material | Function/Role | Key Characteristics |
|---|---|---|
| Fish Gelatin (FG) | Base polymer matrix | Biocompatible, biodegradable, contains cell-adhesive motifs, thermoresponsive |
| Microcrystalline Cellulose (MCC) | Reinforcing agent | High mechanical strength, renewable, biodegradable, forms hydrogen bonds with FG |
| Genipin | Crosslinking agent | Natural crosslinker from Gardenia fruits, low cytotoxicity compared to synthetic alternatives |
| Glycerol | Plasticizer | Improves flexibility and processability of polymer matrix |
| LAP Photoinitiator | Enables photopolymerization | Allows light-based crosslinking of methacrylated gelatin derivatives |
One of the most critical findings from the research was how MCC content dramatically influenced the printing temperature window—the range of temperatures at which the bioink could be successfully printed. Gelatin-based inks are notoriously temperature-sensitive, and finding the right printing conditions is essential for success 1 2 .
The researchers discovered that as MCC content increased, the optimal printing temperature also increased. They used a clever quantitative method to evaluate printability based on the geometry of pores in the printed structures, with ideal bioinks achieving values between 0.9 and 1.1 1 2 .
Perhaps the most important rheological property the team identified was shear-thinning behavior. This phenomenon refers to materials that become less viscous when subjected to pressure or stress—like ketchup that won't come out of the bottle until you shake it forcefully 1 2 .
The FG/MCC composites exhibited excellent shear-thinning properties, meaning they flowed easily through the printing nozzle when pressure was applied but immediately regained their viscosity once deposited, holding their shape perfectly.
| MCC Content | Optimal Printing Temperature | Shear-Thinning Behavior | Structural Stability |
|---|---|---|---|
| Low | Lower temperature required | Moderate | Limited shape retention |
| Medium | Moderate temperature | Enhanced | Improved layer stacking |
| High | Higher temperature needed | Pronounced | Excellent structural definition |
| Excessive | Printing failure | Overly viscous | Microcracks and defects |
While creating precise 3D patterns is impressive, the ultimate test of a bioink lies in its ability to support biological functions. The research team thoroughly investigated how MCC content influenced key scaffold characteristics that determine biological performance 1 2 .
The swelling behavior and degradation rate of the scaffolds could be modulated, ensuring the temporary support structure would break down at an appropriate pace as native tissue grows.
Swelling Behavior: Affects material interaction with bodily fluids and nutrients.
Degradation Rate: Critical for matching tissue regeneration pace.
Pores facilitate cell migration and provide surface area for cell attachment, both critical for tissue development.
Cell Migration
Cell Attachment
Nutrient Exchange
Advanced chemical analysis revealed why the FG/MCC combination worked so well together. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of hydrogen bonds between MCC and FG molecules 1 4 .
These molecular-level interactions explain the enhanced mechanical properties of the composite—the two materials aren't just physically mixed but form intimate connections that create a structure stronger than either component alone.
X-ray diffraction (XRD) further demonstrated how the crystalline structure of MCC contributed to reinforcing the gelatin matrix, providing scientific evidence for the observed improvement in compressive strength 1 .
Hydrogen bonds between FG and MCC create enhanced mechanical properties.
| Research Area | Main Finding | Significance |
|---|---|---|
| Printability | MCC content determines optimal printing temperature | Enables precise parameter control for high-fidelity printing |
| Rheology | Composites exhibit shear-thinning behavior | Confirms suitability for extrusion-based printing |
| Mechanical Properties | Compressive strength increases with MCC content | Addresses gelatin's historical weakness as a bioink |
| Scaffold Architecture | Porosity decreases with increasing MCC content | Allows tuning of scaffold properties for specific tissue types |
| Biological Compatibility | Hydrogen bonds form between FG and MCC | Explains enhanced properties through molecular interactions |
While the FG/MCC bioink system shows tremendous promise, the research represents just the beginning of the journey toward clinical application.
The promising results from similar fish gelatin-based bioinks are encouraging—one study using fish-derived methacrylated gelatin with cellulose nanofibrils showed high viability and proliferation rates for human adipose stem cells 8 .
The development of fish gelatin and microcrystalline cellulose biomaterial inks represents more than just a technical achievement—it exemplifies a broader shift toward sustainable, ecologically conscious biomedical engineering.
By transforming fishing industry byproducts into valuable medical materials and combining them with plant-based reinforcements, researchers have created a bioink that's not only effective but also responsible.
This research pushes us closer to a future where personalized tissue implants can be printed on demand, where drug testing occurs on manufactured human tissues rather than animals, and where the organ donor shortage becomes a thing of the past.
The humble origins of these materials—fish skins and plant cells—remind us that sometimes the most advanced solutions come from understanding and emulating nature's wisdom.