EPFL develops 3D printable bone scaffold using enzyme-driven mineralization
Room-temperature process produces load-bearing scaffolds within seven days
Researchers at the École Polytechnique Fédérale de Lausanne (EPFL) have developed a method to 3D print porous scaffolds made from hydroxyapatite (HA), which is the primary mineral component of bone.
The process occurs at room temperature and is driven by naturally occurring enzymes, and the resulting scaffolds can bear the weight of an adult human within four days of mineralization. They then become fully load-bearing within seven days.
Bone tissue engineering encounters issues with conventional HA-based scaffold production as a result of its high-temperature processing requirements, which consume significant energy and prevent the incorporation of biologically active components such as enzymes.
The EPFL team has developed a printable and injectable ink that sidesteps these constraints.
Engineering space for bone remodeling
The ink is produced by embedding the enzyme alkaline phosphatase into gelatin microparticles. These are then incubated in a calcium and phosphate ion solution, and the enzyme triggers HA crystal formation, which stiffens and strengthens the printed structure.
After four days of mineralization, the composite can support the average weight of an adult human across an area of just 1.5 centimeters by 1.5 centimeters.
The team also incorporated enzyme-free gelatin microfragments into the scaffolds. These melt during incubation, leaving behind pores that can be colonized by healthy cells following implantation at a fracture site. The pore density is tunable – the researchers configured pores to occupy roughly 50% of the scaffold volume to allow for cell infiltration and bone remodeling.
“Our idea was to generate a 3D printable and injectable ‘ink’ that can be mineralized into scaffolds with mechanical properties similar to those of highly porous trabecular bone, which is found in human vertebrae and the ends of long bones like the femur,” said Esther Amstad, head of the Soft Materials Laboratory at EPFL.
“We hope that our technology’s combination of mechanical performance, bioactivity, and energy-efficient processing will open new avenues for bone tissue engineering.”
In one experiment, the researchers detected collagen and the bone matrix protein osteocalcin — both indicators of cell growth — 14 days after seeding scaffolds with human stem cells in a bone growth-supporting medium.
The SMaL team also reported that their enzyme-aided HA scaffolds exhibited compressive strength comparable to human trabecular bone, and that performance was better than scaffolds produced via high-temperature methods. The technique is also compatible with commercially available bioprinters.
“Looking ahead, our work might lay the foundation for injectable scaffolds that aid bone regeneration and potentially enable patients to load their broken bones much earlier than can be achieved with currently available technologies,” Amstad concluded.
