The best recipe for 3D-printed replacement bones
Facial and head surgery can require sections of bone to be removed, and doctors often have to harvest material from elsewhere in the body to fill in the gaps. That's not always an ideal situation, and can lead to complications. New research coming out of the Johns Hopkins University could provide an alternative, creating custom-made, 3D-printed implants from a mixture of plastic and bone powder.
The need for replacement facial and head bones is greater than you might think, with an estimated 200,000 people requiring replacement implants as a result of surgery, trauma or birth defects. Traditionally, surgeons remove bone from the patient's leg, cutting it into the shape of the required implant.
Unsurprisingly, that option doesn't always pan out too well, with the straight nature of the leg bone making it difficult to shape effectively. Combine that with the trauma of having part a bone removed from your leg, and it's clear that a better alternative is called for.
In search of a solution, the Johns Hopkins team turned to additive manufacturing, also known as 3D printing. The method, which works by building up of thin layers of material, allows for the creation of custom-shaped three-dimensional objects. In the case of the study, it provides the opportunity for doctors to produce tailor-made, anatomically accurate implants for their patients.
3D-printing usually makes use of plastics, but in order for cells placed on the printed scaffold to know how to properly interact with it, they need a little organic material to be present. With that in mind, the researchers worked to create a composite implant that combines the strength and versatility of the plastic with the biological instructions that the bone provides.
For the man-made component, they used a biodegradable polyester called polycaprolactone (PCL). This was then mixed with bone that had been pulverized to form a powder.
"Bone powder contains structural poteins native to the body plus pro-bone growth factors that help immature stem cells mature into bone cells," said senior paper author Warren Grayson. "It also adds roughness to the PCL, which helps the cells grip and reinforces the message of the growth factors."
The researchers tried different amounts of the two materials, testing mixes with 5, 30, 70 and 85 percent bone powder. The first three of those mixes printed well, but the implant with the highest percentage of bone powder – the 85 percent mix – had too little PCL to maintain the printed lattice structure.
With that mix eliminated, the team then moved on to testing how well the printed scaffolds encouraged bone formation. To do so, they added fat-derived stem cells harvested from liposuction patients to a nutritional solution containing the scaffold.
The results were pronounced, and extremely promising. When compared to a pure PCL scaffold, the 70 percent bone powder implant showed hundreds of times higher activity in genes related to bone formation. The 30 percent scaffold also showed increase in gene activity, but to a lesser extent.
Next, the team added beta-glycerophosphate to the solution, which allows the enzymes in the cells present to start depositing calcium to build bone. The 70 percent solution twice as much calcium as in PCL-only scaffolds, while the 30 percent scaffold produced around 30 percent more.
For the final round of testing, the team implanted the scaffolds into laboratory mice with holes in their skull bones. Once the scaffolds were in place – along with a helping of stem cells – new bone started to grow within the 12 week experiment timeframe. CT scans showed that some 50 percent more bone grew in the bone powder-containing scaffolds than in the PCL-only variant.
While the study makes it clear that mixing bone powder and PCL is definitely effective, there's still some question over whether the 30 or 70 percent mix is better.
"In both experiments, the 70 percent scaffold encouraged bone formation much better than the 30 percent scaffold, but the 30 percent scaffold is stronger," said Grayson. "Since there wasn't a difference between the two scaffolds in healing the mouse skills, we are investigating further to figure out which blend is best overall."
The findings of the research are published online in the journal ACS Biomaterials Science & Engineering.
Source: Johns Hopkins