Making bones with a XNUMXD printer

To make an implant that can replace missing bone parts, simply mix 30% of crushed natural bone together with a special type of plastic and create the required shape using a XNUMXD printer 

[Translation by Dr. Nachmani Moshe]

To make an implant that can replace missing bone parts, simply mix 30% of crushed natural bone together with a special type of plastic and create the required shape using a XNUMXD printer. This successful recipe was followed by researchers from Johns Hopkins University and published as an article in the scientific journal ACS Biomaterials Science & Engineering.

Every year, the researchers say, birth defects, severe injuries and surgeries leave about two hundred thousand patients who require bone replacement in the head or face. Normally, the recommended treatment until now required the surgeons to remove part of the patient's tibia (one of the two shin bones), cut it to the appropriate general shape and implant it in the desired location. However, explains biomedical engineering professor Warren Grayson, the procedure not only creates trauma to the leg but is sometimes inappropriate since the relatively straight tibia cannot be shaped into shapes that include a curved and concave outline. This limitation led the researchers to XNUMXD printing, or what is known today as "additive manufacturing", which allows the production of XNUMXD objects from a digital computer file by injecting extremely thin layers of suitable materials.

The process excels at making extremely precise structures - including anatomically precise structures - from plastic, but "cells placed on plastic surfaces need a certain direction in order to become bone cells," explains the researcher. "The ideal scaffold is actually another piece of bone, but usually natural bones cannot be designed in a completely precise way." As part of their experiments, the researchers intended to prepare a composite material that could combine the strength and printing ability of plastic together with the biological "information" stored in natural bone.

The researchers started with the material polycarfolketone (PCL), a biodegradable polyester used in making polyurethane that has been approved by the US Food and Drug Administration for other medical uses. "The PCL material melts at a temperature of 100-80 degrees Celsius - a temperature range that is significantly lower than most other types of plastic - so it is a suitable material for mixing with biological materials that may be damaged at higher temperatures," explains one of the researchers. The material is also quite strong material, but the researchers knew from previous studies that it does not adequately support the creation of new bone. In order to solve the problem, they mixed it with increasing amounts of "bone powder", which they got from breaking up the porous bones found in the legs of cows after removing the tissues and cells from those bones. "Bone powder includes structural proteins suitable for the body along with growth factors that help immature stem cells develop into bone cells," explains the lead researcher. "The powder also adds roughness to the PCL material, a property that helps cells adhere to surfaces and increase the role of growth factors."
The first test the new materials passed was their ability to be printed, explains the researcher. Mixes with 5, 30, and 70 percent bone meal performed as expected, but a mix with 85 percent bone meal contained too little of the PCL adhesive to preserve the sharp crystalline structure, so this mixture was no longer used in the ongoing experiments. In order to test whether the scaffolds are able to encourage bone formation, the researchers added human stem cells taken after liposuction surgeries. After three weeks, cells grown in the mixture of 70% bone powder showed hundreds of times higher genetic activity within three genes related to bone formation, compared to cells grown on clean scaffolds. For the 30% mixture, the bone powder scaffolds showed less good results.

After the scientists added the key component - beta-glycerophosphate - to the cell mixture in order to allow the enzymes to cause the deposition of calcium, the main mineral in bones, the mixtures produced double the amount of calcium compared to original scaffolds. In the final step, the researchers tested their scaffolds in mice with fairly large holes deliberately made in their skull bones. Without any intervention, the wounds were actually too big to heal. Mice treated with scaffold implants that were packed with stem cells were able to grow bone cells inside the holes during the 12 weeks of the experiment. "In both experiments, the scaffold with the 70% mixture encouraged bone growth much better than the scaffold with the 30% mixture," says the researcher, however, the second mixture is much stronger. In light of the fact that there was no difference between the two scaffolds in terms of the ability to heal the skull bone of the mice, the researchers continue to study the mixtures to find which of the mixtures is the most effective.

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A sample of a bone scaffold printed with a XNUMXD printer [Courtesy: Johns Hopkins Medicine]