Repairing damaged cartilage, which allows the smooth motion of joints, can require surgery to implant donor tissue grafts. A potentially better solution would be the fabrication of custom-made graft tissue scaffolds that enable cartilage cells to recolonize damaged areas and produce new tissue. A new bioink devised by researchers could allow just such three-dimensional cartilage tissue scaffolds to be printed at room temperature [Kesti, M., et al., Acta Biomaterialia (2014) DOI: 10.1016/j.actbio.2014.09.033].
The researchers from ETH Zürich and AO Research Institute Davos in Switzerland and INNOVENT in Germany believe they have come up with a novel way to fabricate scaffolds for cartilage repair via a layer-by-layer bioprinting process using specially designed bioinks. Layer-by-layer bioprinting of artificial tissues like cartilage, which has a stratified structure, is a logical choice, say the researchers. But, to date, the bioinks developed for three-dimensional printing have produced very soft structures that weaken over time.
“Scaffold printing has been achieved with other inks including gelatin, alginate, carbohydrate glass, thermoplastics such as polylactic acid, and many more,” says corresponding author Marcy Zenobi-Wong of ETH Zürich. “[But] it is often difficult to get immediate cessation of the ink flow after extrusion, which limits the printing resolution,” she explains.
Instead, the researchers turned their attention to the natural components of cartilage, the polymers hyaluronan (HA) and chondroitin sulfate. In their original form, the precursor solutions to these materials are too liquid and slow gelling to print with, but the researchers found that adding a heat-responsive biocompatible polymer creates a promising bioink. The combination of poly(N-isopropylacrylamide) (pNIPAAM) and HA creates an ink that is liquid at room temperature but solidifies when printed onto a substrate heated to body temperature (37°). To make the scaffolds more durable, even under mechanical compression, a second polymer – hyaluronan methacrylate or chondroitin sulfate methacrylate (CSMA) – can be added, which covalently crosslinks within the HA-pNIPAAM gel to form a network. Cartilage cells can also be added to the precursor solution and distributed through the finished gel. The HA-pNIPAAM support polymer can be removed subsequently with a simple washing step.
“The mix with HA-pNIPAAM opens up a whole range of polymers that can now be printed with good cell viability and good resolution,” says Zenobi-Wong. “HA-pNIPAAM can basically be combined with any crosslinkable hydrogel precursor… [and] serve as a basis for many other bioinks for different tissue engineering applications.”
The researchers are now moving towards printing complex cartilaginous structures, she says, such as the ear, nose, and trachea (or windpipe).
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