New temperature-controlled 3D-printing bioink safer for artificial organs
3D bioprinting is gaining popularity as a way of treating disease and injury by producing three-dimensional living tissues and organs. However, to work effectively, the “inks” used for bioprinting must be firmed up using UV light or chemical processes. But now researchers have developed a new bioink that hardens in response to body temperature, making it safer for potential use in artificial organs and tissue regeneration applications.
Bioprinting uses 3D-printable bioinks, substances – usually containing cells – that cause the body to elicit a biological response aimed at tissue regeneration. Bioinks must have particular mechanical and biological properties to be used in extrusion-based bioprinters due to the high stresses of the 3D-printing process. They also need to be biocompatible and biodegradable.
Current hydrogel-based bioinks must undergo a photocuring process before being used in the body. Photocuring causes crosslinking, the formation of strong, permanent covalent bonds between polymer chains in the hydrogel that increases its mechanical strength and stability under physiological conditions. The photoinitiators introduced into the hydrogel to enable photocuring are activated by ultraviolet (UV) light, but UV light can damage the cells’ DNA. Chemical crosslinking, an alternative to photocuring, uses a reagent (crosslinker) to achieve the same result.
Now, researchers from the Korea Institute of Science and Technology (KIST) have developed a new hydrogel-based bioink that can maintain its physical structure without the need for photocuring or chemical crosslinking.
For the first time, the team developed a poly(organophosphazene)-based temperature-sensitive hydrogel that exists in liquid form at low temperatures – meaning it can be printed easily – and hardens at body temperature (98.6 ° F/37 °C) without the need for photocuring or chemical crosslinking.
At near body temperature, the un-photocured 3D bioprint was physically stable and biodegraded into nontoxic materials. In addition, the researchers demonstrated that the new bioink could be loaded with growth factors that were able to be stored for long periods. These proteins stimulate cell growth and differentiation, the body’s inflammation response, and tissue repair.
The researchers mixed the growth factors bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta 1 (TGF-Beta1) into the bioink and created a 3D scaffold, which they implanted into the damaged skull of a rat. They found that surrounding tissues migrated into the scaffold and promoted the regeneration of normal bone. The scaffold biodegraded slowly over 42 days.
The research team are continuing to develop their bioink for use in tissues other than bone and say it could one day be used in artificial organs.
“As the bioink developed this time has different physical properties, follow-up research to apply it to the regeneration of other tissues besides bone tissue is being conducted, and we expect to finally be able to commercialize bioink tailored to each tissue and organ,” said Soo-Chang Song, corresponding author of the study.
The study was published in the journal Small.