A new ‘sono-ink’ developed by researchers at Duke University and Harvard Medical School may one day allow 3D printing of structures deep inside the human body. This ultrasound-sensitive bio-ink solidifies when targeted with focused soundwaves, creating intricate scaffolds that could aid tissue repair and regeneration.
Traditional 3D printing builds objects layer-by-layer, limiting speed and increasing complexity. In order to use bio-inks in therapeutics application deep inside tissues, the ink must be injected into the target location and then hardened. This can be applied for bone healing and heart valve repair.
While light-sensitive bio-inks can harden when exposed to targeted light beams, the ability of light to penetrate human tissue is poor. To resolve these issues, the researchers developed a new 3D printing technique known as deep penetrating acoustic volumetric printing (DAVP). It uses a special bio-ink made of hydrogels, particles, and molecules that harden in response to specific ultrasound frequencies.
“DAVP relies on sonothermal effect, which occurs when soundwaves are absorbed and increase the temperature to harden our ink,” explains Dr Junjie Yao, associate professor of biomedical engineering at Duke. “Ultrasound can reach over 100 times deeper than light, enabling previously unreachable inner tissues and organs to be precisely targeted,” he points out.
Sono-ink is highly flexible
Once delivered to the target area, focused ultrasound waves harden the sono-ink into intricate structures like hexagonal scaffolds that can mimic the hardness of bone. Another potential use is to produce a bubble of hydrogel placed over an organ, which can then be used for targeted drug delivery.
“The ink itself is a viscous liquid and it can be injected into a targeted area easily. As the ultrasound printing probe is moved around, the materials in the ink will link together and harden,” says Dr Yu Shrike Zhang, associate professor, department of medicine, Harvard Medical School. Once it is done, any remaining ink that is not solidified can be removed via a syringe, he says.
The components of sono-ink can be modified for a wide variety of uses. For example, bone mineral particles can be added to it for producing a scaffold that helps in healing a fractured bone or make up for loss of bone. Depending on the requirements, the structure produced can be engineered to be more durable or biodegradable. “The printed structures can firmly attach to the tissue surface even under reasonable stretching and twisting. We are able to design these sono-inks precisely for matching the intended tissue types,” says Dr Zhang.
Proof of concept
To test their new technique for real-world applications, the team produced various structures as a proof of concept. First, the ink was used to seal off a section in an isolated heart of goat known as left atrial appendage. The sono-ink was delivered to the left atrial appendage where it was hardened by focused ultrasound waves, without affecting the nearby tissue. After this, the ink was safely bonded to the heart tissue, proving quite flexible and capable of withstanding movements mimicking a beating heart.
The demonstration shows potential for the treatment of nonvalvular atrial fibrillation, in which irregular heartbeat causes blood to pool in the left atrial appendage. In such conditions, the left atrial appendage must be sealed to lower the risk of blood clot and heart attack, necessitating an open chest surgery. The new bio-ink method could negate the need for risky open-chest surgery.
Next, this technique was used for reconstruction and regeneration of tissues. They created a bone defect model in a chicken leg in which portion of bone was removed and then the sono-ink was injected. It was hardened using ultrasound waves through skin and muscle tissue layers. The resulting scaffold bonded with bone seamlessly without affecting the surrounding tissues.
Sono-ink was also used for creating a hydrogel for drug delivery. The team added a common chemotherapy drug into the sono-ink and injected it in sample liver tissue. With ultrasound waves, the sono-ink was hardened into hydrogel which releases drug slowly and diffuses into liver tissue.
Future course
“Because we can print through tissue, it allows for a lot of potential applications in surgery and therapy that traditionally involve very invasive and disruptive methods,” said Dr Yao. This work opens up an exciting new avenue in the 3D printing world, he adds.
“However, we are still far from bringing this tool into clinic as there are still challenges associated with current version of this technology. The challenges include further optimisation of sono-ink for a wider range of materials, enhancing the precision and resolution of printing process, and ensuring biocompatibility and safety for in-vivo applications. We are hopeful that this will happen in the next decade,” says Dr Zhang.
