A clinician–researcher team at Massachusetts General Hospital has developed a novel approach to direct-volumetric drop-on-demand three-dimensional (3D) bioprinting. The team is using the new technology to grow articular cartilage that is much more functional than previously possible.
“The treatment options we have for full and partial-thickness cartilage loss are less than ideal,” says Brian E. Grottkau, MD, chief of the Pediatric Orthopaedic Service at Mass General. “We are using 3D printing to tackle this and other problems for which we don’t have good solutions.”
Dr Grottkau is collaborating on the tissue engineering advancement with Yong gang Pang, MD, PhD, an orthopaedic surgery researcher in Mass General’s Laboratory for Therapeutic 3D Bioprinting.
“Everyone else is focusing on the shape of the tissue,” Dr Pang says. “But we are focusing
on the function, as well, by micro-controlling the cells during a bioprinting process and preserving their native functions afterward.”
New 3D bioprinting directly controls volume of a bioink
3D printing can be roughly broken down into two categories, explains Dr Pang: con- tact versus non-contact with the surface.
Drop-on-demand 3D printing is a non-contact method, whereby the bioprinter dispenses tiny droplets of material and cells (together called a bioink) that fall into place on the object being printed. These smaller droplets allow for more control than is possible with 3D bioprinters that must touch the printed surface to dispense a bioink.
To improve accuracy and minimize the negative effect of bioink fluctuations during drop-on-demand printing, the Mass General team has developed a new method to directly control the volume of droplets. They use a thin syringe and squeeze out a small droplet of bioink accurately, just outside the needle tip. A puff of air blows the droplet to the surface of the object being printed before the droplet falls due to gravity. This helps ensure accurate volume, even when the physical properties of the bioink fluctuates.
Bioprinting a solution to articular cartilage damage
An upcoming publication will describe the team’s success in bioprinting microspheres of specifically micro-patterned chondrocytes in a matrix to grow into articular cartilage (the smooth, white tissue at the ends of bones that allows joints to move easily). This cartilage can be damaged by disease, injury or normal wear-and-tear, and current ways to treat cartilage loss are not ideal because of the use of scar tissue or autologous chondrocytes that don’t adhere well.
Drs Grottkau and Pang are combining their drop-on-demand 3D printing technology with a special bioink, made of chondrocytes and an extracellular matrix, to tackle the tough clinical problem of damaged articular cartilage. Using the new printing method, they create micro-cartilage-tissues that they deliver into a cartilage defect with a needle. There, the micro-cartilage-tissues coalesce with existing cartilage “just like a jigsaw puzzle” and organically create macro-cartilage starting from 24 hours after delivery, Dr Grottkau says. “That cartilage winds up being indistinguishable from natural cartilage and integrates with the surrounding cartilage and underlying subchondral bone, which has not been done before.”
The team believes the approach has remarkable promise for healing articular cartilage and can also be used to create:
- Liver tissues that can vascularize
- Biological joint replacements for patients with arthritis
- High-throughput drug screening (for example, bioprinting breast cancer tissues and testing the effectiveness of a large number of drugs).
“We decided to prove our mettle in cartilage, which is vexing to solve, but there
are also many other applications,” says Dr Grottkau.
