The inside track on 3D-bioprinting

Is it better to be on the outside looking in, or on the inside? One research team certainly thinks the latter.

In Westworld, Sir Anthony Hopkins’ character Dr Robert Ford describes 3D-bioprinting as being able to “slip evolution’s leash”. We might not be there yet, but bioprinting can already reproduce prosthetics, orthopaedic joints, bone, skin, organoids and vasculature. The printing is done in the lab and then implanted, but what if it could be done in the clinic – actually inside the patient?

Longevity.Technology: We have covered before just how desperately replacement organs are needed. 3D-bioprinting has serious potential as a regenerative technology. Longevity companies are beginning to respond to this need and the global bioprinting market is expected to reach $4.1bn by 2026 [1]. Approaching this from a non-invasive direction is a smart way to accelerate progress in this field.

Generating 3D-bioprinted tissue in the lab and then implanting into a patient means invasive surgery, which brings increased risk of infection and extended recovery time. These factors, coupled with the issue that a patient’s body is constantly changing, led a team from the Terasaki Institute, Ohio State and Pennsylvania State University‘s to investigate whether a specially-formulated bio-ink, designed for printing directly in the body, could be created.

In a lab setting, some bioprinted tissue is solidified by the application of dangerous UV light; the team needed to develop an ink that could react to normal light, as well as working well at body temperature (37°C) while bonding effectively to working, live tissue.

3D lattice structure of a tissue implanted directly onto a soft living tissue. Credit: Ohio State University
Using light and a unique printer head to create a 3D lattice structure of a tissue implanted directly onto a soft living tissue. Credit: Ohio State University

The research team developed a “specific formulation of gelatin methacryloyl (GelMA)/Laponite®/methylcellulose (GLM) biomaterial system [2].” This material could effectively be 3D-printed at body temperature and cross-linked using visible light.

A 3D robotic printer was used to precisely dispense bio-ink through a nozzle tip that was modified to penetrate soft tissue; it created an anchor point for the newly-constructed bio-printed tissue, and then once it had withdrawn to the surface, it dispensed an additional blob of bio-ink which “locked in” the anchor.

Workflow for internal 3D bio-printing Credit: Ohio State University
Workflow for internal 3D bio-printing Credit: Ohio State University

The team were able to construct 3D tissue-engineered scaffolds that demonstrated clinically-relevant dimensions and consistent structures. Cell viability was reported to be 71-77%, with mechanical properties that were consistent over a 21-day period. The team also found there was a near 4-fold increase in the biomaterial/tissue adhesion strength compared with printing on top of the tissue.

First author of the study, Ali Asghari Adib, PhD, of Ohio State, said: “This bio-ink formulation is 3-D printable at physiological temperature, and can be crosslinked safely using visible light inside the body … The interlocking mechanism enables stronger attachments of the scaffolds to the soft tissue substrate inside the patient body [3].”

Ali Khademhosseini, PhD, Director and CEO of the Terasaki Institute, said: “Developing personalized tissues that can address various injuries and ailments is very important for the future of medicine. The work presented here addresses an important challenge in making these tissues, as it enables us to deliver the right cells and materials directly to the defect in the operating room [4].”

[4] Ibid

All images courtesy of Ohio State University