Breakthrough in 3D bioprinting technology for controlled bone regeneration

19 August 2020

Researchers at AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research, the Trinity Centre for Biomedical Engineering at Trinity College Dublin have developed a new technology to support bone regeneration. Their work presents a step change over current medical interventions in regenerative medicine and opens the door to new therapies to treat substantial fractures and other diseases.

The team have developed a printable ‘bioink’ that enables bone, and its’ supporting blood vessels, to grow in a controlled way and have tested their technology in laboratory preclinical studies. The team have optimised the bioink so that the important growth factors contributing to the natural process of fracture repair and tissue regeneration can be released inside the body in a controlled way, where, and when, they are most needed.

The great potential and problems facing regenerative medicine

A revolution in healthcare through personalised and regenerative medicine is heralded as a key vehicle by which healthcare systems can achieve better outcomes for patients while also helping achieve financial efficiency across the health system. While great therapeutic advances have been made, problems still exist in maximising the potential for regenerative medicine for patients. One key issue facing clinicians has been the ability to deliver specific cues to the body, at the site of disease, to enable the growth of complex tissues such a bone, which also requires integration of blood vessels and nerves to operate in a normal manner.

Despite the tremendous potential of growth factor delivery as a therapeutic mechanism, the results obtained in larger clinical trials have not always shown the expected benefit to patients, with some studies reporting drastic adverse side-effects¹. One potential reason for these complications is that the current best practice is to deliver concentrations of growth factor which greatly exceeds normal concentrations in the body. This method neglects the very sensitive complex role of growth factors in tissue regeneration whereby, as new bone and its associated vessels re-grow, different growth factors, at different concentrations, and at different sites within the damaged tissue are required. A more sensitive, controlled, delivery mechanism that takes into account these requirements is needed to maximise therapeutic outcomes.

Advancing a controlled treatment for bone and tissue regeneration

The team focused their attention on solving the problem of controlled growth factor delivery, so that the correct growth factors could be delivered where, and when, they were needed. The team succeeded in developing an approach using 3D bioprinting techniques and funtionalised bioinks to 3D print constructs that contain patterns of growth factors. This pattern is crucial, as it provides the body the necessary cues to regenerate bone itself over time and at specific sites in the injury. Their research allows for controlled tissue regeneration limiting risk of adverse side effects from current approaches and has been published in the high-profile journal Science Advances

Lead researcher on the project, Dr. Fiona Freeman, Marie Curie Fellow in the Trinity Centre for Biomedical Engineering at Trinity College Dublin and Harvard Medical School says “This study demonstrates the potential of growth factor printing as a point of care therapy for tightly controlled tissue regeneration. This approach overcomes many of the challenges associated with cell-based therapies by providing the body the necessary cues to regenerate itself rather than implant replacement tissue, or flood the body with excessive levels of growth factors to support regeneration”.

Prof. Daniel Kelly, AMBER researcher and Chair of Tissue Engineering at the Trinity Centre for Biomedical Engineering, Trinity College Dublin who over saw the study says “We have demonstrated a potential clinical utility in the regeneration of large bone defects or the increased vascularization of any 3D printed construct. Our Proof-of-Concept studies established the potential of these growth factor loaded bioinks to induce bone regeneration and vascularisation. The benefit of this precise localization of growth factors in both time and space is that it allows for tightly controlled new tissue formation, thereby reducing off-target effects”.

The team envision that this platform technology could be applied to the controlled regeneration of numerous different tissue types. The next stage of this work is to incorporate it with current on-going cartilage regeneration strategies being developed in Prof. Kelly’s lab to develop 3D bioprinted constructs for the repair of osteochondral defects. The study was jointly funded by the European Research Council (ERC) and the Irish Research Council