AI-enhanced 3D bioprinting enables custom oral soft-tissue grafts

The researchers utilised 3D bioprinting to produce grafts precisely matched to individual defect geometries. They developed a specialised bioink capable of supporting healthy cell growth and from which an accurate graft could be printed that would retain its structure and integrity.

Given the complexity of factors that influence the qualities and performance of the printed grafts—such as extrusion pressure, printing speed, nozzle size, bioink viscosity and print head temperature—the team incorporated AI into their workflow to adjust these parameters, which would otherwise involve time- and resource-consuming trials. “This approach greatly streamlines the process by reducing the number of experiments needed to optimise the bioprinting parameters—from potentially thousands to just 25 combinations,” co-author Prof. Dean Ho, head of the Department of Biomedical Engineering in the College of Design and Engineering at NUS, said in a press release.

The resulting bioprinted gingival tissue grafts displayed strong biomimetic characteristics. They maintained over 90% cell viability both immediately after printing and throughout an 18-day culture period. In addition to the grafts preserving their shape and structural stability, histological analyses confirmed the presence of key proteins and a multilayered architecture closely resembling that of natural gingival tissue.

“Our study is among the first to specifically integrate 3D-bioprinting and AI technologies for the biofabrication of customised oral soft-tissue constructs,” said co-author Dr Gopu Sriram, assistant professor at the NUS Faculty of Dentistry. He added: “3D bioprinting is by far more challenging than conventional 3D printing because it involves living cells, which introduce a host of complexities to the printing process.”

The research holds promise for addressing long-standing clinical challenges related to periodontal treatment and dental implant procedures. “This research demonstrates how AI and 3D bioprinting can converge to solve complex medical problems through precision medicine,” explained Dr Sriram. “By optimising tissue grafts for individual patients, we can reduce the invasiveness of dental procedures while ensuring better healing and recovery.”

Broader applications in regenerative medicine

Beyond dentistry, the research has implications for other fields of regenerative medicine. The insights gained may support the development of grafts for other barrier tissues, such as skin, potentially contributing to scarless wound healing. “3D bioprinting allows us to create tissue grafts that precisely match the dimensions of a patient’s wounds, potentially reducing or eliminating the need to harvest tissue from the patient’s body,” Dr Sriram commented.

Co-author Dr Jacob Chew, an associate consultant in periodontics at the National University Centre for Oral Health, Singapore, commented: “This level of customisation minimises graft distortion and tension during wound closure, reducing the risk of complications, surgery time and discomfort to the patients.”

The team plans to conduct in vivo studies to evaluate the integration and stability of the grafts in oral environments. They also aim to enhance the grafts’ functionality by integrating vascular networks via multi-material bioprinting. These advances could not only revolutionise regenerative dentistry but also lay the groundwork for broader applications in tissue engineering.

The study, titled “3D bioprinting and artificial intelligence-assisted biofabrication of personalized oral soft tissue constructs”, was published online on 17 December 2024 in Advanced Healthcare Materials, ahead of inclusion in an issue.

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