Researchers at Texas A&M University have developed microscopic sensors that can be embedded directly into 3D bioprinted tissue and monitored using light. The technology could provide a non-invasive way to assess the health of living cells in engineered tissues, medical implants and, potentially, future transplantable organs.
Three-dimensional bioprinting enables researchers to create complex structures from biocompatible materials containing living cells. However, as these structures become larger and more sophisticated, monitoring what happens inside them becomes increasingly difficult. Existing techniques for measuring metabolites can be invasive and may require researchers to penetrate and damage the engineered tissue. The new approach is designed to overcome that limitation by building the monitoring technology into the printed structure itself.
Sensors embedded during printing
Waqas Saleem, who developed the technology alongside Michael McShane and other researchers, created microscopic sensor particles that can simply be mixed with the material before it is printed. The resulting tissue structure therefore contains sensors exactly where measurements are needed. Rather than physically collecting samples, researchers can obtain information by directing light at the tissue. According to McShane, the principle could also work through the skin when the sensors are incorporated into an implant.
The particles are phosphorescent: they absorb light and subsequently emit it again. When illuminated by an inexpensive red LED, their emitted light changes according to their chemical environment. The process takes only milliseconds and can be analyzed using optical equipment.
Measuring oxygen, glucose and lactate
The technology initially measures oxygen because the characteristics of the emitted light vary with oxygen concentration. The researchers can extend this principle to other substances by combining the particles with enzymes that consume oxygen when interacting with particular nutrients. This makes it possible to indirectly measure metabolites such as glucose and lactate. A single flash of red light can consequently provide real-time chemical information without piercing the tissue.
For tissue engineering, this could address an important obstacle to developing larger bioprinted structures. Researchers need to know whether cells throughout an engineered tissue are receiving sufficient nutrients and remaining healthy. Integrated sensors could provide that information repeatedly without damaging the structure being studied. The researchers also see opportunities in drug development. Continuous monitoring could reveal how cells respond to experimental treatments, including whether a drug stimulates healthy cell growth or inhibits cancer cells.
Home monitoring
Although the technology remains at an early stage, its potential applications extend beyond the laboratory. The researchers envisage tiny sensors implanted just beneath the skin to monitor people with chronic conditions such as diabetes or kidney failure. A sensor smaller than a grain of rice could potentially provide measurements without repeated blood testing.
Another possible application is monitoring tissue following transplantation or cancer surgery. Instead of relying on invasive biopsies, clinicians could potentially assess biochemical changes in affected tissue using light. McShane also foresees consumer devices capable of reading implanted sensors. A smartphone-based system could eventually allow patients to hold their phone above an implant to take a measurement. For continuous monitoring, optical technology could potentially be incorporated into a patch worn on the skin.
Such applications will require further development and validation. For now, the researchers see particular value in laboratory research, where non-invasive monitoring could help scientists study living cells in increasingly complex environments. In the longer term, the technology could complement advances in 3D bioprinting by giving researchers a practical way to monitor the viability of increasingly large engineered tissues. According to Saleem, that capability could ultimately contribute to the development of new therapies and, eventually, fully transplantable bioprinted organs.
3D Bioprinting
Last year, researchers at Oregon Health & Science University (OHSU) and partner institutions highlighted how 3D bioprinting, organoids and organ-on-a-chip technologies were creating new opportunities for cancer research. These New Approach Methodologies (NAMs) replicate important human biological processes and can help researchers understand how cancer originates and progresses without relying on animal models.
Using 3D-printed tissues and chip-based systems, scientists can recreate realistic tumor environments and investigate how genetic, cellular and environmental factors influence cancer development. These models could also help identify biomarkers for earlier cancer detection.
One important application is studying the earliest stages of tumor formation, for which patient samples are rarely available. Researcher Haylie Helms uses single-cell 3D bioprinting combined with patient-derived cancer cells to observe these processes. This could reveal why some precancerous lesions remain stable while others develop into aggressive tumors, potentially supporting earlier diagnosis and more personalized cancer treatment.
References
Advanced Functional Materials (research)
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