A group of researchers at the National University of Singapore has developed a novel method of bioprinting that overcomes some of the limitations of already-existing methods, as well as avoiding damage to the printed tissue. The research has been published in an article entitled “Effective Light Directed Assembly of Building Blocks with Microscale Control,” which you can access here. As the researchers explain, small structures are often moved and assembled using optical tweezers, or lasers capable of directing micro- or nanoscale objects into functional assemblies. The problem is that the intensity required of the lasers to perform the task can be damaging to biological material and result in limited throughput.

The researchers took a different approach, using gold nanorods to act as photothermal transducers, allowing for the assembly of 3D structures using a much lower-powered laser. The gold nanorods, or GNRs, were suspended in fluid to generate thermoplasmonic convections for microfluidic assembly.

“Because significant local thermoplasmonic convections were generated by precisely controlling the low-power infrared laser spot size and direction, effective building block assembly with high resolution enabled the desired patterns,” the researchers explain. “By using an automatic motorized stage with optical source integration, the assemblies with desirable patterns were approached with programmable manner. This method was used as an advanced printing technology to form centimeter-scale functional units in ≈10 min by integrating various hydrogel building blocks, which were fabricated using droplet-based microfluidics. It is worth to note that because this light-directed assembly process was independent of the fabrication of the building blocks, a wide range of functional biocompatible materials could be selected to fabricate the building blocks that form the desired structures without the limitations of polymerization during construction inherent to printing.”

The method allowed for high throughput as well as a high level of precision, thanks to the ability to control the laser spot size and direction. The researchers were able to pattern and rapidly assemble a large number of building blocks, using a bottom-up method. Microparticles seeded with mesenchymal stem cells (MSC) were used to create functional units for 3D cell culture, which showed a high level of cell viability and proliferation.

“Moreover, because a low-power NIR laser was used to induce the GNR thermal convection, this method is suitable for biomedical engineering, including surgical operations and in vivo applications such as the elimination of a preshaping scaffold and prevention of contamination, as well as reagent delivery and precise cell deposition,” the researchers continue. “With the capability of precisely controlled high-throughput building-block assembly, a broad array of applications is expected, ranging from 3D bioprinting to regenerative medicine, tissue engineering, bottom-up manufacturing and biofabrication.”

A patent for the technology has been filed in the US by first author Dinh Ngoc Duy, PhD student, Department of Biomedical Engineering, National University of Singapore, who shared the work with us.

“The future work is functioning building blocks with linker as DNA, which allows to connect building blocks by temperature,” he tells 3DPrint.com. “This bottom-up method of building block assembly can revolutionize current biofabrication processes that otherwise would have been difficult to achieve using 3D printing and other assembly technologies.”

Additional authors of the study include Rongcong Luo, Maria Tankeh Asuncion Christine, Weikang Nicholas Lin, Wei-Chuan Shih (of the University of Houston), James Cho-Hong Goh, and Chia-Hung Chen. You can take a look at one of the scaffold-free tissue assemblies below:

Discuss in the National University of Singapore forum at 3DPB.com.

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