Laser Technique Developed for Microscale Tissue Engineering

Array of microneedles (Biomedical Optics Express)

A research team from Laser Zentrum Hannover (LZH) eV Institute in Hannover, Germany, and the Joint Department of Biomedical Engineering at University of North Carolina at Chapel Hill and North Carolina State University in Raleigh has devised a technique to produce finely detailed scaffolds on which human cells can grow to replace lost or damaged tissue. The team’s findings appear online in the 1 November issue of the journal Biomedical Optics Express.

The goal of tissue engineering is to create living structures that could replace lost or damaged tissue, but the manufacture of the detailed frameworks or scaffolds where human cells can grow to create the replacement tissue has been a significant challenge that has kept most tissue engineering applications confined to the research lab. The LZH/North Carolina research team, however, has found a way to extend a manufacturing technique called two-photon polymerization (2PP) that creates intricate structures such as tissue scaffolds more quickly and efficiently.

The 2PP process occurs at the microscale level, where 1 micrometer or micron equals 1 millionth of a meter. Current 2PP technology involves a laser pulse that lasts approximately one quadrillionth of a second that sends an energy burst into unset resin, causing the molecules around the pulse to fuse together into two adjoining cone shapes. By focusing on multiple points in succession, 2PP can build up complex 3D structures, one cone-shaped block at a time.

While this process is detailed and precise, it is also slow — too slow, in fact for biomedical applications. The LZH/North Carolina research team needed to find a way of engaging this finely detailed  construction process, but at higher speeds required for clinical use. The team overcame this obstacle with a computer-controlled hologram to split the 2PP laser into multiple beams, creating up to 16 different focus points that can work simultaneously.

The paper reports that the conventional fabrication time for a single layered, 1-millimeter square with 100 nanometer resolution was 2 hours and 47 minutes, with a single-focus 2PP process. Using the hologram-enhanced, 16 foci process, the team cut the production time for the single layered, 1-millimeter square to about 10 minutes.

To demonstrate the concept, the research team created a panel with 16 microscopic replicas of the Venus statue. On a more practical biomedical level, the researchers later manufactured cylindrical tissue scaffolds and an array of microneedles measuring less than a half millimeter wide (pictured at top). Microneedles of this kind could be used to provide painless injections or take blood samples.

Read more: Nanotech Patch Repairs Damaged Heart Tissue in Lab Tests

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