Laser technique produces synthetic tissue for regenerative medicine

Ashley N. Paddock, ashley.paddock@photonics.com

Tissue that has been damaged by disease or trauma often cannot repair itself. However, a new picosecond laser technique produces biomimetic matrices that allow the body to regenerate itself using the patient’s own cells.

The process was developed by researchers at the Fraunhofer Institute for Laser Technology ILT and other Fraunhofer institutes. The biomimetic scaffolds closely emulate endogenous tissue and enable fabrication of specialized model systems for studying 3-D cell growth. The researchers combined organic substances with polymers to produce 3-D structures that are suitable for building artificial tissue.

Capillaries of an artificial resilient polymer with a diameter of 20 µm. Images courtesy of Fraunhofer Institute for Laser Technology ILT.

“Tissue engineering is a highly interesting and versatile research area with huge application potential,” said Sascha Engelhardt, project manager at ILT. “However, scaffolds developed for tissue engineering are not yet fully able to mimic their complex natural models.”

Normally, scaffold production is focused either on structural, mechanical or biochemical aspects, but Engelhardt explained that all three must be considered in a single scaffold because they all have been shown to influence cell behavior significantly.

“By controlling structure, mechanics and biochemistry in a single experiment, the complexity of the natural model can be reduced to its essentials,” he said. “From this gained knowledge, a translation in a technical solution will be more feasible.”

The researchers used dissolved endogenous proteins – such as albumin, collagen and fibronectin – and polymers irradiated with laser light and cross-linked by photolytic processes. To achieve this, they deployed picosecond laser pulses from a low-cost microchip laser to trigger a multiphoton polymerization process. The short pulse duration caused almost no heat damage to the material. Ultrafast megawatt-range pulses drove a massive number of protons into the laser focus in an extremely short time, triggering a nonlinear effect.

Test matrix consisting of a polymer support structure and a protein functional structure.

The molecules in the liquid absorbed several photons simultaneously, causing free radicals to form. This multiphoton polymerization process triggered chemical reactions between the surrounding molecules, forming solids from the liquid. CAD data helped the system guide the position of the laser beam through a microscope with the precision of a few hundred nanometers in such a way that micrometer-fine, stable volume elements of cross-linked material gradually formed.

With resolution of approximately 1 µm, the process enabled the team to produce cell scaffolds directly from dissolved proteins and polymers, Engelhardt said. Offering much greater stability, the scaffolds can be seeded with the patient’s own cells in a medical laboratory, and then the colonized scaffolds can be expected to produce good implant growth in the patient’s body. The long-term aim is to produce not only individual cell colonies but also artificial tailor-made organs.

“Our next aim will be to design and develop an in vitro assay in the form of a controlled 3-D microenvironment based on our technology,” Engelhardt said. “Of course, this assay will not be realized alone by our institute, but within an interdisciplinary cooperation of research partners. Our long-term goal is to upscale our approach by increasing the process speed.”

To reduce the time and cost of producing tailor-made supporting structures for synthetic tissue, the team wants to combine its fabrication process with other rapid prototyping methods.