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Nano-design inspired by nature enables cells to interact with implants

Eye implants that communicate with living cells have the potential to spare many patients from having to undergo further eye surgery or laser treatment. However, Christian Lingenfelder, managing director of Dornstadt-based Alamedics, believes that it will take at least five to seven years for the idea to become reality and a medical product placed on the market. Alamedics, which was founded in 2012, has already made an important initial step in the right direction.

Alamedics has joined forces with two partners from academia and two companies from the region with the aim of developing and implementing active biomimetic structures to control the growth of cells on ocular implants. The German Federal Ministry of Education and Research (BMBF) is providing the BioSurf project with 1.4 million euros in funding for a period of three years. The goal is to develop a prototype within the funding period.

Turning passive surfaces into bioactive surfaces

Dr. Lingenfelder, the project coordinator, explains that the goal of the project is to apply nanostructures on implants such as lenses and stents. Lingenfelder, a human biologist who also has an MBA, envisages a coating that will enable the implanted device and the body to interact effectively, thereby preventing uncontrolled processes and cells from impairing implant function. “We are looking to gain insights into this interaction and use innovative products to control it.” The project seeks to turn passive implant surfaces into bioactive ones by altering the implant surface.

Implants were previously coated with a passive layer of nitrite, nitrate or carbon. "Our layers actually communicate with cells by way of the nanostructures applied to the implant; the height of the structures and the distances between the structures will trigger specific reactions in the cell. Proof-of-concept has been provided by a scientific partner of Alamedics, the Max Planck Institute for Intelligent Systems in Stuttgart. The Department of New Materials and Biosystems led by Joachim Spatz has been able to show that “it is possible to create a kind of maze on a slide using nanostructures, thereby dictating to cells the way to travel from point A to point B.” 

Lingenfelder explains: “The cell explores its environment, stretches out protein filaments and examines the ground to ascertain whether it is suitable for growth. The implant surface communicates virtually with the cell by way of its (transmembrane) receptors. We can make the cell express proteins or divide, amongst many other things.”

Inspired by moth eyes

Scanning electron microscope image of the eye surface of a nocturnal moth (top row). A periodic pattern of protuberances of sub-wavelength size is responsible for the antireflective properties of the moth eye. Artificial moth eye structures can be produced with fused silica (bottom row). Nanoparticles are used as a shadow mask for etching the structures directly into the surface of the material. © MPI IS, Stuttgart

The researchers from Stuttgart have copied the surface treatment from nature: the eye of a nocturnal moth.

The tiny, column-like protuberances on the eye surface stop reflections from occurring that could betray the moth's presence, thus protecting it from predators. The insects are not revealed through a reflection on their compound eyes and can safely look for food and recognise predators at dusk. The tiny columns are smaller than the wavelength of light, so the reflection of the light is considerably reduced. The physical dimension of the biomimetic structures increases transmission, i.e. the amount of light that enters the optical system. This allows the development of highly refractive, very thin materials.

The project involves the use of moth-eye structures, tiny nanoscale columns which vary in height and distance. The researchers are also studying the effect such columns have on cells. The coupling of proteins enables these nanostructures to interact with the cell. 

The BioSurf project is focused on investigating and developing implants that strongly inhibit, or in the ideal case scenario completely prevent, the growth of epithelial cells on eye implants, thereby providing patients with uncompromised vision following implantation. Vision problems can be very costly for healthcare systems. In addition to diseases, it is age-related factors in particular that can compromise vision or even lead to loss of vision.

Age-related eye diseases are of crucial importance in the health economy

In contrast to many other common diseases, age-related eye diseases are increasingly affecting people’s health, especially glaucoma and age-related macular degeneration (White Paper of the German Association of Ophthalmology, p. 6). In Germany, millions of people have vision problems. The White Paper estimates that around 2.2 million people suffer from glaucoma (early stages included) and around 9.8 million people from cataracts. Around 650,000 people need cataract surgery every year in Germany.

In cataract surgery, the cloudy natural lens is removed from the eye and replaced with an artificial one. The surgical replacement of the natural lens is routine in Germany. However, cataract surgery only provides short-term improvement; vision deteriorates in around half of the patients treated a few years after surgery due to secondary clouding that occurs behind the artificial lens. This clouding is the result of the uncontrolled growth of cells that prevent light from entering the eye. Light incidence changes and visual acuity decreases, requiring post-treatment with lasers or a second surgical intervention.

Glaucoma is another common eye disease which, when left untreated, damages the optic nerve and can lead to blindness. It is caused by increased intraocular pressure that develops from aqueous humour (chamber water) build-up in the eye. An effective therapy is the implantation of a channel-like stent that supports the discharge of the liquid and prevents high intraocular pressure from building up. Glaucoma surgery comes with similar problems to cataract surgery: uncontrolled cell growth clogs the implant, prevents the discharge of the fluid and requires another surgical intervention.

BioSurf project members (from left to right): Dr. Friedrich Offenhäuser (Offenhäuser & Partner); Prof. Dr. Joachim Spatz, Dr. Christoph Morhard (both at the MPI), Nadine Hagedorn, Frederik Wintermantel (both at Alamedics); WenWen Chen, MPI; Dr. Martin Udart (ILM) and project coordinator Dr. Christian Lingenfelder (Alamedics).
BioSurf project members (from left to right): Dr. Friedrich Offenhäuser (Offenhäuser & Partner); Prof. Dr. Joachim Spatz, Dr. Christoph Morhard (both at the MPI), Nadine Hagedorn, Frederik Wintermantel (both at Alamedics); WenWen Chen, MPI; Dr. Martin Udart (ILM) and project coordinator Dr. Christian Lingenfelder (Alamedics). © Alamedics

Successful developments might lead to technological platform

If BioSurf is successful and it is possible to develop surface-modified implants, glaucoma and cataract patients have a good chance of not having to undergo post-treatment/second surgery. Dr. Lingenfelder envisages that the approach might be turned into a new technology platform and also be used in other medical areas such as cardiology and orthopaedics. Moreover, the project also has a research-political dimension as it has the potential to increase the competitiveness of the German medical technology industry. 

Scientific BioSurf partners are: The Stuttgart-based Max Planck Institute for Intelligent Systems with Joachim Spatz, head of department and renowned for his achievements in studying the interaction between biological systems and artificial surfaces. As part of the project, the ILM Institute for Laser Technologies in Medicine and Measurement Technology, which is affiliated with the University of Ulm, will investigate the interaction of living cells and implant surfaces. The Heidenheim-based company Offenhäuser + erger, which specialises in laser protection technology, innovative optics and optical filters, will work with Dornstadt-based Alamedics and implement the different steps of the production process. In addition, Offenhäuser + Berger has plans to specifically focus on the processing of materials and establish this as new field of business. 

Lohmüller, T,  Aydin, D.: et al Nanopatterning by block copolymer micelle nanolithography and bioinspired applications, in: Biointerphases 6 (1), March 2011 DOI: 10.1116/1.3536839

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/nano-design-inspired-by-nature-enables-cells-to-interact-with-implants