M. Vehse

Machining of Biocompatible Ceramics with Femtosecond Laser Pulses

Alumina toughened zirconia (ATZ) ceramic com- posites have been machined and structured with ultrashort laser pulses. With this approach the fabrication of various cavity patterns on the surface of the material with high pre- cision becomes feasible. The scope of surface manipulation with femtosecond lasers gives opportunity to adopt the ce- ramic surface to tissue apposition for several different medi- cal applications employing biocompatible ceramics.

Additive Manufacturing of Drug Delivery Systems

New Drug Delivery Devices are produced using Selective Laser Micro Melting (SLμM). In a first approach, hollow micro needles with an inner diameter of 160 μm were manufactured from 316L stainless steel powder. Afterwards, the hollow micro needles were successfully filled with a test liquid. In a second approach, fully dense micro needles with an outer diameter of 200 μm were produced. A femtosecond laser setup was used to create discrete drug depots in fully dense micro needles.

Material Processing with Femtosecond Laser Pulses for Medical Applications

Medical implants require functional surfaces in order to ensure biological compatibility. Micrometer-sized surface structures are needed in particular for a successful adaptation on a cellular basis. Pulsed laser light sources with sub-ps pulse durations are promising tools exceeding the precision in material processing of nowadays mechanical methods. Our three-axis-scanner allows arbitrary focus positioning on the sample for material processing. Intense ultrashort near infrared laser pulses with adjustable pulse envelopes and variable focusing conditions are used for the material ablation. Moreover, process parameters like pulse energy, pulse repetition rate and focusing conditions are adjusted to adapt the laser parameters to the specific requirements regarding geometry and materials in use. Prototype drug depots have been machined by laser surface structuring.

Loading method for discrete drug depots on implant surfaces

Modern biomedical engineering focuses more and more on the development of implant-associated local drug delivery systems for many different applications like stents for the treatment of coronary artery disease. A common method to deposit drugs on implants is their integration within a polymeric coating, which might however be contributor of adverse cardiac events. Moreover, modern implants pursue multimodal and time-controlled approaches, which require more sophisticated drug loading methods. In this context, a loading method based on surface depots that are selectively filled with drugs using a drop-on-demand printhead is investigated. As a first step small drug depots were produced by abrasive or additive laser-based methods on or into the surface of the implant. The range of the depot volumes varies between 1.4x10 5 and 1x10 7 m3. These depots (cavity or tubes) can be filled with pure drugs, drug-polymer-mixtures and/or covered with biodegradable polymers using a piezoelectric drop-on-demand printhead. Therefore, the drugs are dissolved in methanol, ethanol or dimethyl sulfoxide (DMSO). The minimal droplet volume is about 100 pl. The quantity of drug per depot is specified by the number of droplets that are printed into the depots. The proof of principle of the loading method could be demonstrated on stainless steel samples as model implant surface. Drug depots were successfully filled with fluorescein disodium salt, dissolved in a mixture of 50 % DMSO and 50 % ethanol. Further drug depots were loaded with acetylsalicylic acid (ASS), dissolved in pure DMSO. Because of the low volume of a single droplet the depots could be filled very precisely.

Laser structuring of silica surface improves cell adhesion

When implants are required to develop good contact to surrounding tissue the implant surface has to serve as an adhesion substrate for the appropriate cell type. As silica is nontoxic and biocompatible the question arises whether surface modifications will render a surface amenable to cellular adhesion. The silica surface is micro-structured by laser treatment using a frequency doubled Nd:YAG system. Laser treatment strategy and direct laser parameters were varied in order to generate different surface topographies. To test cellular adhesion of silica samples L929 mouse fibroblasts were seeded onto the surface of silica probes. Samples were incubated for 48 h and cell viability was determined by the CellQuanti-Blue assay. Viable cells attached to the silica surface were stained with calcein and visualized by confocal laser scanning microscopy. The silica materials used in this study do not release toxic substances when incubated in aqueous media. Nevertheless, cells seeded onto such silica surfaces show reduced viability when compared to cells seeded onto polystyrene. Confocal laser scanning microscopy reveals that an untreated silica surface does not provide a good cell adhesion substrate whereas a grid surface structure of about 40 μm line space allows cell adhesion. To make silica a substrate for cell adhesion physical surface modification could be a first step. As the pattern is in the micrometer range there might be a need to adjust grid size to target cell size. As a conclusion: laser structuring of silica surfaces improves cell adhesion.

Laser induced surface structure on stainless steel influences cell viability

The interaction of cells and tissue with implant surfaces significantly decides about the reaction of the organism in contact with an implant. The interface between implant and surrounding cell media influences the initiated immune response. An initial point to influence the cell-implant-interaction is to structure the surface of the implant. Laser techniques offer many degrees of freedom to generate micro structures on material surfaces. Using a frequency doubled Nd:YAG laser system, the surface of stainless steel (316L) samples was micro-structured. Micro structures in the range of 20-80 m line width and 10-50 m depth were chosen. Lattice structures, wave structures or nub structures were created on steel plates. L929 mouse fibroblasts were seeded on the plates in order to determine the cell viability and adhesion by confocal laser scanning microscopy. Non-toxic stainless steel (tested in aqueous media) shows significant distinctions in cell adhesion dependent from structure dimensions. Especially surface structures with intersecting square grids with a linewidth near 40 m lead to good cell viability. Cells grown on a square pattern with a linewidth of 40 m show numerous pseudopodia which is an indication of cell adhesion. In contrast, rectangular patterns with only one dimension below 10 m do not favour cell adhesion.

Machining of Biocompatible Polymers with Shaped Femtosecond Laser Pulses.

Using a pulse shaper femtosecond laser pulses with variable length are applied in machining biocompatible polymers. It has been found that efficient material ablation can be achieved resulting in sharp cut edges. Systematic variation of the pulse length shows that the shortest pulses allow working with the lowest pulse energy.

Material processing with shaped femtosecond laser pulses

Laser material processing of aluminium and some polymers such as polyamide and low-density polyethylene has been performed using femtosecond pulses with different pulse durations. In order to investigate and optimize the ablation process we have developed an experimental setup with spatial light modulator for phase and amplitude modulation of the pulses. Considerable differences in the integrity of areas surrounding cut edges could be found for cuts of aluminum foil made by 70 fs and 230 fs laser ablation. For shorter pulses less damaged area caused by shock waves and less melting of the material have been observed. No debris was attached to the cut edges. The ablation of polymer surfaces has been carried out in nanoand femtosecond regimes. Strong heat transfer into the target, the consequent melting and even bubbling prevent a precise machining of polymers by nanosecond pulses. In addition femtosecond laser ablation allows creation of the holes on the polymer surface with higher precision. Such structures obtained in laser machining experiments can provide the opportunity for designing medical implants with high precision.