Matthias Gieseke

Poly-ε-caprolactone Coated and Functionalized Porous Titanium and Magnesium Implants for Enhancing Angiogenesis in Critically Sized Bone Defects.

For healing of critically sized bone defects, biocompatible and angiogenesis supporting implants are favorable. Murine osteoblasts showed equal proliferation behavior on the polymers poly-ε-caprolactone (PCL) and poly-(3-hydroxybutyrate)/poly-(4-hydroxybutyrate) (P(3HB)/P(4HB)). As vitality was significantly better for PCL, it was chosen as a suitable coating material for further experiments. Titanium implants with 600 µm pore size were evaluated and found to be a good implant material for bone, as primary osteoblasts showed a vitality and proliferation onto the implants comparable to well bottom (WB). Pure porous titanium implants and PCL coated porous titanium implants were compared using Live Cell Imaging (LCI) with Green fluorescent protein (GFP)-osteoblasts. Cell count and cell covered area did not differ between the implants after seven days. To improve ingrowth of blood vessels into porous implants, proangiogenic factors like Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were incorporated into PCL coated, porous titanium and magnesium implants. An angiogenesis assay was performed to establish an in vitro method for evaluating the impact of metallic implants on angiogenesis to reduce and refine animal experiments in future. Incorporated concentrations of proangiogenic factors were probably too low, as they did not lead to any effect. Magnesium implants did not yield evaluable results, as they led to pH increase and subsequent cell death.

SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.

Selective Laser Melting of Magnesium and Magnesium Alloys

Selective Laser Melting (SLM) offers the possibility to create three dimensional parts by having full freedom of design. Therefore prototypes can be produced faster and conventionally manufactured parts can be shaped individually, including an optimized design regarding potential loads and parts weight. The manufacturing of biocompatible metals like 316L and TiA16V4 is already industrially established. Because of the corrosive and mechanical properties of magnesium and the advantages of the SLM process, using magnesium is of great interest for manufacturing individual biodegradable implants. Recent investigations on SLM of magnesium have not led to successful operation so far. Due to the low vaporizing temperature, manufacturing non-porous and three dimensional parts from magnesium was not possible yet. Following a new strategy, using an industrial SLM system with an overpressure building chamber, investigations on SLM of magnesium are now carried out in order to overcome these difficulties and produce fully dense three dimensional parts.

Comparison of Selective Laser Melted Titanium and Magnesium Implants Coated with PCL

Degradable implant material for bone remodeling that corresponds to the physiological stability of bone has still not been developed. Promising degradable materials with good mechanical properties are magnesium and magnesium alloys. However, excessive gas production due to corrosion can lower the biocompatibility. In the present study we used the polymer coating polycaprolactone (PCL), intended to lower the corrosion rate of magnesium. Additionally, improvement of implant geometry can increase bone remodeling. Porous structures are known to support vessel ingrowth and thus increase osseointegration. With the selective laser melting (SLM) process, defined open porous structures can be created. Recently, highly reactive magnesium has also been processed by SLM. We performed studies with a flat magnesium layer and with porous magnesium implants coated with polymers. The SLM produced magnesium was compared with the titanium alloy TiAl6V4, as titanium is already established for the SLM-process. For testing the biocompatibility, we used primary murine osteoblasts. Results showed a reduced corrosion rate and good biocompatibility of the SLM produced magnesium with PCL coating.

Additive manufacturing in micro scale

Additive manufacturing is getting increasingly attractive for industrial production of unique or small series parts. Although spatial resolution and surface quality have been improved within the recent years, there is a request for further development to achieve ready to use surfaces or to realize important details. Using selective laser micro melting (SLµM) can be the first step to adapt these requirements to small size components.

Simulation von Selective Laser Melting Prozessen

Selective Laser Melting (SLM) ist ein additives Fertigungsverfahren, bei dem ein Metallpulverbett punktuell aufgeschmolzen wird. So konnen komplexe Geometrien hergestellt werden. Allerdings sind die vielfaltigen, miteinander interagierenden physikalischen Prozesse nicht vollstandig verstanden. In der Prozess-, Material- und Bauteilentwicklung sind daher zeit- und kostenintensive Experimente notig. Die Entwicklung innovativer Simulationsverfahren aus dem Bereich der computergestutzten Ingenieurswissenschaften bietet das Potential, den Einfluss der Prozessparameter auf die Bauteileigenschaften vorherzusagen. Eine genaue Vorhersage bietet die Moglichkeit einer individualisierten Prozessplanung, sodass Bauteileigenschaften nach Bedarf lokal angepasst werden konnen.

Entwicklungstrends zum Einsatz des selektiven Laserstrahlschmelzens in Industrie und Biomedizintechnik

Beim selektiven Laserstrahlschmelzen werden metallische Pulverwerkstoffe schichtweise aufgetragen, selektiv mittels Laser verschmolzen und somit vollstandig dichte Bauteile erzeugt. Es werden ahnliche Eigenschaften wie bei konventionell verarbeiteten Werkstoffen erzielt, sodass diese Verfahren fur die Produktion von Prototypen oder zur Fertigung von Endprodukten eingesetzt werden. Zudem gibt es eine Vielzahl verwendbarer Werkstoffe, um die jeweils erwunschten Bauteileigenschaften umzusetzen. Viele Werkstoffe, wie Titanlegierungen fur Leichtbauteile im Bereich der Luftfahrt oder Kobalt-Chrom zur Umsetzung patientenspezifischer Zahnimplantate, sind bereits industriell fur das SLM®-Verfahren etabliert.