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.

Poly(3-caprolactone)s of controlled molecular weight and low molecular weight distribution were prepared via anionic ring-opening polymerization using a tetra-functional initiator. The prerequisite for crosslinking was achieved by end-capping of the arms with acrylate groups. Novel biodegradable polyester resins were prepared by crosslinking of the functional polyesters via Michael addition using amino-telechelic poly(tetrahydrofuran). Three-dimensional microstructuring via replica molding shows the potential of this material as substrate for biomedical devices. Thermal and mechanical properties were investigated to characterize the polyester resins, accelerated in vitro degradation studies were carried out in a Sørensen buffer at pH 7.4 and 60 C for up to 77 days. At different time intervals, the mass loss of the resins and the pH values of the buffer were determined, degradation products were investigated by means of NMR, SEC and ESI-MS and morphology of the degraded resins was checked via scanning electron microscopy. Compared to linear poly(3-caprolactone) the degradation rate of all resins is higher, showing a mass loss of 50% within 77 days.

Within this study, chemically modified polymer surfaces were to be developed, which should enhance the subsequent immobilization of various bioactive substances. To improve the hemocompatibility and endothelialization of poly(ε-caprolactone) (PCL) intended as scaffold material for bioartificial vessel prostheses, terminal amino groups via ammonia (NH₃) plasma, oxygen (O₂) plasma/aminopropyltriethoxysilane (APTES), and 4,4'-methylenebis(phenyl isocyanate) (MDI)/water were provided. Then, immobilization of the anti-inflammatory and antithrombogenic model drug acetylsalicylic acid (ASA) and vascular endothelial growth factor (VEGF) were performed by employing N,N-disuccinimidyl carbonate (DSC) as crosslinker. Contact angle and fluorescence measurements, X-ray photoelectron spectroscopy and infrared spectroscopy confirmed the surface modification. Here the highest functionalization was observed for the O₂ plasma/APTES modification. Furthermore, biocompatibility studies demonstrated that the surface reactions have no negative influence, neither on the viability of L929 mouse fibroblasts, nor on primary or secondary hemostasis. Release studies showed that the immobilization of ASA and VEGF on the modified PCL surface via DSC is greatly improved compared to the adsorption-only reference. The advantage of DSC is that it immobilizes both bioactive substances via non-hydrolyzable and/or hydrolyzable covalent bonding. The highest ASA loading and cumulative release was detected using NH₃ plasma-activated PCL samples. For VEGF, the O₂ plasma/APTES-modified PCL samples were most efficient with regard to loading and cumulative release. In conclusion, both modifications are promising methods to optimize PCL as scaffold material for bioartificial vessel prostheses.

Metallic biomaterials are widely used in maxillofacial surgery. While titanium is presumed to be the gold standard, magnesium-based implants are a current topic of interest and investigation due to their biocompatible, osteoconductive and degradable properties. This study investigates the effects of poly-ε-caprolactone-coated and previtalised magnesium implants on osteointegration within murine calvarial bone defects: After setting a 3 mm × 3 mm defect into the calvaria of 40 BALB/c mice the animals were treated with poly-ε-caprolactone-coated porous magnesium implants (without previtalisation or previtalised with either osteoblasts or adipose derived mesenchymal stem cells), porous Ti6Al4V implants or without any implant. To evaluate bone formation and implant degradation, micro-computertomographic scans were performed at day 0, 28, 56 and 84 after surgery. Additionally, histological thin sections were prepared and evaluated histomorphometrically. The outcomes revealed no significant differences within the differently treated groups regarding bone formation and the amount of osteoid. While the implant degradation resulted in implant shifting, both implant geometry and previtalisation appeared to have positive effects on vascularisation. Although adjustments in degradation behaviour and implant fixation are indicated, this study still considers magnesium as a promising alternative to titanium-based implants in maxillofacial surgery in future.

PurposeDrug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents.Materials and MethodsFive different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test.ResultsBoth endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces.ConclusionSurface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.