No abstract

We employed indirect rapid prototyping templating to fabricate bioactive and macroporous scaffolds for bone regeneration. This templating technique utilizes lost molds made of polycaprolactone by fused deposition modeling, in which the organic/ inorganic hybrid silica sol was filled and cured. Finally, the molds were dissolved and extracted, and the remaining macroporous hybrid glass constructs were recovered. The hybrid glass scaffolds offered a fully interconnected pore structure with 63-72% porosity measured by N2-pycnometry and Hg-intrusion. In bioactive sol-gel glasses one issue is the insufficient and inhomogeneous incorporation of calcium (II) ions. To address this problem we varied the curing conditions and tested the effect of the organic crosslinker on calcium retention. We strengthened the silica network by covalent crosslinking with trimethylolpropane ethoxylate which was functionalized with 3-(triethoxysilyl)propyl isocyanate. Those scaffolds showed compressive yield strengths of up to 12.7 MPa and compressive moduli between 18 and 288 MPa. Energy dispersive X-ray spectroscopy showed that a crosslinker content of 60% in the hybrids resulted in a homogeneous calcium distribution in the glass, in contrast to 40% where we found a layer of CaCl2 on the scaffold surface. The materials exhibited bioactivity in simulated body fluid which was monitored by scanning electron microscopy and X-ray powder diffraction.

In this study, we integrated different calcium sources into sol-gel hybrid glass scaffolds with the aim of producing implants with long-lasting calcium release while maintaining mechanical strength of the implant. Calcium(II)-release was used to introduce bioactivity to the material and eventually support implant integration into a bone tissue defect. Tetraethyl orthosilicate (TEOS) derived silica sols were cross-linked with an ethoxysilylated 4-armed macromer, pentaerythritol ethoxylate and processed into macroporous scaffolds with defined pore structure by indirect rapid prototyping. Triethyl phosphate (TEP) was shown to function as silica sol solvent. In a first approach, we investigated the integration of 1 to 10% CaCl2 in order to test the hypothesis that small CaCl2 amounts can be physically entrapped and slowly released from hybrid glass scaffolds. With 5 and 10% CaCl2 we observed an extensive burst release, whereas slightly improved release profiles were found for lower Calcium(II) contents. In contrast, introduction of melt-derived bioactive 45S5 glass microparticles (BG-MP) into the hybrid glass scaffolds as another Calcium(II) source led to an approximately linear release of Calcium(II) in Tris(hydroxymethyl)aminomethane (TRIS) buffer over 12 weeks. pH increase caused by BG-MP could be controlled by their amount integrated into the scaffolds. Compression strength remained unchanged compared to scaffolds without BG-MP. In cell culture medium as well as in simulated body fluid, we observed a rapid formation of a carbonated hydroxyapatite layer on BG-MP containing scaffolds. However, this mineral layer consumed the released Calcium(II) ions and prevented an additional increase in Calcium(II) concentration in the cell culture medium. Cell culture studies on the different scaffolds with osteoblast-like SaOS-2 cells as well as bone marrow derived mesenchymal stem cells (hMSC) did not show any advantages concerning osteogenic differentiation due to the integration of BG-MP into the scaffolds. Nonetheless, via the formation of a hydroxyapatite layer and the ability to control the pH increase, we speculate that implant integration in vivo and bone regeneration may benefit from this concept.