Hemocompatibility of Nanotitania-Nanocellulose Hybrid Materials

Abstract

In order to develop a new type of improved wound dressing, we combined the wound healing properties of nanotitania with the advantageous dressing properties of nanocellulose to create three different hybrid materials. The hemocompatibility of the synthesized hybrid materials was evaluated in an in vitro human whole blood model. To our knowledge, this is the first study of the molecular interaction between hybrid nanotitania and blood proteins. Two of the hybrid materials prepared with 3 nm colloidal titania and 10 nm hydrothermally synthesized titania induced strong coagulation and platelet activation but negligible complement activation. Hence, they have great potential as a new dressing for promoting wound healing. Unlike the other two, the third hybrid material using molecular ammonium oxo-lactato titanate as a titania source inhibited platelet consumption, TAT generation, and complement activation, apparently via lowered pH at the surface interface. It is therefore suitable for applications where a passivating surface is desired, such as drug delivery systems and extracorporeal circuits. This opens the possibility for a tailored blood response through the surface functionalization of titania.

Keywords: coagulation; complement system; contact system; nanocellulose; platelets; titania.

Figure A1

Incubation chamber with two wells (a), rubber tightening (b), and lid (c). Toluidine blue was applied on the surface to confirm successful heparinization. The toluidine blue dye binds to heparin causing purple-blue staining (indicated by the white arrow) resistant to removal upon washing with water.

Figure A2

Blood chambers after incubation for the control and the four different materials. The white arrows indicate blood clots.

Figure 1

Photographs of the newly synthesized materials. Bright areas are light reflections. (a) CNF_PEG, (b) CNF_PEG_TiO₂, (c) CNF_PEG_Captigel, and (d) CNF_PEG_TiBALDH. Scale bars indicate 4 cm.

Figure 2

SEM micrographs of the control material, (a) CNF_PEG, and the three hybrid materials (b) CNF_PEG_TiO₂, (c) CNF_PEG_Captigel, and (d) CNF_PEG_TiBALDH. The inserted EDX spectra beneath the micrographs confirm the presence of titanium in materials (b–d). The scale bars indicate 10 μm.

Figure 3

Assessment of coagulation activation induced by the test surfaces (CNF_PEG_TiO₂, CNF_PEG_Captigel, and CNF_PEG_TiBALDH, abbreviated to TiO₂, Captigel, and TiBALDH, respectively, in the figure) and the controls (CHS and CNF_PEG) compared to the initial samples after incubation in human whole blood. (a) Remaining platelets (n = 5), (b) generation of TAT-complexes (n = 5). (c) Formation of FXIa–C1INH complexes (n = 3) and (d) of FXIIa–C1INH complexes (n = 3). Data are presented as mean ± SEM. The data in (a) were normalized against the initial values for each donor. * Significant at p < 0.05 level, ** significant at p < 0.01 level, *** significant at p < 0.001 level.

Figure 4

Generation of complement activation products after incubation of the test surfaces, (CNF_PEG_TiO₂, CNF_PEG_Captigel, and CNF_PEG_TiBALDH, abbreviated to TiO₂, Captigel, and TiBALDH, respectively, in the figure) and the controls (CHS and CNF_PEG) compared to the initial samples after incubation in human whole blood. (a) Relative concentration of C3a (n = 3). (b) Relative concentrations of sC5b-9 (n = 3). Data are presented as mean ± SEM. Significant differences (p < 0.05) are indicated by *. The data in (a,b) were normalized against the initial value of each donor.