465775 Gelation Process of in Situ Crosslinkable Hydrogels in the Static Mixer

Monday, November 14, 2016
Market Street (Parc 55 San Francisco)
Takuro Hozumi1, Seiichi Ohta2 and Taichi Ito2, (1)Department of Chemical System Engineering, the University of Tokyo, Tokyo, Japan, (2)Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo, Japan

Static mixers have been widely used in industry to mix various kinds of fluids and are recently utilized to fabricate hydrogels. Hydrogels have attracted much attention in the biomedical field as tissue adhesions, drug carriers or tissue engineering scaffolds. It was reported that the fast gelation rate made hydrogel inhomogeneous, which resulted in the decrease of mechanical strength. However, few studies have been done on the effect of mixing on the gelation process.

In the present study, we studied the gelation process of in situ crosslinkable hydrogels, which can be formed simply by mixing two reactive solutions, in a Kenics static mixer. In situ crosslinkable hydrogels are promising material for biomedical application, because they can be administered into any desired location in the body without large incision. The effects of process parameters, e.g., flow rate, the number of mixing elements, and the concentration of the pre-gel polymer solution, on the pressure drop during mixing and the homogeneity of formed hydrogels were investigated.

We used the static mixers with 4, 8, 12, 16 elements. Green dye was used as a tracer to visualize the flow inside the static mixer. To organize the results, we calculated Damköhler number (Da), a dimensionless number expressed as the ratio of the residence time in the static mixer to the batch gelation time. The pressure drop between the inlet and outlet of the static mixer was measured in fabricating in situ crosslinkable hydrogels. The flow rate was controlled using a syringe pump. As an indicator of homogeneity, we observed the formed hydrogels via confocal microscopy and calculated coefficient of variance (COV) by dividing the standard deviation by the average of the obtained pixel values of confocal images (N=3).

As a model material for ionically crosslinkable hydrogels, calcium alginate was utilized in this study. Alginate is a natural polysaccharide comprising repeating units of alpha-L-guluronate and beta-D mannuronate. When mixed with calcium ions, alginates are crosslinked with calcium ions via the so-calledgegg box modelh, producing an insoluble hydrogel. Without calcium ions, the fluid was sol and the stream line got thinner along with elements in the static mixer. On the other hand, in the presence of enough amount of calcium ions, hydrogels formed in the mixer interrupted the flow, resulting in green stagnations. The pressure drop increased with the number of elements for both with and without calcium ions, but it showed different tendency against the axial velocity because the mixing efficiency differed. These results were organized by using Da. The normalized pressure drop, normalized by that in 0 mM calcium ions case in the same operation condition, increased monotonically with Da until Da was 10. COVs of the hydrogels showed similar tendency, first increased and then decreased with increasing Da. When Da was low, gelation occurs after the extrusion rather than inside the static mixer. With higher Da, the hydrogels were more likely to be formed inside the static mixer, resulting in the increased pressure drop and decreased homogeneity of formed hydrogel. When Da is further increased, hydrogel was not completely formed inside the static mixer due to insufficient mixing at very low axial velocity, leading to the increase in the homogeneity (T. Hozumi, S. Ohta and T. Ito, Ind. Eng. Chem. Res., 2015, 54, 2099-2107).

In addition to ionic crosslinking, various kinds of crosslinking reactions can be utilized for producing in situ crosslinkable hydrogels. It has been reported that the types of crosslinking reaction significantly affect the gelation rate and property of in situ crosslinkable hydrogels. In this study, the above experimental examination was also applied for other types of crosslinking reaction, such as Schiff base formation and Michael addition. The difference in the gelation process in the static mixer and consequent property of formed hydrogels will be discussed.


Extended Abstract: File Not Uploaded
See more of this Session: Poster Session: Fluid Mechanics (Area 1J)
See more of this Group/Topical: Engineering Sciences and Fundamentals