Computational analysis of collagen delivery to the striatum

Introduction In recent years, cell therapy has emerged as a promising therapeutic strategy for Parkinson’s disease. To increase cell viability, biomaterials are used to facilitate cell deposition, through injection, to the site of interest. However, the existing cell delivery approaches have shown limited success in clinical translation 1 .This study aims to develop a device for the delivery of a cell-embedded in situ forming hydrogel. Here, computational approaches on the delivery of collagen to the striatum are presented, to gain insight into different parameters affecting the delivery. Methods The delivery of collagen to the striatum was modelled computationally in the two-dimensional space. The striatum was modelled as a circular space, with an area of 3.98 cm2 corresponding to the mean volume of putamen in Parkinson’s disease patients2 . Within the finite volume method framework, the flow of collagen was considered incompressible, with non-Newtonian fluid behavior characterized experimentally, and constant inlet velocity corresponding to a maximum delivery volume. Results The effects of collagen injection on the velocity and pressure fields within the striatum were examined. Velocity streamlines and wall shear stress (WSS) values were also analysed near the edges of the needle, at the entrance of the collagen to the striatum. High WSS values may influence cell viability on the site of delivery. Conclusion Intrastriatal injection of a cell embedded hydrogel is a complex process which is not yet well characterized. Computational analysis of the delivery can assist to identify the obstacles facing clinical translation. Further analysis is required including 3D reconstruction from MRI images and computational modelling in the three-dimensional space

Flow simulation of a natural polymer in a syringe-needle delivery device

Neurodegenerative diseases, such as Parkinson's disease, affect a large num- ber of the erderly population and still remain untreated. In recent years, cell therapy has emerged as a promising therapeutic strategy. To increase cell viability, biomaterials are of- ten used as scaffolds and facilitate cell deposition, through injection, to the site of interest. However, fluid forces acting on the cells during injection may lead to their disruption or death. This study aims to develop a novel device for the delivery of a cell-embedded, in situ forming, collagen hydrogel. A preliminary simulation study on constricted channels rep- resenting the syringe was performed to gain insight into the effect of needle diameter and syringe geometry. Straight needles emanating co-axially from syringes of various geome- tries were computationally modelled in the two-dimensional space, using OpenFOAMⓇ. The natural collagen solution was modelled as a continuum medium, without cells, and the flow was assumed incompressible, with non-Newtonian fluid constitutive behaviour. The effects of needle diameter and syringe geometry on velocity and shear stresses were examined. The results highlight the importance of geometric characteristics on the design of new cell delivery devices. If cells pass from the syringe barrel to the needle, the pressure drop and the increased velocity could damage them. This is more likely to occur using higher Gauge needles. Further analysis is required including simulations of cells during injection and analysis of their deformation