Fabrication of three-dimensional hydrogel scaffolds for modeling shunt failure by tissue obstruction in hydrocephalus

Fabrication of three-dimensional hydrogel scaffolds for modeling shunt failure by tissue obstruction in hydrocephalus

Fluids and Barriers of the CNS, November 2015

26578355

Carolyn Harris, Kelsie Pearson, Kristen Hadley, Shanshan Zhu, Samuel Browd, Brian W. Hanak, William Shain

Shunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively. Several mechanisms may be responsible, one of which involves shunt infiltration by reactive cells from the brain parenchyma. This has not been modeled in culture and cannot be consistently examined in vivo without a large sample size. We have developed and tested a three-dimensional in vitro model of astrocyte migration and proliferation around clinical grade ventricular catheters and into catheter holes that mimics the development of cellular outgrowth from the parenchyma that may contribute to shunt obstruction. Cell attachment and growth was observed on shunt catheters for as long as 80 days with at least 77 % viability until 51 days. The model can be used to study cellular attachment to ventricular catheters under both static and pulsatile flow conditions, which better mimic physiological cerebrospinal fluid dynamics and shunt system flow rates (0.25 mL/min, 100 pulses/min). Pulsatile flow through the ventricular catheter decreased cell attachment/growth by 63 % after 18 h. Under both conditions it was possible to observe cells accumulating around and in shunt catheter holes. Alone or in combination with previously-published culture models of shunt obstruction, this model serves as a relevant test bed to analyze mechanisms of shunt failure and to test catheter modifications that will prevent cell attachment and growth.