A HETEROGENOUS HYDROGEL BRAIN PHANTOM FOR CONVECTION-ENHANCED DRUG DELIVERY

Hydrogel plays an important role in several biomedical engineering applications, one being convection enhanced drug delivery (CED). During CED, a drug is locally injected into the brain to attack diseased or cancerous cells via infusion under pressure. Predicting the flow path of the injected drug during CED has been challenging because fluid infiltration through brain tissue will cause the solid to deform, causing a change in the resultant flow pattern. To characterize the pharmacodynamics of the injected drug through brain tissue, an accurate in vitro engineering model that emulates material properties of brain tissue is highly demanded. We thus propose to develop and characterize a heterogenous hydrogel structure to replicate the soft, porous, and complex structure of the organ, for further exploration of how injected fluid affects deformation which in turn affects the flow. In this study, we created and characterized a heterogeneous gel brain phantom consisting of hydrogel gel beads and matrix of different Young's moduli. Agar gel beads were fabricated from the gel solution (1 or 2 w/v%) using a rotating-liquid-based drop generator. With needles of two different inner diameters (0.413 and 1.372 mm), 1 w/ v% solution resulted in beads of a diameter of 1.17 mm and 1.47 mm, respectively, and 2 w/v% solution resulted in beads of a diameter of 1.70 mm and 1.99 mm, respectively. Through microscopic compression tests, the Young's moduli of agar beads were measured to be 34.2 kPa and 100.8 kPa for 1 and 2 w/v% cases, respectively. For validation, homogeneous agar discs were fabricated and tested: macroscopic Young's modulus values were 57.1 kPa and 143.2 kPa for 1 and 2 w/v%, respectively. The heterogeneous brain phantom was fabricated by embedding prepared agar gel beads into agar matrix of different concentrations (1% beads in 2% matrix and vice versa). Fabricated heterogeneous gel discs were characterized via compression tests, and the overall Young's modulus of the heterogenous phantom was found to be lower than that of the matrix. Discs made with 1% agar beads and 2% agar matrix resulted in a Young's modulus of 45.24 kPa, whereas discs made with 2% agar beads and 1% agar matrix resulted in a Young's modulus value of 18.95 kPa. Although simply binary, fabricated heterogenous agar discs demonstrate that their mechanical behavior differs from their homogeneous counterpart, which clearly supports urgent need for heterogenous gel phantom for advancing CED.