Forecasting Approach to Investigate Dynamic Growth of Organoid within 3D Matrix for Distinct Perspective

Abstract

Organoid as a 3D structured model in vitro has difficulty in controlling its size. This issue becomes problematic when it is applied in a microfluidic source and sink-based because different dimension leads to different exposure to morphogen resulting in different cell fate. As a model used for biomedical purposes, this problem could lead to a discrepancy. This research is imposed to implement the forecasting method to study the dynamic of organoid growth profile. This approach could help a better understanding via spatiotemporal perspective complemented with a mathematical formula. The forecasting approach that clarifies the trend of this organoid growth by assessing whether the decided trend fits in every (or particular) stage (or not) has not been informed yet. Neural tube organoids have four different mechanical stiffness (0,5 kPa, 2 kPa, 4 kPa, 8kPa) which are documented in three days by time-lapse microscopy used in this experiment. These objects are mapped in a spatiotemporal fashion investigated in the profile and assessed by exponential trend. The actual phenomenon and forecasted result are evaluated by Mean Absolute Percentage Error (MAPE). Based on the result, the profile of organoid growth indicates that the organoid develops mostly following an exponential profile with the highest R2 value of 0,9868 and the lowest being 0,8734. Based on the MAPE value calculation it could be confirmed that the MAPE value on day 3 is the highest among the others indicating that the extended time of growth tends to have a different profile rather than the exponential trend after day 2. It should be noted that on the lowest stiffness (0,5 kPa) the mechanical properties do not significantly affect the organoid size during the development. Almost all (11 by 12 data or 91,6%) of the MAPE value is in excellent criteria (the value is less than 10%). Only one data does not belong to that classification which is in 8 kPa on day 3. Indicating that the higher stiffness the stronger effect on the system. From the axis development perspective, the organoid does not follow any specific pattern. This research could be a reference for a better understanding of the organoid growth profile in the 3D matrix environment which is nowadays become a hot topic in biomedical applications.