Localizing Strain in a 2D in vitro Stretch System to Model Regional Injury Dynamics

Traumatic brain injury (TBI) is a disruption in normal brain function caused by mechanical insult to the head. Nonuniform brain tissue deformation complicates TBI diagnosis and treatment. Capturing this spatial heterogeneity in vitro is important for studying region-specific injury responses under controlled conditions. This work presents the development and validation of a two-dimensional (2D) in vitro stretch injury model that produces bimodal strain within a single culture well, creating coexisting populations of injured and uninjured cells. The previously established system uses a flexible polydimethylsiloxane (PDMS) membrane indented by a rigid post to deliver a controllable, clinically relevant stretch to 2D cultures. To induce strain heterogeneity, the system was modified to increase friction at the membrane–post interface, reducing strain in the center of a well, and redistributing deformation to the periphery. Experimental strain measurement confirmed that central strain is reduced under high-friction conditions compared to low-friction. However, experimental measurement of peripheral strain was not feasible due to out of plane deformation of the periphery. A finite element analysis (FEA) was developed to address this limitation, incorporating membrane thickness and hyperelastic behavior. The FEA model, validated against experimental data, accurately predicted strain distributions and identified an indentation depth that produced the desired bimodal strain pattern— a protected center, and injurious periphery. Human induced pluripotent stem cell (hiPSC)-derived astrocytes were cultured on polydopamine and Matrigel® coated PDMS membranes and subjected to the high-friction indentation. Calcein AM staining before and after injury revealed decreased cell viability in the periphery, and maintained viability in the center, consistent with predicted strain fields. This study demonstrates, for the first time, a 2D in vitro stretch model generating spatially heterogeneous strain and biological responses within a single well. This work advances TBI modeling, demonstrates a novel method for culturing hiPSC-derived astrocytes on PDMS, and expands opportunities for mechanobiological studies of neural cell injury and repair.

Author dc:creator

• Angela Mitevska (23292166)

• Engineering
• Biomedical

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451929.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451929