Title: Harnessing Bioscaffold-Coupled Stimulation Through Electroactive Graphene Foam for Enhanced Cellular and Mechanical Responses: Applications in Cartilage Tissue Engineering

Program: Biomedical Engineering PhD

Committee Chair: David Estrada

Committee: David Estrada, Eric Hayden, Sophia Theodossiou, John Oakey

Abstract: Osteoarthritis is a leading cause of joint degeneration, with limited treatment options that
fail to restore native cartilage. Tissue engineering offers a promising strategy by
combining cells, scaffolds, and bioactive cues to regenerate functional tissue, though
challenges remain in developing systems that integrate and precisely control these signals
in three-dimensional environments. This work establishes a scaffold-coupled electrical
stimulation (ES) platform using electroactive graphene foam (GF) to modulate cellular
and mechanical responses relevant to cartilage tissue engineering. Custom
stereolithography-printed bioreactors were developed to deliver low-voltage biphasic
square waves (20–60 mVpp, 1 kHz) directly to GF scaffolds under submerged culture,
maintaining waveform fidelity and cytocompatibility (>90% viability). ATDC5
chondroprogenitor cells exhibited strong attachment and infiltration within the opaque 3D
scaffold, visualized using a correlative imaging workflow combining fluorescence, SEM,
and X-ray micro-CT. ES induced up to a 230% increase in calcium fluorescence
intensity, and proteomic analysis revealed voltage-dependent shifts in ECM, cytoskeletal,
and signaling protein expression. These molecular differences coincided with enhanced
mechanical performance, with stimulated composites showing up to a ~25% increase in
equilibrium modulus and 65.6% greater energy dissipation under cyclic compression at
60 mVpp. This integrated system offers a tunable platform for delivering and studying
direct ES in vitro and provides new insights into the mechanistic effects of electrical cues
on chondroprogenitor behavior.