The SynMech project is developing a mechanogenetic technology to regulate functional connectivity of neural circuits for therapeutic purposes in brain disorders. The objective of SynMech-Hop on is to complement the original work plan with i) novel, highly translational human 2D and 3D in vitro models of epileptic seizures, ii) increase the human translational value and reduce animal use (3Rs), and iii) enhance the project innovation capacity via higher TRL levels towards clinical applicability, business development, regulatory, societal acceptance and industrial key stakeholder communications. Our ambition is to use in vitro neural models derived from human induced pluripotent stem cells (hiPSCs) to evaluate biosafety and efficacy for epilepsy of synaptic mechanogenetics. BIOT provides a wide variety of human in vitro methodologies, which could complement the excellence of SynMech technologies by generating standardized in vitro human epilepsy models with the use of patient-derived iPSCs and epileptic seizure-inducing drugs, and thus fill current scientific gaps. Induced seizures can be used to effectively address human in vitro seizure-liability testing because they allow us to define both electrogenic and non-electrogenic aspects of epilepsy in a spatiotemporal fashion, enabling the assessment of the efficacy and biocompatibility of SynMech technology components (functionalized biocompatible magnetic nanoparticles, bioengineered synaptic mechanosensors and magnetic stimulators). We will assess efficacy and safety of synaptic mechanogenetics as an antiepileptic treatment in human 2D and 3D in vitro models, comparing it to established pharmacological anticonvulsant approaches. This will allow SynMech partners to add an additional layer of interdisciplinarity and integrate BIOT’s in vitro solutions to replace some animal experiments (3Rs) and to enhance industrial and medical translatability, underpinning SynMech’s innovations towards higher TRLs.