The National Institutes of Health (NIH) is offering exploratory/developmental research funding through the "Engineering Next-Generation Human Nervous System Microphysiological Systems" (MPS) R21 grant, which does not permit clinical trials. This grant invites early-stage and high-risk, high-reward projects that aim to advance the development of human cell-derived MPS models and related assays replicating complex nervous system architectures. The R21 mechanism targets projects lacking preliminary data but with high potential for significant impact. Researchers with preliminary data may consider applying to the related R01 funding opportunity (PAR-25-198).

This initiative is aimed at supporting MPS research in areas such as the aging process, aging-related diseases, and specific problems or needs associated with aging. Key research goals include the development of three-dimensional (3D) models using technologies like induced pluripotent stem cells to improve the study of normal and pathological nervous system development, function, and aging. Funded projects should advance current MPS technology by enabling analysis of complex nervous system functions, covering aspects like multi-lineage integration, maturation, and reproducible circuit-level activity. Projects should incorporate advancements such as novel substrates or synthesis technologies, defined cell types (e.g., neurons, astrocytes), innovative structural organization, or complex functional features for nervous system disease modeling.

Research can explore various innovative MPS approaches, including:
1. Using novel materials like 3D printing and bioreactors to enhance tissue maturation and organization.
2. Integrating specific cell types into functional units with physiologically relevant structures, such as vascularization or cerebrospinal fluid systems.
3. Developing strategies that improve metabolism, signaling, synaptic activity, and cellular connectivity.
4. Introducing single-cell analysis methods for better cell type differentiation within models.

Participating NIH institutes have specific focus areas within this initiative. For example, the National Institute on Mental Health (NIMH) encourages applications focusing on MPS models representing cognitive and affective brain functions, such as mood disorders and schizophrenia. The National Eye Institute (NEI) seeks MPS development that advances models of eye structures, while the National Institute on Alcohol Abuse and Alcoholism (NIAAA) focuses on MPS models that assess alcohol’s impact on neural circuits. Other institutes, such as the National Institute on Aging (NIA) and the National Institute on Deafness and Other Communication Disorders (NIDCD), have interests in MPS models for aging-related brain disorders (e.g., Alzheimer’s disease) and sensory functions, respectively.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, tribal entities, and foreign institutions. Registration with the System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code, Unique Entity Identifier (UEI), eRA Commons, and Grants.gov is required prior to application submission. Submissions must align with NIH policies on data management and sharing, with applicants encouraged to contribute data to the National Institute of Mental Health Data Archive (NDA) and follow strict guidelines for data quality, sharing, and confidentiality.

The award provides a combined direct cost budget of up to $275,000 over two years, with a maximum of $200,000 allowed in any one year. Applications are due by 5:00 PM local time on dates listed in the funding announcement, starting from February 16, 2025. Applicants should ensure compliance with submission guidelines, as incomplete or non-compliant applications may not be reviewed. Selected proposals will be reviewed for scientific and technical merit based on significance, innovation, rigor, and the project team’s expertise. Final funding decisions will consider peer review scores, available funds, and program priorities.

For additional information, applicants are encouraged to contact NIH program officers specific to each institute’s focus within the MPS initiative.