A recent review published in Engineering explores the construction and potential applications of spinal cord and peripheral nerve organoids for regenerative medicine in neurotrauma. The article, titled “Engineering Spinal Cord and Peripheral Nerve Organoids: Strategies for Construction and Potential Applications for Regenerative Medicine in Neurotrauma,” provides a comprehensive overview of the latest advancements in organoid technology and its implications for treating spinal cord injury (SCI) and peripheral nerve injury (PNI).

Organoids are three-dimensional cell clusters derived from stem cells that can self-renew and self-organize, mimicking the structure and function of real organs. These miniaturized organ models have gained significant attention in the field of regenerative medicine due to their potential to revolutionize the treatment of neurotrauma. According to the review, “Organoids have emerged as powerful tools for disease modeling, mechanistic exploration, drug screening, and regenerative medicine.” They offer a unique opportunity to study the complex cellular interactions and tissue structures involved in SCI and PNI.

The review delves into the genesis and structure of the spinal cord and peripheral nervous system, highlighting the importance of accurately replicating the cellular components and structures of these organs. It discusses the key factors for constructing spinal cord and peripheral nerve organoids, including cellular origin, signaling-modulating factors, and matrix materials for 3D culture. The authors emphasize that the choice of starting cells, such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), significantly impacts the organoids' activity and response to morphogens.

Signaling pathways, including TGF-β, BMP, WNT, FGF, and SHH, play a crucial role in the formation and development of organoids. By regulating these pathways with specific inducers and cytokines, researchers can generate organoids with distinct characteristics. For instance, spinal cord organoids can be induced to exhibit ventral-dorsal features, while dorsal root ganglion (DRG) organoids can be generated through targeted induction.

The review also highlights the importance of matrix materials in 3D culture, which provide essential nutrients, adhesion sites, and biophysical cues for cell differentiation. While Matrigel is commonly used, its inconsistencies and potential immunogenicity have led researchers to explore alternative materials such as decellularized extracellular matrix (dECM) and synthetic hydrogels.

In addition to the construction strategies, the review explores the potential applications of spinal cord and peripheral nerve organoids in neurotrauma. These include cell therapy, tissue engineering, and the use of organoid-derived extracellular vesicles (EVs) for promoting neural repair. The authors note that “Organoid transplantation is a promising regenerative medicine therapy for SCI and PNI because organoids contain complex cell types and can respond to post-transplantation niches for differentiation and maturation.”

Despite the promising advancements, the review acknowledges several challenges in the field. These include the high heterogeneity among neural organoids, incomplete replication of organ functions, and limitations in vascularization and immune microenvironment construction. Future research will need to address these challenges to fully realize the potential of organoids in regenerative medicine.

The review in Engineering underscores the significant potential of spinal cord and peripheral nerve organoids in neurotrauma regenerative medicine. By leveraging advancements in organoid technology, researchers and clinicians may be able to develop more effective treatments for SCI and PNI, ultimately improving patient outcomes.

The paper “Engineering Spinal Cord and Peripheral Nerve Organoids: Strategies for Construction and Potential Applications for Regenerative Medicine in Neurotrauma,” is authored by Jiaqi Su, Zhiwen Yan, Xiaoxuan Tang, Tong Wu, Jue Ling, Yun Qian. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.05.011. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.