A hybrid 3D assembly method was developed to advance spheroid culture and enhance stem cell–based treatment of CNS injuries.

Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including disc herniation and spinal stenosis. While traditional growth factor therapies (e.g., TGFβ) are effective at transiently reversing degenerated disc by stimulation of matrix synthesis, it is increasingly accepted that bioscaffolds are required for sustained, complete IVD regeneration. Current scaffolds (e.g., metal/polymer composites, non-mammalian biopolymers) can be improved in one or more IVD regeneration demands: biodegradability, noninvasive injection, recapitulated healthy IVD biomechanics, predictable crosslinking, and matrix repair induction. To meet these demands, tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bio orthogonal hydro gel (BIOGEL). The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5–10 min, allowing a human operator to easily inject the therapeutic constructs into degenerated IVD. Moreover, BIOGEL encapsulation of TGFβ potentiated histological repair (e.g., tissue architecture and matrix synthesis) and functional recovery (e.g., high water retention by promoting the matrix synthesis and reduced pain) in an in vivo rat IVD degeneration/nucleotomy model. This BIOGEL procedure readily integrates into existing nucleotomy procedures, indicating that clinical adoption should proceed with minimal difficulty. Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules, our developed material platform can be extended to other payloads and degenerative injuries.

Stem cells show excellent potential in the field of tissue engineering and regenerative medicine based on their excellent capability to not only self-renew but also differentiate into a specialized cell type of interest. However, the lack of a non-destructive monitoring system makes it challenging to identify and characterize differentiated cells before their transplantation without compromising cell viability. Thus, the development of a non-destructive monitoring method for analyzing cell function is highly desired and can significantly benefit stem cell-based therapies. Recently, nanomaterial-based scaffolds (e.g., nanoarrays) have made possible considerable advances in controlling the differentiation of stem cells and characterization of the differentiation status sensitively in real time. This review provides a selective overview of the recent progress in the synthesis methods of nanoarrays and their applications in controlling stem cell fate and monitoring live cell functions electrochemically. We believe that the topics discussed in this review can provide brief and concise guidelines for the development of novel nanoarrays and promote the interest in live cell study applications. A method which can not only control but also monitor stem cell fate and function will be a promising technology that can accelerate stem cell therapies.