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Abstract Purpose of Review This concise review delves into the pivotal role of three-dimensional (3D) nanostructured scaffolds in fostering mesenchymal stromal cells (MSC) immunomodulatory capabilities, with a specific focus on orthopedic applications. In this ever-advancing research field, where inflammation and tissue repair are intricately linked, manipulation of the immunomodulatory properties of MSCs becomes crucial, especially for inflammatory-based diseases such as osteoarthritis (OA). The primary inquiries include the promise of nanoscale tools to revolutionize orthopedic regenerative medicine, the role of tailored design features in steering cellular immunomodulatory response, and the resulting beneficial impact on tissue regeneration. Recent Findings Recent studies demonstrate the crucial importance of precise control over 3D scaffold design at the nanoscale to maximize the efficacy of regenerative therapies. Compared to 2D, engineered 3D environments with specific chemical composition and finely tuned physical nano-features, heighten MSC secretion of immunosuppressive factors including transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PGE2), indoleamine-pyrrole 2,3-dioxygenase (IDO), and interleukin-10 (IL-10), contributing to improve cartilage and osteo differentiation. Summary Nanostructured 3D scaffolds characterized by nano topography, roughness, high porosity, biomimetic stiffness and chemistry, offer a sophisticated means to optimize the immunosuppressive potential of MSCs by allowing the spatiotemporal control over signaling molecules at the nanoscale. Polymeric constructs, notably collagen-based ones, lead to heightened immunomodulatory response and superior cellular differentiation. This effect is because 3D constructs provide a biomimetic environment that enhances cell interaction, controls cell behavior, and modulates the secretion of anti-inflammatory cytokines. The integration of innovative 3D nanostructured approaches into MSC culture systems paves the way for significant strides in cell therapy, addressing current challenges in their clinical application and holding great promise for developing more effective and precise treatments for orthopedic inflammatory disorders.
Banche‐Niclot et al. (Sat,) studied this question.