Dynamic Nano–Bio Interfaces in Regenerative Medicine: From Molecular Interactions to Tissue-Specific Regeneration

Abstract

Nanomaterials have emerged as versatile platforms for modulating biological processes and creating advanced interfaces for tissue regeneration. However, their biological behavior is not determined solely by their intrinsic physicochemical properties but evolves dynamically following interaction with the biological environment. This review provides a comprehensive perspective on nano–bio interfaces, emphasizing the mechanisms through which nanomaterials interact with proteins, cellular membranes, intracellular compartments, immune cells, stem cells, and tissue microenvironments. Particular attention is given to the formation and evolution of the protein corona, cellular recognition and uptake, intracellular trafficking, oxidative and inflammatory responses, and interactions with the immune system. The influence of nanomaterial-mediated signals on stem-cell adhesion, proliferation, migration, mechanotransduction, metabolism, and lineage-specific differentiation is further discussed. Tissue-specific applications in bone, cartilage, neural, cardiac, vascular, and skin regeneration are examined to highlight how nanomaterial properties can be adapted to distinct biological and mechanical environments. In addition, the review addresses nanomaterial degradation, persistence, long-term biocompatibility, nanotoxicity, reproducibility, and challenges associated with clinical translation. Emerging strategies involving three-dimensional models, organ-on-chip platforms, single-cell and spatial omics, artificial intelligence, and adaptive nanomaterials are also considered. Overall, this review emphasizes a shift from designing nanomaterials solely for structural support or passive biocompatibility toward the development of dynamic, biologically instructive, and tissue-specific nano–bio interfaces capable of actively regulating cellular and immune responses. Such a mechanistic and predictive approach may facilitate the development of safer and more effective nanomaterials for next-generation regenerative medicine.