Nanocarriers for Mrna and Protein Delivery: Innovative Tools and Strategies in Tendon Repair

The integration of nanocarriers for the co-delivery of mRNA and/or proteins represents a novel and cutting-edge approach in tendon repair, combining precision molecular therapies with advanced biomaterial science. By enabling the concurrent delivery of genetic and protein-based therapeutic agents, these systems offer a dual-action strategy: mRNA delivery facilitates transient expression of therapeutic proteins directly within target cells, while protein delivery ensures immediate bioactivity to stimulate and enhance repair processes. Among various nanocarrier systems, bio-hybrid lipid nanoparticles, such as lipid-protein conjugates, have emerged as promising platforms due to their superior biocompatibility, controlled release profiles, and capacity for targeted delivery. However, challenges related to stability, immune response mitigation, and efficient intracellular delivery remain areas of active investigation. In this context, biomimetic ProteoLipid NanoCarriers (PL-NCs) offer significant advantages for tendon repair applications. PL-NCs are designed to mimic natural cellular components, enhancing their interaction with biological membranes and facilitating endosomal escape for improved cytoplasmic delivery of their cargo. Furthermore, the dual capability of PL-NCs to co-deliver mRNA and/or proteins in a controlled and sustained manner leverages synergistic biological effects, potentially accelerating tendon regeneration and functional recovery. The objective of the present work is to explore the therapeutic potential of PL-NCs for tendon repair by optimizing their delivery of collagen Type I codifing mRNA or Tenomodulin protein to revers the impaired biochemistry of human Tendon Progenitor Stem Cells (1–3) collected from pathological tendon surgery explants (RB n. 151, 29.10.2020). This research underscores the promise of biomimetic nanocarrier-based co-delivery systems in regenerative medicine, particularly in musculoskeletal applications, and provides a foundation for future clinical translation.