Regional Cellular Reprogramming via a Non‐Coding RNA Engineered Electrospun Fibrous Patch

Abstract Reprogramming of scar cell lineages within the injury region is expected for tissue regeneration. However, the programming elements to achieve targeted enrichment of specific cell lineages and intracellular genetic editing in the regions remains challenging. Here, a long non‐coding genetic reprogramming electrospun patch (Lnc‐GEP) by remodeling poly (lactic‐co‐glycolic acid) electrospun fibers with the reprogramming element regulatin lnc‐H19 identified in the non‐coding transcriptional profile of tendon adhesion tissue is reported. Through intracellular genetic programming element encapsulated in nanogels, lnc‐GEP achieved 92.74% activity retention with indiscriminate transfection efficiency for effective remodeling of non‐coding genetic material. In particular, lnc‐GEP reduced the activation level of Smad3 phosphorylation by 73.52% and extracellular matrix secretion of myofibroblasts by, demonstrating the targeting reprogramming of mesenchymal cell phenotype. In mouse tendon injury, lnc‐GEP downregulated tendon adhesion score by 3 grades and alleviated adhesion fibrosis from 78.41% to 32.63%, thus achieving endogenous healing from mechanical strength, ultrastructure, and gait function levels instead of adhesion scars. In conclusion, non‐coding genetic remodeling electrospun patches via regional cellular reprogramming are applied to show scar‐related cell lineage resetting in a targeted manner without interfering with the regenerative process, providing a new avenue for the prevention and treatment strategy of tissue adhesions.