Plant-Derived Polynucleotides/Polydeoxyribonucleotides in Skin Biomaterials: Delivery Platforms and Bioactivity Attribution

In the fields of dermatology and skin biomaterials, polynucleotides (PN) and polydeoxyribonucleotides (PDRN) typically refer to deoxyribonucleic acid (DNA)-based polymers or heterogeneous DNA-fragment mixtures rather than ribonucleic acid (RNA) polynucleotides. Recently, plant-derived PN/PDRN preparations, sourced from callus, adventitious roots, and plant cell culture systems, have emerged as a promising animal-free material class. However, current evidence remains predominantly preclinical and should not be construed as demonstrating clinical equivalence to conventional animal-derived PDRN. This review synthesizes recent reports on plant-derived and other non-animal PN/PDRN and integrates them with delivery platform evidence relevant to skin biomaterials. We distinguish directly demonstrated findings from plant-derived preparations from inferences drawn from animal-derived PDRN, synthetic sequence-defined nucleic acids, or broader biomaterial delivery literature. The review further emphasizes operational molecular definitions, polymer length and fragment distribution reporting, DNA purity and integrity, RNA carryover, residual nucleoproteins and plant-derived macromolecules, free nucleotide/nucleoside or degradation product fractions, enzymatic degradation, delivery matrices, and hypothesis-matched controls. Available data suggest overlapping biological signatures with classical PDRN, including keratinocyte repair, fibroblast extracellular matrix (ECM) remodeling, and A2A receptor-associated readouts; however, A2A receptor dependency has not been directly established for most plant-derived PN/PDRN preparations and should be interpreted as a working mechanistic hypothesis unless perturbation experiments demonstrate pathway dependence. Direct head-to-head studies using matched DNA dose, molecular weight distribution, purity, delivery platform, and exposure conditions remain limited. Accordingly, plant-derived PN/PDRN should be evaluated as a source–process–structure–platform–function system rather than as a DNA fraction alone.