Table 2.

Therapeutic approaches for PNI: current status and standardization gaps

Therapy	Type	Key mechanism of action	Advantage	Limitation	Evidence level	Synergy w/ES	Synergy w/PRP	References
Primary Neurorrhaphy	Surgical	Direct end-to-end suture	Tension-free repair	Limited to clean injuries	Clinical standard	Not studied	Not studied	Dahlin (2008)
Nerve Autograft	Surgical	Biological scaffold	Gold standard for gaps	Donor site morbidity	Clinical standard	Enhanced axon growth	Not studied	Grujicić et al. (2003)
TENS	Electrical	Non-invasive neuromodulation	Easy application	Parameter-dependent	Preclinical/Clinical	N/A (is ES)	Potential	Alarcón et al. (2022)
NMES	Electrical	Muscle contraction guidance	Prevents atrophy	Requires optimization	Preclinical/Clinical	N/A (is ES)	Potential	Petriv et al. (2023)
Direct Current Stimulation	Electrical	Directional axon guidance	Cathodal targeting	Safety concerns	Preclinical	N/A (is ES)	Potential	Shen and Zhu (1995)
PRP	Biological	Multi-growth factor release	Autologous, anti-inflammatory	Composition variability	Preclinical/Clinical	High	N/A (is PRP)	Yadav et al. (2022)
Fibrin Glue	Adjunct	Limits scar formation	Reduces fibrosis	Adjunctive only	Preclinical	Not studied	Compatible	Mayrhofer-Schmid et al. (2024)
Conductive Hydrogels	Biomaterial	Scaffold + electrical cues	Combined physical/electrical support	Manufacturing complexity	Preclinical	High	High	Gao et al. (2024)
Gene Therapy (VEGF + G-CSF)	Biological	Dual factor delivery	Synergistic myelination	Technical complexity	Preclinical	Not studied	Not studied	Lopes et al. (2013)
Closed-Loop Systems	Advanced ES	Real-time adaptive stimulation	Personalized therapy	Early development	Preclinical	High (enhances ES)	Potential	Zhou et al. (2022)