Structure–property relationships and biological performance of electroactive biomaterial scaffolds for tissue regeneration

Electroactive biomaterials represent a novel branch of functional biomaterials, which can integrate electrical conductivity with mechanical strength or structural integrity in regenerative matrices. In this review, electroactive scaffolds are discussed within a structure–property–function paradigm with special emphasis on the influence of material composition, scaffold architecture, interfacial chemistry, conductivity, mechanical compliance, biodegradation behavior, and mode of stimulation on cell outcomes. Polymers on conducting, piezoelectric composites, iono-active hydrogels, carbon-based nanomaterials and hybrid systems are discussed about charge transport, biocompatibility, biodegradability, electrochemical stability and potential for translation limitations. Fabrication techniques such as electrospinning, additive manufacturing (3D printing), lithographic patterning and hydrogel hybridization have been assessed based on replication, scalability and tissue type specific design attribute. The review also addresses mechanistic correlations between scaffold features, cell adhesion, proliferation, lineage differentiation, ion-channel activity, cytoskeletal organization, and gene expression. In addition, the review includes preclinical evidence, the status of clinical trials, the regulatory classification, the constraints of manufacturing and the financial considerations. In conclusion, electroactive scaffolds present exciting opportunities for tissue regeneration; however, translation will be enhanced by more rigorous quantitative reporting, demonstration of long-term safety, establishment of standardized scaffold fabrication protocols, and realistic renditions of translation.