Regenerative Nanoscaffolds for Chronic Tympanic Membrane Perforation: From Bench to Clinical Translation

Abstract

Chronic tympanic membrane (TM) perforation remains difficult to resolve without surgery because of poor intrinsic healing capacity and limitations of passive, nonsurgical materials. Although patch-based approaches are common, most merely provide passive coverage and lack intrinsic therapeutic capability to drive tissue regeneration. We developed and clinically evaluated an extracellular matrix (ECM)-mimetic, drug-free nanopattern guidance (NG) patch for TM repair, marking a paradigm shift from passive coverage to active, biophysically driven regeneration. The NG patch is a biocompatible, implantable scaffold with aligned nanotopography that recapitulates native ECM architecture, coupled with a hydrocolloid adhesive layer to ensure secure placement. In a prospective study of 18 patients, the NG patch achieved a 61% overall healing rate with 50% complete closure and no serious adverse events. In rat models, a single application induced complete healing within 2 weeks. Mechanistic in vitro assays demonstrated that the nanopatterned surface enhances fibroblast adhesion, alignment, and directional migration, supporting organized tissue closure. Collectively, the NG patch offers a minimally invasive approach that activates TM repair through physical cues without exogenous drugs. This first clinical evaluation of an ECM-mimetic nanotopographical scaffold introduces a strategy to redefine the standard of care for chronic TM perforation and related defects.

Impact Statement

We report the first clinical evaluation of a drug-free, extracellular matrix-mimetic nanotopographical scaffold for chronic tympanic membrane perforation, shifting treatment from passive patching to active, biophysically guided regeneration. The nanopattern guidance (NG) patch combines aligned poly(lactic-co-glycolic acid) (PLGA) nanotopography with a hydrocolloid adhesive layer to promote fibroblast alignment/migration and maintain stable tympanic membrane contact. In a prospective study, it achieved a 61% overall healing rate (50% complete closure) without serious adverse events, with rapid and complete healing in animal models. This platform establishes a minimally invasive, clinically translatable strategy for otologic membrane repair.