A modular self-assembling peptide platform targeting TGF-β1 for tendon regeneration.

Excessive transforming growth factor-β1 (TGF-β1) signaling is a key driver of the pathological processes of fibrosis and matrix disorganization in tendinopathy, yet current treatments do not directly target this fibrotic microenvironment. Here we show that a self-assembling peptide composed entirely of natural amino acids, AsPep-FTSQ, can locally capture TGF-β1 and remodel the pathological tendon niche. Injecting AsPep-FTSQ into rat and beagle models of tendinopathy resulted in the formation of an interconnected nanofibrous network in situ that selectively sequesters excess TGF-β1. This network suppresses pro-fibrotic signaling, limits pathological tendon cell (TC) state transitions, and promotes collagen realignment. These effects improve tendon structure and functional repair across species. This fully natural, self-assembling peptide composed of amino acids provides a modular strategy for local cytokine sequestration and suggests a therapeutic approach for tendinopathy and potentially other fibrotic soft-tissue disorders.