Supramolecularly Reinforced Hydrogel Scaffolds for Advanced Tissue Engineering

The regeneration of articular cartilage is hindered by the absence of intrinsic repair mechanisms and the lack of scaffolds that integrate both biochemical functionality and mechanical resilience. Conventional hydrogels capture certain aspects of the native niche yet remain limited by weak supramolecular cohesion and insufficient load-bearing capacity. To overcome these barriers, a hybrid hydrogel was engineered by coupling decellularized cartilage extracellular matrix (dECM) with the self-assembling peptide: fluorenylmethoxycarbonyl-modified amino acids (Fmoc-xx). Hydrogels derived from dECM retain native proteins and signaling motifs but typically collapse under physiological stresses, restricting their therapeutic value. While dECM offers native adhesion sites and instructive biochemical cues, Fmoc-xx nanofibers form a supramolecular framework that interpenetrates ECM macromolecules through hydrogen bonding and aromatic π–π stacking. These cooperative interactions generate a hierarchically organized network that transforms the mechanically fragile dECM hydrogel into a resilient, load-bearing construct. This molecular reinforcement elevated the storage modulus by nearly three orders (~1000 fold increase) of magnitude while preserving hydration and network stability. Furthermore, the hybrid scaffold provided a cell-compatible niche that enabled rapid chondrocyte adhesion as well as sustained proliferation. The hybrid hydrogel could maintain the chondrogenic phenotype, underscoring the synergy between structural resilience and biological fidelity. By uniting supramolecular self-assembly with native matrix bioactivity, this work advances a materials strategy that converts fragile dECM gels into robust, functional scaffolds. Such reinforced hydrogels do not merely mimic tissue microenvironments but actively integrate strength with bioactivity, positioning them as next-generation platforms for cartilage regeneration and broader tissue engineering applications.