Tough and hierarchically-structured silk hydrogel for artificial tendons

Tendon injuries are prevalent in both athletic and general populations, leading to significant pain, lost productivity, and disabilities. However, surgical reconstruction of ruptured tendons remains a clinical challenge and requires tough, regenerative artificial tendons to promote functional restoration. Here, inspired by the structure of native tendons, we introduce a facile approach that synergistically combines directional-freezing and hot-stretching strategies to produce tough and hierarchically-structured silk hydrogels, named DFHS hydrogels, for artificial tendons. At a high water content of about 70 wt%, DFHS hydrogels exhibit an ultimate tensile strength of 13.9 MPa, comparable to human anterior cruciate ligament, and a fracture toughness of 45.5 kJ m^-2, 5 times as high as natural rubber. Additionally, the high crystallinity and aligned multi-level structures prolong the degradation and thus improve long-term integrity and mechanical stability both in vitro and in vivo. DFHS hydrogels exhibit multi-level anisotropy, featuring micrometer-scale honeycomb-like pore walls that harbor nanoscale-oriented β-sheets. These bioinspired topological niches induce significant cell alignment, guide the ingrowth of neo-tendon, upregulate pathways related to the extracellular matrix, promote mature tendon formation, and thereby facilitate tendon healing. This strategy, transferable to other semicrystalline polymers, presents a water-based fabrication approach for the development of tough hydrogels toward clinical translations.