Biomimetic hydrogel micro-/nanofibers for in situ soft tissue repair and regeneration

To effectively harness the regenerative potential of the body and orchestrate cellular responses for in situ tissue repair, the design of biomaterials requires careful consideration of precise modulation of biophysical and biochemical cues. This is essential to maximize the guidance of endogenous cell responses at the injury site. Hydrogel micro-/nanofibers, which integrate the benefits of hydrogel biomaterials and micro-/nanofiber architectures into a unified scaffold, have emerged as innovative biomimetic substrates that closely mimic the physiological characteristics of native extracellular matrix. These substrates exhibit tissue-like polymer networks, rapid responsiveness to microenvironmental changes, and permeability to essential nutrients and oxygen. Their biomimetic attributes facilitate cell recruitment and diffusion for angiogenesis, nutrient diffusion for cell self-renewal, and cell-material interactions for matrix remodeling, thus effectively harnessing the regenerative capacity of the body for tissue-specific regeneration. This review offers an overview of recent advances in hydrogel micro-/nanofiber design and their applications in in situ soft tissue engineering, focusing on: I) the concept and biomimetic characteristics of hydrogel micro-/nanofibers; II) current fabrication strategies, including material selection and preparation methods; and III) research progress in employing hydrogel micro-/nanofibers for in situ soft tissue regeneration, particularly in nerve, skin, cardiovascular, and skeletal muscle tissues. Overall, leveraging the body's regenerative potential through biomimetic hydrogel micro-/nanofibers represents an effective and promising approach for restoring damaged tissues. Additionally, this review provides valuable insights to foster interdisciplinary knowledge exchange and enables the development of prognostic markers for the next generation of hydrogel micro-/nanofibers to accelerate soft tissue regeneration.