Assembly of Interfacial Polyelectrolyte Complexation Fibers with Mineralization Gradient for Physiologically-Inspired Ligament Regeneration

Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, interfacial polyelectrolyte complexation (IPC) spinning technique, along with a custom-designed collection system, to fabricate a hierarchical scaffold mimicking native ligament structure, is utilized. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite (HAp) mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor (CTGF) and conducting mesenchymal stem cells transplantation, the regenerative potential of the synthetic ligament is significantly amplified. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment. This work introduces a physiologically-inspired ligament regeneration with biomimetic hierarchical architecture, viscoelasticity, and enthesis-like mineralization gradient. Through these advancements, this research aims at improving clinical outcomes, facilitating patient recovery, and provide a long-lasting and effective solution for ligament injuries. image