Biomimetic dually cross-linked injectable poly(l-glutamic acid) based nanofiber composite hydrogels with self-healing, osteogenic and angiogenic properties for bone regeneration

Biomimetic hydrogels with satisfactory mechanical properties and osteogenic/angiogenic abilities have attracted extensive attention in recent years. Injectable hydrogels with the advantages of minimally invasive implantation and adaptability to irregular defects exhibit superior application potential in the field of bone regeneration. However, poor mechanical properties and limited self-healing ability hinder their potential as supporting materials. Furthermore, the absence of osteogenic and angiogenic properties significantly affect their application in bone regeneration. For injectable hydrogels, simulating natural bone tissue ECM presents an opportunity for developing innovative materials for bone repair. In this work, a strategy to prepare biomimetic nanofiber-reinforced dually cross-linked (DC) injectable hydrogels with self-healing, osteogenic and angiogenic properties was proposed. The PLGA/MDex/CaP@PBLG nanofiber hydrogels were crosslinked through two reversible dynamic interactions including Schiff base reaction and physical chelation, thereby demonstrating good self-healing property. Meanwhile, the incorporation of CaP@PBLG mineralized nanofibers and alendronate sodium (BP) grafted on PLGA could endow the hydrogels with favorable osteogenic function. Moreover, the introduction of antioxidant ferulic acid (FA) could significantly stimulate angiogenic activity of the hydrogels. The successful regeneration of cranial defects in rats demonstrated a potential application of PLGA/MDex/CaP@PBLG nanofiber hydrogels in the field of bone regeneration.