Alanine-modified cellulose nanofibril hydrogel bioadhesives: An injectable angiogenic platform for promoting wound healing

Injectable hydrogels have gained considerable attention as sutureless bioadhesives for minimally invasive wound closure, owing to their ability to adapt to complex wound geometries. However, upon application, these biomaterials can occupy the wound space, potentially hindering critical healing processes such as angiogenesis and granulation tissue formation. To overcome this challenge, we developed a greener synthesis route for the fabrication of alanine-modified cellulose nanofibrils (Ala-CNFs). Compared with traditional cellulose modification strategies, this route eliminates the need for cytotoxic reagents and metal catalysts that are indispensable for conventional approaches. The Ala-CNFs formed a versatile hydrogel via crosslinking with polyvinyl alcohol (PVA) and phenylboronic acid modified cyclodextrin (PBCD) (denoted as Ala-CNFs@PVA/PBCD). Furthermore, the Ala-CNFs@PVA/PBCD hydrogel integrates multiple essential functionalities, including injectability, self-healing, biodegradability, and shape adaptability. Ala-CNFs served a dual function: (i) they enhanced adhesion, enabling the hydrogel to achieve rapid hemostasis in cardiac (38 s) and even femoral artery (34 s) wounds, and (ii) they actively promoted angiogenesis and granulation tissue infiltration within its macroporous matrix, thereby addressing the critical issue of physical barrier posed by conventional injectable adhesives. Consequently, this work not only provides a novel synthesis strategy for functionalized cellulose but also presents a sustainable and multifunctional strategy for advanced wound management, particularly suitable for emergency scenarios such as warfare and earthquakes.