Engineering an Ultrafast Gelling and Low Swelling Hyaluronic Acid Bioadhesive for Stable Wet-Tissue Adhesion and Enhanced Wound Healing
Bioadhesives that rapidly and reliably seal wet tissues remain a formidable challenge due to the trade-off between mechanical compliance and swelling-induced instability in physiological environments. To address this limitation, we report a hydrophobic effect-mediated bioadhesive, consisting of methacrylated phenylalanine hyaluronic acid (HA) adhesive (MPAH), which integrates ultrafast photo-crosslinking with strong tissue adhesion and low swelling. Through the synergistic incorporation of hydrophobic phenylalanine groups and N-hydroxysuccinimide (NHS) esters, MPAH forms gelation within 2 s under UV irradiation, significantly outperforming commercial fibrin glues. The adhesive shows a lap shear strength of ~35 kPa on wet porcine casings, an extensibility exceeding 60%, and a compressive strength of ~475 kPa. In contrast to conventional HA hydrogels and commercial fibrin glues, MPAH maintains a low equilibrium swelling ratio below 30% in PBS over 16 days. This behavior is attributed to hydrophobic interactions and π-π stacking within the network, effectively preventing tissue compression and interfacial detachment. In rat wound models of linear incision and full-thickness skin defects, MPAH demonstrated rapid sealing, reduced inflammation, and accelerated re-epithelialization compared to fibrin glue and sutures, highlighting its potential as an effective bioadhesive for wound closure and soft tissue repair.