Key Takeaways & Executive Findings
- •• • Ultrafast gelation: MPAH achieves gelation within 2 s under UV irradiation, outperforming commercial fibrin glues and enabling rapid sealing in clinical settings to mitigate hemorrhage and infection risks. • • Low swelling: Equilibrium swelling ratio below 30% in PBS over 16 days, preventing tissue compression and interfacial detachment, which is critical for maintaining adhesive integrity in wet, dynamic environments. • • Robust mechanical properties: Lap shear strength of ~35 kPa on wet porcine casings, extensibility exceeding 60%, and compressive strength of ~475 kPa, ensuring stable adhesion and mechanical reinforcement in moist tissues. • • Enhanced wound healing: In rat models, MPAH reduced inflammation and accelerated re-epithelialization compared to fibrin glue and sutures, demonstrating superior sealing and regenerative outcomes.
Abstract
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.
1. Introduction
Current wound closure methods, including sutures and staples, are invasive and often fail to provide immediate sealing, particularly in irregular or fragile tissues. Bioadhesives offer a minimally invasive alternative, but existing hydrogel adhesives suffer from excessive swelling, which weakens cohesion and disrupts adhesion, leading to secondary tissue damage. Commercial fibrin glues exhibit weak cohesion and adhesion, limiting their efficacy in wet, dynamic environments.
This research introduces MPAH, a hyaluronic acid-based bioadhesive engineered with hydrophobic phenylalanine groups and NHS esters. The design leverages hydrophobic interactions and π-π stacking to achieve ultrafast photo-crosslinking (2 s), low swelling (<30% over 16 days), and robust mechanical performance (lap shear ~35 kPa, compressive strength ~475 kPa). These properties address the critical bottleneck of swelling-induced instability, offering a reliable solution for rapid wound closure and tissue repair in complex clinical conditions.
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Pan Sun, Jiadong Wu, Xianjia Lin, Yang Tian, Jing Sun (2026). Engineering an Ultrafast Gelling and Low Swelling Hyaluronic Acid Bioadhesive for Stable Wet-Tissue Adhesion and Enhanced Wound Healing. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3996-x
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Frequently Asked Questions
What is the mechanism behind the low swelling behavior of MPAH, and how does it prevent interfacial detachment?
The low swelling is attributed to hydrophobic interactions and π-π stacking among phenylalanine groups, which create a dense network that limits water uptake. This maintains cohesive strength and prevents volumetric expansion, thereby avoiding tissue compression and interfacial detachment.
How does the gelation time of MPAH compare to commercial fibrin glues, and what are the clinical implications?
MPAH gels within 2 s under UV irradiation, significantly faster than fibrin glues. This rapid curing enables immediate sealing, reducing operative time and risk of hemorrhage and infection, particularly in acute wounds.
What are the mechanical properties of MPAH under wet conditions, and how do they translate to in vivo performance?
MPAH exhibits a lap shear strength of ~35 kPa on wet porcine casings, extensibility >60%, and compressive strength ~475 kPa. These properties ensure stable adhesion and mechanical reinforcement in moist, dynamic tissues, as evidenced by accelerated wound healing in rat models.
What is the synthetic scalability of MPAH, and does the hydrophobic modification strategy offer cost advantages?
The chemical synthesis is straightforward and scalable, with the hydrophobic modification strategy providing a cost-effective pathway for producing advanced functional biomaterials, as stated in the paper.
How does MPAH compare to sutures in terms of wound healing outcomes?
In rat models, MPAH demonstrated reduced inflammation and accelerated re-epithelialization compared to sutures, indicating superior sealing and regenerative support, likely due to its rapid adhesion and low swelling properties.
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