In situ fluid-to-solid converting injectable wet adhesive for comminuted fracture repair via water-activated bonding

Comminuted fractures, characterized by multiple irregular bone fragments, present significant challenges for traditional fixation methods like plates and screws, often resulting in complex surgeries and delayed healing. Injectable hydrogel adhesives have been applied for comminuted fractures, but face challenges such as excessive fluidity before curing and curing processes that involve high temperatures or ionic release, which can result in material leakage, localized inflammation and reduced adhesion. To address these challenges, we developed a humidity-responsive hydrogel adhesive system, comprised of tannic acid (TA), silk fibroin (SF), amorphous calcium phosphate (ACP), and guanidine hydrochloride (GuCl). GuCl acts as a hydrogen bond disruptor, which enables faster and more complete penetration of the hydrogels into bone fragments. Upon exposure to body fluids, GuCl diffuses out, allowing hydrogen bonds to reform. This process enabled the hydrogel to dynamically transition from a low-modulus, injectable state to a high-modulus, adhesive gel. Moreover, the presence of ACP enhanced the mechanical and mineralization properties of the hydrogel. The resultant hydrogel showed desirable biocompatibility and osteogenic properties, both in vitro and in vivo. Collectively, this research addressed the critical issue of the difficulty of injectable bone bonding materials to penetrate irregular bone fragments and maintain good biocompatibility while rapidly solidifying in situ. This system demonstrates significant potential for clinical application in the effectively treatment of complex bone injuries, especially for in situ repair of comminuted fractures. STATEMENT OF SIGNIFICANCE: Comminuted fractures involve multiple irregular bone fragments, posing serious challenges for fixation using traditional hardware. Existing injectable adhesives often suffer from poor cohesion, inflammatory side effects, and inadequate curing control. We present a moisture-responsive hydrogel adhesive (rTSA-G), composed of tannic acid, silk fibroin, amorphous calcium phosphate, and guanidine hydrochloride. This system exhibits high injectability, transitions rapidly to a solid upon contact with water, and provides strong adhesion, mechanical support, and osteoinductive properties. By addressing the key limitations of current bone adhesives, this strategy offers a promising alternative for minimally invasive treatment of complex fractures and advances the development of next-generation stimulus-responsive biomaterials.