Multifunctional naturally derived bioadhesives: From strategic molecular design toward advanced biomedical applications

In the last decades, adhesives derived from natural resources (i.e., bioadhesives) have emerged as promising alternative to the standard wound closure devices, including sutures, clips, and strips, owing to relatively easy and rapid application, minimal tissue damage, fast hemostasis, and ability to decrease the risk of infection. Various synthetic and natural materials have been utilized as bioadhesives. These materials find extensive applications in various biomedical fields, ranging from simple wound sealing to controlled drug delivery, tissue regeneration, and noninvasive therapy. Considering the weak underwater adhesion, degradability, and biological performances of synthetic adhesives, naturally derived-based adhesives are more attractive. The first generation of these bioadhesives provided primarily only one function. Moreover, they had issues including long curing time, slow adhesion, high degradation rate, low mechanical properties, and the risk of transferring contamination to the wound. Various chemically and genetically engineered strategies have been applied to advance their multifunctionality. The synergy of bonding chemistry, topography, and mechanics of dissipation in their structure supports the improved adhesion and controlled degradation rate. Various naturally derived bioadhesives are developed that cover subjects from innovative biomaterial synthesis or functionalization and cutting-edge manufacturing processes. However, to fulfill all the criteria of an ideal bioadhesive for clinical applications, more efforts should be devoted to investigating the surface characteristics of target tissues and the long-term relationship between the physiochemical properties of natural polymers and cohesion and adhesion mechanisms, as well as adhesive functionality. This review outlines the recent progress on naturally-derived bioadhesives, including proteins and polysaccharides, focusing on designing approaches based on chemically and genetically engineering strategies, development, and applications. Furthermore, the challenges of current studies are summarized to show future perspectives for developing bioengineered and high-performance naturally-derived bioadhesives for clinical use.