Anti-oxidant anti-inflammatory and antibacterial tannin-crosslinked citrate-based mussel-inspired bioadhesives facilitate scarless wound healing.

The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

High-Performance Polymeric Materials through Hydrogen-Bond Cross-Linking.

It has always been critical to develop high-performance polymeric materials with exceptional mechanical strength and toughness, thermal stability, and even healable properties for meeting performance requirements in industry. Conventional chemical cross-linking leads to enhanced mechanical strength and thermostability at the expense of extensibility due to mutually exclusive mechanisms. Such major challenges have recently been addressed by using noncovalent cross-linking of reversible multiple hydrogen-bonds (H-bonds) that widely exist in biological materials, such as silk and muscle. Recent decades have witnessed the development of many tailor-made high-performance H-bond cross-linked polymeric materials. Here, recent advances in H-bond cross-linking strategies are reviewed for creating high-performance polymeric materials. H-bond cross-linking of polymers can be realized via i) self-association of interchain multiple H-bonding interactions or specific H-bond cross-linking motifs, such as 2-ureido-4-pyrimidone units with self-complementary quadruple H-bonds and ii) addition of external cross-linkers, including small molecules, nanoparticles, and polymer aggregates. The resultant cross-linked polymers normally exhibit tunable high strength, large extensibility, improved thermostability, and healable capability. Such performance portfolios enable these advanced polymers to find many significant cutting-edge applications. Major challenges facing existing H-bond cross-linking strategies are discussed, and some promising approaches for designing H-bond cross-linked polymeric materials in the future are also proposed.