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.