Bioinspired Intrinsic Versatile Hydrogel Fabricated by Amyloidal Toxin Simulant‐Based Nanofibrous Assemblies for Accelerated Diabetic Wound Healing

Abstract

Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH 2 , FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillinresistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drugrelated side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the manage ment of microbeinfected diabetic wounds.

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice

“…The matrix facilitates signaling among micro-organisms by producing population-sensing molecules. This cross-communication can further aid microbial proliferation, optimize nutrient uptake and regulate virulence, leading to a persistent impairment of wound healing [ 29 , 30 , 32 ]. Bacterial endotoxin- and exotoxin-associated wound infections are found to induce non-specific and specific immune responses [ 33 ], while excessive inflammation can further trigger adverse outcomes, where inflammatory cells recruited at the wound site produce large amounts of proteases that degrade the extracellular matrix and delay wound healing [ 34 ].…”

Biomaterials to promote vascularization in tissue engineering organs and ischemic fibrotic diseases

“…Copyright permission from Yao et al 52 (C) Representative snapshots of structure of peptide assembly and the schematic of angiogenesis mechanism of Fmoc‐lfkffk‐nh2 (FLN)‐based hydrogel. Copyright permission from Xuan et al 53 (D) Schematic diagram showing the application of Chinese herb microneedle (CHMN) patch derived from the extractives of Chinese herbs. Copyright permission from Chi et al 54 (E) Schematic diagram of self‐healing mechanism.…”

“…The truncated peptide (LK) is a self‐assembled polypeptide that can self‐assemble into nanofibers and further wrap it to form a hydrogel matrix (Figure 2C). The amyloid structure of the truncated peptide (LK) promotes the high expression of hypoxia‐induced factor 1 and VEGFA signals, accelerates angiogenesis, and promotes skin wound healing 53 . Two traditional Chinese herbs, Premna microphylla and Centella asiatica have the ability to promote the expression of related growth factor genes in fibroblasts (Figure 2D).…”

“…The amyloid structure of the truncated peptide (LK) promotes the high expression of hypoxia-induced factor 1 and VEGFA signals, accelerates angiogenesis, and promotes skin wound healing. 53 Two traditional Chinese herbs, Premna microphylla and Centella asiatica have the ability to promote the expression of related growth factor genes in fibroblasts (Figure 2D). Integrating Chinese herbs into the microneedle mold, the constructed Chinese herb microneedle patch significantly promoted neovascularization and granulation tissue formation.…”

Mussel-inspired multifunctional hydrogel dressing with hemostasis, hypoglycemic, photothermal antibacterial properties on diabetic wounds

“…These infections can aggravate the inflammatory response, which will worsen the wounds, and prolong the healing time. 1,2 Besides, biofilms have been shown to exist in more than 90% of the diabetic chronic wounds and they are formed by bacteria in many environments, which are packed together by extracellular polymeric substances (EPS) existing as complex surface-attached communities. 3 The biofilms on the surfaces of wounds can protect potential microorganisms from antibiotic treatment and promote the development of drugresistant bacteria.…”