IntroductionThe objective of this study is to stimulate wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF).Materials and methodsInspired by the crosslinking mechanism in algae-based adhesives, hydrogels were fabricated with gum arabic, pectin, and Ca2+. The physical properties of the bioinspired hydrogels were characterized, and the in vitro release of bFGF was investigated. Then, the in vitro scratch assay for wound healing and in vivo wound healing experiment in a full-thickness excision wound model were performed for the bioinspired hydrogels with bFGF. Finally, histological examinations and organ toxicity tests were conducted to investigate the wound healing applications of the bioinspired hydrogels with bFGF.ResultsThe in vitro and in vivo results showed that the bioinspired hydrogels with bFGF could significantly enhance cell proliferation, wound re-epithelialization, collagen deposition, and contraction without any noticeable toxicity and inflammation compared with the hydrogels without bFGF and commercial wound healing products.ConclusionThese results suggest the potential application of bioinspired hydrogels with bFGF for wound healing.

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Bai J andWang ZY conceived and designed the study; Bai J, Chen WB, and Zhang XY performed the experiments; Zhang XY and Kang XN acquired the patients' data; Bai J, Kang XN, Jin LJ, and Zhang H analyzed the data and drafted the report; Wang ZY supervised the study; all authors reviewed and revised the manuscript critically and approved the final version to be published. Institutional review board statement:The study was approved by the Ethics Committee of Cangzhou Central Hospital.

We found that use of an intra-abdominal FDG uptake cut-off value for SUVmax of >5.1 assists in the diagnosis of peritoneal carcinomatosis. FDG PET may play an important role in the clinical management of patients with suspected peritoneal carcinomatosis.

Membrane-disruptive, drug-free macromolecular therapeutics may help overcome cancer drug-resistance. Their inability to distinguish cancerous from normal cells, however, results in significant off-target toxicity. Note that the tumor has a slightly acidic microenvironment (pH 6.5–6.8) in contrast to the alkaline microenvironment in normal tissues (pH 7.4) and that host-defense peptides (HDPs) and their synthetic mimetics need to be net cationic to be membrane-disruptive. We herein endow polymer mimetics of HDPs with acid-triggered cationicity, to make them membrane-disruptive at only tumor pH. For these polymer mimetics, there exists a maximal threshold of chain length that determines whether the micelle of a mimetic inherits its pH-sensitive activity. Using the most and least active micelles as representatives, we find that their distinct potency in disrupting membranes arises because of their striking tendency to dissociate upon exposure to tumor pH. As expected, these micelles exhibit in vitro cytotoxicity profiles that correlate with their membrane-disruptive activity profiles. When administered intravenously, these micellesirrespective of their distinct activity profilesunanimously exhibit long systemic circulation as do PEGylated micelle nanoparticles, despite of their lacking stealth materials, owing to the zwitterionic nature of their surfaces at blood pH. Nevertheless, the pH-sensitive micelle achieves significantly higher tumor uptake and strikingly better therapeutic efficacy than its completely inactive analogue. More important, the pH-sensitive micelle exhibits undetectable off-target toxicity, owing to its pH-sensitivity. Clearly, making HDPs and their mimetics sensitive to tumor-characteristic cues (e.g., acidic pH) is efficient in minimizing their off-target toxicity, thereby offering membrane-disruptive, drug-free macromolecular therapeutics for fighting against cancer drug-resistance.