pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds
pH-Switchable Antimicrobial Nanofiber Networks of Hydrogel Eradicate Biofilm and Rescue Stalled Healing in Chronic Wounds
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DOI：
10.1021/acsnano.9b05608
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发表时间：
2019-10-01
期刊：
影响因子：
17.1
通讯作者：
Li, Yong-Qiang
中科院分区：
文献类型：
--
作者：
Wang, Jianhao;Chen, Xiao-Yi;Li, Yong-Qiang
生物被膜感染会导致慢性炎症，并阻碍正常的伤口愈合级联反应。在此，基于设计的八肽(IKFQFHFD)在中性pH下的自组装，报道了一种具有纳米纤维网络的pH可调抗菌水凝胶，用于清除生物膜和拯救慢性创面的迟缓愈合。这种水凝胶是生物相容的，并表现出酸性pH(感染的慢性伤口的病理环境)-可切换的广谱抗菌效果，其机制涉及细胞壁和膜的破坏。水凝胶的抗菌活性来源于其酸性的pH依赖的纳米纤维网络的不稳定和IKFQFHFD的活化释放，由于抗菌肽的分子结构，IKFQFHFD只有在酸性pH下才具有抗菌作用。此外，还进一步发展了以磷酸(光热剂)和脯氨酸(前胶原成分)为载体的超分子纳米纤维网络。体外实验表明，载药药物呈现酸性pH(pH类似于5.5)的响应性释放曲线，并在超分子纳米纤维网络的基础上实现了生物被膜的协同清除和随后的愈合级联激活细胞增殖。值得注意的是，水凝胶的纳米纤维网络可以在体内使糖尿病小鼠感染MRSA生物膜的伤口在20天内完全愈合，显示出作为慢性伤口敷料的巨大潜力。所提出的根除生物膜和激活随后的愈合级联的协同策略可能为临床慢性伤口的治疗提供一种强有力的方式。
Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH similar to 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.