Stager Michael A, Bardill James, Raichart Alexandra, Osmond Matthew, Niemiec Stephen, Zgheib Carlos, Seal Sudipta, Liechty Kenneth W, Krebs Melissa D
Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States.
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado 80217, United States.
ACS Appl Bio Mater. 2022 Mar 21;5(3):1092-1103. doi: 10.1021/acsabm.1c01155. Epub 2022 Feb 15.
In the United States, $87 billion per year is spent on the care of diabetic ulcers alone. Although the pathophysiology of diabetic wound healing is multifaceted, high systemic levels of inflammation and increased reactive oxygen species are often implicated in the wound healing impairment. Zwitterionic materials have been demonstrated to reduce inflammation and increase extracellular matrix deposition in wound beds, and here, we demonstrate a fabrication method for photopolymerized zwitterionic hydrogels that also enables sustained drug delivery over time. A therapeutic molecule of interest that is examined in this work is cerium oxide nanoparticle tagged with microRNA-146a (CNP-miR146a) to combat both oxidative stress and inflammation. The hydrogels are composed of zwitterionic and nonzwitterionic monomers, and the hydrogel formation occurs in the absence of a crosslinker. The hydrogels exhibit a wide range of stiffness and mechanical properties depending on their monomer content. Additionally, these hydrogels exhibit sustained release of nanoparticles and proteins. Finally, when employed in an diabetic mouse wound healing model, the zwitterionic hydrogels alone and laden with the CNP-miR146a conjugate significantly improved the rate of diabetic wound healing. Overall, these materials have excellent potential to be used as a topical treatment for chronic diabetic wounds.
在美国，仅每年用于治疗糖尿病溃疡的费用就达870亿美元。尽管糖尿病伤口愈合的病理生理学是多方面的，但全身性炎症水平升高和活性氧增加常被认为与伤口愈合受损有关。两性离子材料已被证明可减轻炎症并增加伤口床中的细胞外基质沉积，在此，我们展示了一种用于光聚合两性离子水凝胶的制备方法，该方法还能实现药物的持续递送。在这项研究中检测的一种感兴趣的治疗分子是标记有微小RNA-146a的氧化铈纳米颗粒（CNP-miR146a），用于对抗氧化应激和炎症。水凝胶由两性离子和非两性离子单体组成，水凝胶的形成在没有交联剂的情况下发生。根据单体含量，水凝胶表现出广泛的硬度和机械性能。此外，这些水凝胶表现出纳米颗粒和蛋白质的持续释放。最后，当应用于糖尿病小鼠伤口愈合模型时，单独的两性离子水凝胶以及负载CNP-miR146a偶联物的水凝胶显著提高了糖尿病伤口的愈合速度。总体而言，这些材料作为慢性糖尿病伤口的局部治疗具有巨大潜力。
