Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering and Research Centre for Biomedical Engineering, Universitat Politècnica de Catalunya BarcelonaTech (UPC), 08019 Barcelona, Spain.
Barcelona Research Centre in Multiscale Science and Engineering, Universitat Politècnica de Catalunya BarcelonaTech (UPC), 08019 Barcelona, Spain.
Biomater Sci. 2023 Jul 12;11(14):4845-4858. doi: 10.1039/d3bm00212h.
In the last decades, non-thermal plasma has been extensively investigated as a relevant tool for various biomedical applications, ranging from tissue decontamination to regeneration and from skin treatment to tumor therapies. This high versatility is due to the different kinds and amount of reactive oxygen and nitrogen species that can be generated during a plasma treatment and put in contact with the biological target. Some recent studies report that solutions of biopolymers with the ability to generate hydrogels, when treated with plasma, can enhance the generation of reactive species and influence their stability, resulting thus in the ideal media for indirect treatments of biological targets. The direct effects of the plasma treatment on the structure of biopolymers in water solution, as well as the chemical mechanisms responsible for the enhanced generation of RONS, are not yet fully understood. In this study, we aim at filling this gap by investigating, on the one hand, the nature and extent of the modifications induced by plasma treatment in alginate solutions, and, on the other hand, at using this information to explain the mechanisms responsible for the enhanced generation of reactive species as a consequence of the treatment. The approach we use is twofold: (i) investigating the effects of plasma treatment on alginate solutions, by size exclusion chromatography, rheology and scanning electron microscopy and (ii) study of a molecular model (glucuronate) sharing its chemical structure, by chromatography coupled with mass spectrometry and by molecular dynamics simulations. Our results point out the active role of the biopolymer chemistry during direct plasma treatment. Short-lived reactive species, such as OH radicals and O atoms, can modify the polymer structure, affecting its functional groups and causing partial fragmentation. Some of these chemical modifications, like the generation of organic peroxide, are likely responsible for the secondary generation of long-lived reactive species such as hydrogen peroxide and nitrite ions. This is relevant in view of using biocompatible hydrogels as vehicles for storage and delivery reactive species for targeted therapies.
在过去的几十年中，非热等离子体已被广泛研究，作为各种生物医学应用的相关工具，范围从组织净化到再生，从皮肤处理到肿瘤治疗。这种多功能性归因于在等离子体处理过程中可以产生的不同种类和数量的活性氧和氮物种，并与生物靶标接触。一些最近的研究报告称，具有生成水凝胶能力的生物聚合物溶液在经过等离子体处理后，可以增强活性物质的生成并影响其稳定性，从而成为间接处理生物靶标的理想介质。等离子体处理对水溶液中生物聚合物结构的直接影响，以及导致 RONS 生成增强的化学机制，尚未得到充分理解。在这项研究中，我们旨在通过研究一方面研究等离子体处理在藻酸盐溶液中诱导的修饰的性质和程度，另一方面利用这些信息来解释处理后活性物质生成增强的机制，来填补这一空白。我们采用的方法是双重的：（i）通过尺寸排阻色谱法、流变学和扫描电子显微镜研究等离子体处理对藻酸盐溶液的影响，（ii）通过色谱法与质谱联用和分子动力学模拟研究具有化学结构相似的分子模型（葡萄糖醛酸）。我们的研究结果指出了生物聚合物化学在直接等离子体处理过程中的积极作用。短寿命的活性物质，如 OH 自由基和 O 原子，可以修饰聚合物结构，影响其官能团并导致部分碎片化。这些化学修饰中的一些，如有机过氧化物的生成，可能是导致过氧化氢和亚硝酸盐等长寿命活性物质二次生成的原因。这对于使用生物相容性水凝胶作为储存和输送活性物质进行靶向治疗的载体具有重要意义。
