Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisboa, 1649-003, Portugal.
Adv Healthc Mater. 2023 Nov;12(28):e2301513. doi: 10.1002/adhm.202301513. Epub 2023 Aug 10.
The optimized physical adhesion between bees' leg hairs and pollen grains-whereby the latter's diameter aligns with the spacing between the hairs-has previously inspired the development of a biomimetic drug dressing. Combining this optimized process with the improved natural mussels' adhesion in wet environments in a dual biomimetic process, it is herein proposed the fabrication of a natural-derived micropatterned hydrogel patch of methacrylated laminarin (LAM-MET), with enriched drug content and improved adhesiveness, suitable for applications like wound healing. Enhanced adhesion is accomplished by modifying LAM-MET with hydroxypyridinone groups, following the patch microfabrication by soft lithography and UV/vis-irradiation, resulting in a membrane with micropillars with a high aspect ratio. Following the biomimetics rational, a drug patch is engineered by combining the microfabricated dressing with drug particles milled to fit the spaces between pillars. Controlled drug release is achieved, together with inherent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, and enhanced biocompatibility using the bare micropatterned patches. This new class of biomimetic dressings overcomes the challenges of current patches, like poor mechanical properties and biocompatibility, limited adhesiveness and drug dosage, and lack of prolonged antimicrobial activity, opening new insights for the development of high drug-loaded dressings with improved patient compliance.
蜜蜂腿毛与花粉粒之间优化的物理附着力——花粉粒的直径与腿毛之间的间距相吻合——此前曾启发人们开发出仿生药物敷料。在双仿生过程中将这种优化的过程与在潮湿环境中提高的天然贻贝附着力相结合,本文提出了一种天然衍生的甲基丙烯酰化海藻酸盐(LAM-MET)的微图案水凝胶贴剂的制造方法,该贴剂具有丰富的药物含量和增强的粘附性,适用于伤口愈合等应用。通过用羟基吡啶酮基团修饰 LAM-MET 来实现增强的附着力,然后通过软光刻和 UV/可见光照射进行贴剂微制造,从而得到具有高纵横比的微柱形膜。根据仿生学原理,通过将微加工敷料与磨碎至适合柱间空间的药物颗粒结合,设计出药物贴剂。通过使用裸微图案化贴剂实现了药物的控制释放以及对大肠杆菌和铜绿假单胞菌的固有抗菌活性,并提高了生物相容性。这种新型仿生敷料克服了当前贴剂的挑战,如机械性能和生物相容性差、附着力和药物剂量有限以及缺乏长效抗菌活性等,为开发具有改善的患者依从性的高载药量敷料提供了新的思路。