Bioactive insulin-loaded electrospun wound dressings for localized drug delivery and stimulation of protein expression associated with wound healing

Effective therapy of wounds is difficult, especially for chronic, non-healing wounds, and novel therapeutics are urgently needed. This challenge can be addressed with bioactive wound dressings providing a microenvironment and facilitating cell proliferation and migration, ideally incorporating actives which initiate and/or progress effective healing upon release. In this context, electrospun scaffolds loaded with growth factors emerged as promising wound dressings due to their biocompatibility, similarity to the extracellular matrix and potential for controlled drug release. In this study, electrospun core-shell fibers were designed composed of a combination of polycaprolactone and polyethylene oxide. Insulin, a proteohormon with growth factor characteristics, was successfully incorporated into the core and was released in a controlled manner. The fibers exhibited favorable mechanical properties and a surface guiding cell migration for wound closure in combination with a high uptake capacity for wound exudate. Biocompatibility and significant wound healing effects were shown in interaction studies with human skin cells. As a new approach, analysis of the wound proteome in treated ex vivo human skin wounds clearly demonstrated a remarkable increase in wound healing biomarkers. Based on these findings, insulin-loaded electrospun wound dressings bear a high potential as effective wound healing therapeutics overcoming current challenges in the clinics.

伤口的有效治疗极具挑战性，尤其是慢性难愈伤口，因此亟需开发新型治疗手段。该难题可通过生物活性伤口敷料加以破解：这类敷料能够营造适宜的伤口微环境，促进细胞增殖与迁移，理想状态下还可负载活性成分，使其在释放后启动并推进高效的伤口愈合过程。在此研究背景下，负载生长因子的静电纺丝（electrospun）支架凭借其生物相容性、与细胞外基质（extracellular matrix）的高度相似性以及可控释药的潜力，成为极具应用前景的伤口敷料候选方案。本研究中，研究人员设计了由聚己内酯（polycaprolactone，PCL）与聚环氧乙烷（polyethylene oxide，PEO）复合制备的静电纺丝核壳纤维。具有生长因子特性的蛋白激素（proteohormon）胰岛素被成功负载至纤维芯层，并以可控方式实现释放。该纤维材料展现出优良的力学性能，其表面可引导细胞迁移以助力伤口闭合，同时对伤口渗出液具备较高的吸收能力。通过与人体皮肤细胞的交互实验，证实了该敷料的生物相容性与显著的伤口愈合效果。作为一项全新研究策略，对经处理的离体（ex vivo）人体皮肤伤口进行伤口蛋白质组分析，结果清晰显示伤口愈合相关生物标志物的水平得到了显著提升。基于上述研究结果，负载胰岛素的静电纺丝伤口敷料具备极高的应用潜力，可作为高效的伤口愈合治疗手段，解决当前临床中面临的相关难题。