Department of Chemistry and Physics of Surfaces and Biointerfaces, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic.
Department of Biomaterials and Tissue Engineering, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Int J Nanomedicine. 2023 Feb 3;18:595-610. doi: 10.2147/IJN.S393890. eCollection 2023.
The formation of diabetic ulcers (DU) is a common complication for diabetic patients resulting in serious chronic wounds. There is therefore, an urgent need for complex treatment of this problem. This study examines a bioactive wound dressing of a biodegradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) covered by a thin fibrin layer for sustained delivery of bioactive molecules.
Electrospun PLCL/PCL nanofibers were coated with fibrin-based coating prepared by a controlled technique and enriched with human platelet lysate (hPL), fibroblast growth factor 2 (FGF), and vascular endothelial growth factor (VEGF). The coating was characterized by scanning electron microscopy and fluorescent microscopy. Protein content and its release rate and the effect on human saphenous vein endothelial cells (HSVEC) were evaluated.
The highest protein amount is achieved by the coating of PLCL/PCL with a fibrin mesh containing 20% v/v hPL (NF20). The fibrin coating serves as an excellent scaffold to accumulate bioactive molecules from hPL such as PDGF-BB, fibronectin (Fn), and α-2 antiplasmin. The NF20 coating shows both fast and a sustained release of the attached bioactive molecules (Fn, VEGF, FGF). The dressing significantly increases the viability of human saphenous vein endothelial cells (HSVECs) cultivated on a collagen-based wound model. The exogenous addition of FGF and VEGF during the coating procedure further increases the HSVECs viability. In addition, the presence of α-2 antiplasmin significantly stabilizes the fibrin mesh and prevents its cleavage by plasmin.
The NF20 coating supplemented with FGF and VEGF provides a promising wound dressing for the complex treatment of DU. The incorporation of various bioactive molecules from hPL and growth factors has great potential to support the healing processes by providing appropriate stimuli in the chronic wound.
糖尿病溃疡(DU)的形成是糖尿病患者常见的并发症,导致严重的慢性伤口。因此,迫切需要对此问题进行综合治疗。本研究探讨了一种生物活性伤口敷料,即由聚(L-丙交酯-共-ε-己内酯)和聚(ε-己内酯)(PLCL/PCL)的可生物降解电纺纳米纤维混合物组成的生物活性伤口敷料,其表面覆盖有一层薄的纤维蛋白层,用于持续输送生物活性分子。
将电纺 PLCL/PCL 纳米纤维用通过控制技术制备的纤维蛋白涂层进行涂覆,并与人类血小板裂解物(hPL)、成纤维细胞生长因子 2(FGF)和血管内皮生长因子(VEGF)一起进行富集。通过扫描电子显微镜和荧光显微镜对涂层进行了表征。评估了蛋白质含量及其释放率以及对人隐静脉内皮细胞(HSVEC)的影响。
通过涂覆含有 20%v/v hPL(NF20)的纤维蛋白网,可获得最高的蛋白质含量。纤维蛋白涂层是从 hPL 中积累 PDGF-BB、纤维连接蛋白(Fn)和α-2 抗纤溶酶等生物活性分子的绝佳支架。NF20 涂层表现出快速且持续释放附着的生物活性分子(Fn、VEGF、FGF)的能力。敷料显著增加了在基于胶原蛋白的伤口模型上培养的人隐静脉内皮细胞(HSVEC)的活力。在涂层过程中外加 FGF 和 VEGF 进一步增加了 HSVEC 的活力。此外,α-2 抗纤溶酶的存在显著稳定了纤维蛋白网并防止其被纤溶酶裂解。
补充有 FGF 和 VEGF 的 NF20 涂层为 DU 的综合治疗提供了一种很有前途的伤口敷料。从 hPL 中掺入各种生物活性分子和生长因子具有很大的潜力,通过在慢性伤口中提供适当的刺激来支持愈合过程。