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Co-culture Model for Cutaneous Wound Healing to Assess a Porous Fiber-Based Drug Delivery System.
Tissue Engineering, Part C: Methods ( IF 2.7 ) Pub Date : 2020-09-17 , DOI: 10.1089/ten.tec.2020.0145
Eva Dohle 1 , Andreas Scherrieble 2 , Michael Doser 2 , Sarah Al-Maawi 1 , Martin Hoss 2 , Martin Dauner 2 , Robert Sader 1 , Charles James Kirkpatrick 1 , Shahram Ghanaati 1
Affiliation  

In vitro tissue-engineered cell culture models are an essential instrument to investigate physiological and pathophysiological wound healing mechanisms and to evaluate new beneficial wound dressing materials and therapeutics to identify possible drug targets and to improve regeneration processes in nonhealing and chronic wounds. In this study, the authors established an in vitro model for cutaneous wound healing, based on primary human dermal microvascular endothelial cells (HDMEC) and primary human dermal fibroblasts (HDF) to study wound healing-associated processes. Co-cultivation of HDMEC and HDF results in the formation of microvessel-like structures in long-term co-cultures. The proposed in vitro co-culture model can be easily modified by adding macrophages to simulate the process of inflammation, thus allowing in vitro investigation of pathophysiological wound healing processes present in nonhealing wounds. Furthermore, the beneficial in vitro wound healing model was used to evaluate a porous fiber-based drug delivery dressing material consisting of melt-spun porous fibers that were filled with a hydrogel carrier (gellan gum) containing vascular endothelial growth factor (VEGF). Angiogenic capability was chosen as functional parameter for improved wound healing, and release of deposited VEGF from the dressing material was evaluated up to 7 days of cultivation. The experiments demonstrated that the porous fiber-based drug delivery dressing material for dermal wound healing with incorporated VEGF strongly enhances the process of angiogenesis in the in vitro co-culture model through a release of VEGF over 7 days of cultivation. In conclusion, tissue-engineered human skin equivalents could contribute significantly to the understanding and improvement of drug releasing dressing materials in the context of treating chronic wounds.

中文翻译:

用于评估基于多孔纤维的药物递送系统的皮肤伤口愈合的共培养模型。

体外组织工程细胞培养模型是研究生理和病理生理伤口愈合机制以及评估新的有益伤口敷料和治疗方法以识别可能的药物靶标并改善不愈合和慢性伤口的再生过程的重要工具。在这项研究中,作者基于原代人真皮微血管内皮细胞 (HDMEC) 和原代人真皮成纤维细胞 (HDF)建立了皮肤伤口愈合的体外模型,以研究伤口愈合相关过程。HDMEC 和 HDF 的共同培养导致在长期共同培养中形成微血管样结构。建议的体外通过添加巨噬细胞来模拟炎症过程,可以轻松修改共培养模型,从而允许对不愈合伤口中存在的病理生理伤口愈合过程进行体外研究。此外,有益的体外伤口愈合模型用于评估基于多孔纤维的药物递送敷料材料,该材料由熔纺多孔纤维组成,其中填充有含有血管内皮生长因子 (VEGF) 的水凝胶载体(结冷胶)。选择血管生成能力作为改善伤口愈合的功能参数,并且评估了长达 7 天的培养从敷料材料中释放沉积的 VEGF。实验表明,掺入VEGF的用于皮肤伤口愈合的多孔纤维基药物递送敷料材料在体外强烈增强血管生成过程。通过在培养 7 天后释放 VEGF 来构建共​​培养模型。总之,组织工程人体皮肤等效物可以在治疗慢性伤口的背景下对理解和改进药物释放敷料材料做出重大贡献。
更新日期:2020-09-20
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