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揭示核壳微球的壳亲水性作为生物刺激剂对成纤维细胞生物活性的作用。

Unraveling the role of shell hydrophilicity of core-shell microspheres on fibroblast cell bioactivity as biostimulators.

作者信息

Li Guizhen, Li Xingyang, Xiong Jia, Zeng Haoran, Chen Junfang, Wang Yunong, Guo Liwei, Zhong Wenwei

机构信息

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangzhou Vanxx Bioworks Co., Ltd, Guangzhou 511455, China.

Sustainable Energy and Environment Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China.

出版信息

Int J Pharm. 2025 Aug 20;681:125815. doi: 10.1016/j.ijpharm.2025.125815. Epub 2025 Jun 4.

DOI:10.1016/j.ijpharm.2025.125815
PMID:40480296
Abstract

Core-shell microspheres have shown great potential in the field of biomedical applications, especially in drug delivery, tissue repair, and regenerative medicines, due to their dual properties and multifunctionality. Although the benefits of core-shell microspheres have been advocated in many applications, the role of core-shell microspheres composed of materials of different natures as implants has not been revealed, especially in the interaction between hydrophobic polycaprolactone and hydrophilic alginate materials with fibroblasts cells. This study successfully prepared core-shell microsphere structures of PCL@Alg with hydrophobic outer shell wrapped on a hydrophilic inner core and Alg@PCL with hydrophilic outer shell wrapped on a hydrophobic inner core structure. PCL@Alg The microspheres treated group showed highest cell viability (172.85 %), and highest wound closure rate, reaching 58.34 %. The hydrophilic outer layer of Alg@PCL promoted aligned cell growth around the shell where a dense layer of cells was found surrounding the hydrophilic alginate shell after 24 h incubation. The ELISA results suggested that PCL@Alg microspheres significantly promoted COX-2 production (233.32 pg/mL), while IL-6 levels were the lowest among all treatment groups (17.36 pg/mL). In addition, PCL@Alg microspheres have a significant promoting effect on the synthesis of COL-III (92.25 ng/mL) and COL-I (32.85 ng/mL) as compared to porous PCL microsphere (PMN). The core-shell microsphere wiith hydrophobic PCL shell benefit the production of collagen at accelerated cell growth and migration rate while the inflammation level was remained low. These findings could inspire design application of core-shell microsphere with particular shell thickness for future consideration, paving the way for core-shell microspheres as regenerative treatments for dermal fibroblasts in a safer manner.

摘要

核壳微球由于其双重性质和多功能性,在生物医学应用领域,尤其是药物递送、组织修复和再生医学方面展现出了巨大潜力。尽管核壳微球在许多应用中都备受推崇,但其作为由不同性质材料组成的植入物的作用尚未明确,特别是疏水性聚己内酯和亲水性海藻酸盐材料与成纤维细胞之间的相互作用。本研究成功制备了具有疏水外壳包裹亲水内核的PCL@Alg核壳微球结构以及具有亲水外壳包裹疏水内核结构的Alg@PCL。PCL@Alg微球处理组显示出最高的细胞活力(172.85%)和最高的伤口闭合率,达到58.34%。Alg@PCL的亲水外层促进了细胞在壳周围的定向生长,孵育24小时后,在亲水海藻酸盐壳周围发现了一层密集的细胞层。ELISA结果表明,PCL@Alg微球显著促进了COX - 2的产生(233.32 pg/mL),而IL - 6水平在所有处理组中最低(17.36 pg/mL)。此外,与多孔聚己内酯微球(PMN)相比,PCL@Alg微球对COL - III(92.25 ng/mL)和COL - I(32.85 ng/mL)的合成具有显著促进作用。具有疏水PCL壳的核壳微球在加速细胞生长和迁移速率的同时有利于胶原蛋白的产生,而炎症水平保持较低。这些发现可能会启发未来对具有特定壳厚度的核壳微球设计应用的考虑,为核壳微球以更安全的方式用于真皮成纤维细胞的再生治疗铺平道路。

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