Design of a novel wound dressing consisting of alginate hydrogel and simvastatin-incorporated mesoporous hydroxyapatite microspheres for cutaneous wound healing
Design of a novel wound dressing consisting of alginate hydrogel and simvastatin-incorporated mesoporous hydroxyapatite microspheres for cutaneous wound healing
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DOI：
10.1039/c6ra20892d
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发表时间：
2016-11
期刊：
影响因子：
3.9
通讯作者：
Weiling Yu;Yingying Jiang;Tuan-Wei Sun;C. Qi;Huakun Zhao;Feng Chen;Zhongmin Shi;Ying-Jie Zhu;Daoyun Chen;Yaohua He
中科院分区：
文献类型：
--
作者：
Weiling Yu;Yingying Jiang;Tuan-Wei Sun;C. Qi;Huakun Zhao;Feng Chen;Zhongmin Shi;Ying-Jie Zhu;Daoyun Chen;Yaohua He
具有促血管生成活性的伤口敷料对于全层皮肤伤口的快速愈合是期望的。辛伐他汀除了具有降脂作用外，还具有促进血管生成的作用。然而，含有辛伐他汀的水凝胶基伤口敷料的构造由于其水不溶性而仍然是一个挑战。在本研究中，一种新型的伤口敷料组成的海藻酸钠水凝胶（AH）和辛伐他汀纳入介孔羟基磷灰石微球（S-MHMs）的辛伐他汀的药物缓释。我们首先研究了辛伐他汀对人脐静脉内皮细胞（HUVECs）血管生成分化的影响。体外实验结果显示，辛伐他汀能显著促进HUVECs的迁移和管腔形成。此外，辛伐他汀可激活Akt和Erk信号通路，LY 294002和PD 98059可逆转Akt和Erk信号通路的激活，提示Akt和Erk信号通路均参与了辛伐他汀诱导的血管生成过程。此外，辛伐他汀可显著上调缺氧诱导因子-1 α（HIF-1α）和血管内皮生长因子（VEGF）的表达，这两种因子在血管生成中起重要作用。在体内实验中，辛伐他汀被纳入介孔羟基磷灰石微球（MHMs）合成使用果糖1，6-二磷酸三钠盐（FBP）作为磷源，通过微波辅助水热法。将辛伐他汀负载的MHMs（S-MHMs）掺入藻酸盐水凝胶（S-MHMs/AH）制备为伤口敷料以促进全层皮肤伤口愈合。结果表明，S-MHMs/AH显著促进新血管形成，并加速皮肤伤口的上皮再生。本研究表明，S-MHMs/AH复合材料作为一种新型的伤口愈合敷料的潜在应用。
Wound dressings with pro-angiogenic activity are desirable for the rapid healing of full-thickness cutaneous wounds. It is well accepted that simvastatin can stimulate angiogenesis in addition to its lipid-lowering efficacy. However, the construction of a hydrogel-based wound dressing containing simvastatin remains a challenge due to its water-insolubility. In the present study, a novel wound dressing composed of alginate hydrogel (AH) and simvastatin-incorporated mesoporous hydroxyapatite microspheres (S-MHMs) was constructed for the sustained drug release of simvastatin. We first investigated the effect of simvastatin on the angiogenic differentiation of human umbilical vein endothelial cells (HUVECs). The in vitro results revealed that simvastatin significantly promoted the migration and tube formation of HUVECs. Furthermore, the activation of the Akt and Erk signaling pathways was detected in HUVECs upon treatment with simvastatin, and enhanced tube formation was reversed by LY294002 and PD98059, which indicated that both the Akt and Erk signaling pathways were involved in the process of angiogenesis induced by simvastatin. Moreover, simvastatin significantly up-regulated the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), which play essential roles in angiogenesis. For the in vivo experiments, simvastatin was incorporated into mesoporous hydroxyapatite microspheres (MHMs) synthesized using fructose 1,6-bisphosphate trisodium salt (FBP) as the phosphorous source by the microwave-assisted hydrothermal method. An simvastatin-loaded MHMs (S-MHMs) incorporated alginate hydrogel (S-MHMs/AH) was prepared as a wound dressing to promote the full-thickness cutaneous wound healing. The results demonstrated that S-MHMs/AH significantly enhanced new blood vessel formation and accelerated the reepithelialization of the cutaneous wounds. The present study suggests the potential application of the S-MHMs/AH composite as a novel dressing for wound healing.