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首页> 外文期刊>ACS applied materials & interfaces >Neovascularization Induced by the Hyaluronic Acid-Based Spongy-Like Hydrogels Degradation Products
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Neovascularization Induced by the Hyaluronic Acid-Based Spongy-Like Hydrogels Degradation Products

机译：透明质酸类海绵状水凝胶降解产物诱导的新血管形成

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Neovascularization has been a major challenge in many tissue regeneration strategies. Hyaluronic acid (HA) of 3-25 disaccharides is known to be angiogenic due to its interaction with endothelial cell receptors. This effect has been explored with HA-based structures but a transitory response is observed due to HA burst biodegradation. Herein we developed gellan gum (GG)-HA spongy-like hydrogels from semi-interpenetrating network hydrogels with different HA amounts. Enzymatic degradation was more evident in the GG-HA with high HA amount due to their lower mechanical stability, also resulting from the degradation itself, which facilitated the access of the enzyme to the HA in the bulk. GG-HA spongy-like hydrogels hyaluronidase-mediated degradation lead to the release of HA oligosaccharides of different amounts and sizes in a HA content-dependent manner which promoted in vitro proliferation of human umbilical cord vein endothelial cells (HUVECs) but not their migration. Although no effect was observed in human dermal microvascular endothelial cells (hDMECs) in vitro, the implantation of GG-HA spongy-like hydrogels in an ischemic hind limb mice model promoted neovascularization in a material-dependent manner, consistent with the in vitro degradation profile. Overall, GG-HA spongy-like hydrogels with a sustained release of HA oligomers are valuable options to improve tissue vascularization, a critical issue in several applications in the tissue engineering and regenerative medicine field.
机译：在许多组织再生策略中，新血管形成一直是主要挑战。已知3-25个二糖的透明质酸（HA）具有血管生成作用，因为它与内皮细胞受体相互作用。已经用基于HA的结构探索了这种作用，但是由于HA的生物降解，观察到了短暂的反应。本文中，我们从具有不同HA量的半互穿网络水凝胶中开发了吉兰糖胶（GG）-HA海绵状水凝胶。酶降解在具有高HA量的GG-HA中更明显，这是由于它们的机械稳定性较低，这也是由于降解本身导致的，这促进了酶大量进入HA。 GG-HA海绵样水凝胶透明质酸酶介导的降解导致以HA含量依赖性方式释放不同数量和大小的HA寡糖，从而促进人脐带静脉内皮细胞（HUVEC）的体外增殖，但不促进其迁移。尽管在体外人类真皮微血管内皮细胞（hDMEC）中未观察到任何作用，但将GG-HA海绵状水凝胶植入缺血性后肢小鼠模型中，以材料依赖性方式促进了新血管形成，与体外降解情况一致。总的来说，具有HA低聚物持续释放的GG-HA海绵状水凝胶是改善组织血管化的宝贵选择，这是在组织工程和再生医学领域中若干应用中的关键问题。

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