Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction
Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction
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DOI：
10.1126/scitranslmed.aau6210
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发表时间：
2019-05-01
影响因子：
17.1
通讯作者：
Mao, Hai-Quan
中科院分区：
文献类型：
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作者：
Li, Xiaowei;Cho, Brian;Mao, Hai-Quan
由于肿瘤切除、创伤、衰老和先天性畸形造成的软组织损失每年影响数百万人。现有的软组织修复方案有几个缺点：手术方案，如使用自体组织瓣，导致供体部位缺损，假体植入物容易发生异物反应，导致纤维化，脂肪移植和真皮填充物仅限于小体积缺损，只能提供短暂的体积修复。此外，大体积脂肪移植和其他组织工程的尝试受到血管向内生长不良的阻碍。目前，没有现成的材料可以填充软组织缺损中损失的体积，同时促进早期血管生成。在这里，我们报告了一种纳米纤维-水凝胶复合材料，解决了这些问题。通过将电纺聚（ε-己内酯）纤维和透明质酸水凝胶网络之间的界面结合，我们产生了一种复合材料，模仿软组织细胞外基质的微结构和机械性能。在大鼠模型中皮下注射后，该复合物允许宿主巨噬细胞浸润并将其调节成促再生表型。通过分泌促血管生成的细胞因子和生长因子，这些极化的巨噬细胞能够逐渐重塑和用血管化的软组织替换复合材料。这种宿主细胞浸润和血管生成也观察到在兔模型修复软组织缺损填充的复合材料。这种可注射的纳米纤维-水凝胶复合材料增强了天然组织的再生反应，从而实现了持久的软组织修复效果。
Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(epsilon-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.