Uncultured adipose-derived regenerative cells (ADRCs) seeded in collagen scaffold improves dermal regeneration, enhancing early vascularization and structural organization following thermal burns
Uncultured adipose-derived regenerative cells (ADRCs) seeded in collagen scaffold improves dermal regeneration, enhancing early vascularization and structural organization following thermal burns
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DOI：
10.1016/j.burns.2015.05.004
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发表时间：
2015-11-01
期刊：
影响因子：
2.7
通讯作者：
Fraser, John K.
中科院分区：
文献类型：
--
作者：
Foubert, Philippe;Barillas, Samuel;Fraser, John K.
目的：组织工程学的发展已经产生了一系列用于烧伤创面愈合的天然和合成皮肤替代物。组织工程皮肤替代物的长期生存能力需要新血管的形成和成熟，以优化植入后的存活和生物整合。许多研究已经证明了脂肪来源的再生细胞（ADRC）促进血管生成和调节炎症的能力。在此基础上，假设将ADRC添加到基于胶原的基质（CBM）（即Integra）中将增强在急性热烧伤的情况下组织良好的伤口组织的形成和成熟。本研究的目的是评估是否接种未培养的ADRCs到CBM将改善基质性能和提高愈合的移植wound.Methods：全厚度热烧伤创建8哥廷根小型猪的背部。损伤后两天，对伤口进行筋膜切除，并将动物随机接受接种有未培养的ADRC或对照载体的Integra。通过数字化伤口成像、组织病理学和免疫组化分析进行伤口愈合评估。结果：体外分析表明，新鲜分离的ADRCs在CBM上粘附并增殖。组织学评分显示，与载剂的CBM相比，接受载ADRC的CBM的伤口中伤口床组织的加速成熟。这与创床组织深度和胶原沉积的显著增加有关（p < 0.05）。在第14天和第21天，接受ADRC负载的CBM的伤口中的伤口床中的血管密度比接受载剂负载的CBM的伤口中的血管密度高50%至69：6%（p = 0.05）。此外，与CBM一起递送的ADRC在第21天显示血管腔面积增加和血管成熟（p = 0.05）。有趣的是，与单独的CBM相比，在接受ADRC加载的支架的动物中，CBM内的血管分布和总体细胞结构增加了50%和45%（p < 0.05）。(C)2015 Elsevier Ltd和ISBI。All rights reserved.
Objective: Advances in tissue engineering have yielded a range of both natural and synthetic skin substitutes for burn wound healing application. Long-term viability of tissue-engineered skin substitutes requires the formation and maturation of neo-vessels to optimize survival and biointegration after implantation. A number of studies have demonstrated the capacity of Adipose Derived Regenerative Cells (ADRCs) to promote angiogenesis and modulate inflammation. On this basis, it was hypothesized that adding ADRCs to a collagen-based matrix (CBM) (i.e. Integra) would enhance formation and maturation of well-organized wound tissue in the setting of acute thermal burns. The purpose of this study was to evaluate whether seeding uncultured ADRCs onto CBM would improve matrix properties and enhance healing of the grafted wound.Methods: Full thickness thermal burns were created on the backs of 8 Gottingen mini-swine. Two days post-injury wounds underwent fascial excision and animals were randomized to receive either Integra seeded with either uncultured ADRCs or control vehicle. Wound healing assessment was performed by digital wound imaging, histopathological and immunohistochemical analyses.Results: In vitro analysis demonstrated that freshly isolated ADRCs adhered and propagated on the CBM. Histological scoring revealed accelerated maturation of wound bed tissue in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM. This was associated with a significant increase in depth of the wound bed tissue and collagen deposition (p < 0.05). Blood vessel density in the wound bed was 50% to 69:6% greater in wounds receiving ADRCs-loaded CBM compared to vehicle-loaded CBM (p = 0.05) at day 14 and 21. In addition, ADRCs delivered with CBM showed increased blood vessel lumen area and blood vessel maturation at day 21(p = 0.05). Interestingly, vascularity and overall cellularity within the CBM were 50% and 45% greater in animals receiving ADRC loaded scaffolds compared to CBM alone (p < 0.05).Conclusions: These data demonstrate that seeding uncultured ADRCs onto CBM dermal substitute enhances wound angiogenesis, blood vessel maturation and matrix remodeling. (C) 2015 Elsevier Ltd and ISBI. All rights reserved.