Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications

Biologically and mechanically driven design of an RGD-mimetic macroporous foam for adipose tissue engineering applications
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DOI:
10.1016/j.biomaterials.2016.07.004
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发表时间:
2016-10-01
期刊:
影响因子:
14
通讯作者:
Lenardi, Cristina
Lenardi, Cristina
中科院分区:
工程技术1区
文献类型:
--
作者:
Rossi, Eleonora;Gerges, Irini;Lenardi, Cristina

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尽管脂肪组织缺损的临床治疗,特别是乳房组织重建,具有一定程度的功效,但许多缺点仍然影响新形成的脂肪组织的长期存活。为了克服这个问题,在过去的几十年里,在脂肪组织工程领域中已经研究了几种支架材料。然而,一个策略,能够概括一个合适的环境,脂肪组织重建和维护仍然缺失。为了解决这一需求,我们采用了生物和机械驱动的设计,以制造用于脂肪组织重建的RGD模拟聚(酰胺胺)低聚物大孔泡沫(OPAAF)。该支架的设计满足三个基本标准:诱导细胞粘附和增殖的能力,支持体内血管化和天然组织机械性能的匹配。通过自由基聚合和发泡反应,将聚酰胺-胺低聚物制成具有分级孔隙率的软质支架。OPAAF的特点是高吸水能力,渐进降解动力学和理想的脂肪组织重建的机械性能。使用上皮细胞、成纤维细胞和内皮细胞(分别为MDCK、3 T3 L1和HUVEC)在体外评估OPAAF支持细胞粘附、增殖和脂肪生成的能力。此外,在小鼠模型中的体内皮下植入突出了OPAAF支持脂肪生成和血管浸润的潜力。总体而言,报告的结果支持使用OPAAF作为工程化脂肪组织构建体的支架。(C)2016爱思唯尔有限公司版权所有。
Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing. To address this need, we adopted a biologically and mechanically driven design to fabricate an RGD-mimetic poly(amidoamine) oligomer macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. Poly(amidoamine) oligomers were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. OPAAF's ability to support cell adhesion, proliferation and adipogenesis was assessed in vitro using epithelial, fibroblast and endothelial cells (MDCK, 3T3L1 and HUVEC respectively). In addition, in vivo subcutaneous implantation in murine model highlighted OPAAF potential to support both adipogenesis and vessels infiltration. Overall, the reported results support the use of OPAAF as a scaffold for engineered adipose tissue construct. (C) 2016 Elsevier Ltd. All rights reserved.