Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability.
Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability.
复制标题
控制自动产生的组织等效物（板岩）的3D结构，以优化角膜移植物组成和稳定性。
DOI：
10.1016/j.biomaterials.2016.12.023
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发表时间：
2017-03
期刊：
影响因子：
14
通讯作者：
Connon CJ
中科院分区：
文献类型：
--
作者：
Gouveia RM;González-Andrades E;Cardona JC;González-Gallardo C;Ionescu AM;Garzon I;Alaminos M;González-Andrades M;Connon CJ
理想情况下，被设计成在体内发挥特定物理和生理作用的生物材料应该包括类似于它们打算取代的天然组织的组件和微结构。为此，可植入的生物材料需要仔细设计，以具有正确的结构和组成属性，从而赋予其生物功能。在这项研究中，我们证明了可以自下而上地定义对这些特性的控制，使用智能表面模板来调节人类可移植组织的结构、组成和生物力学。使用具有不同各向异性的多功能多肽两亲性涂层表面，我们能够控制角膜基质细胞的表型，并指导它们制造接近模仿人类角膜天然基质板层的自举组织。然后详细评估由这些角膜基质自举类似组织等价物(石板)组成的细胞外基质的类型和排列，并表明其与组织功能相关。具体地说，与含有随机取向成分的石板相比，含有排列整齐的胶原纤维的石板明显更厚、更致密，更耐蛋白质降解。此外，石板是高度透明的，同时增加了对近紫外线辐射的吸收。重要的是，角膜基质石板能够构成具有更高层次复杂性的组织，要么通过堆积产生更厚的组织，要么作为基质支持完全分化的复层角膜上皮。石板作为兔角膜模型的植入物也被认为是安全的，能够与周围的宿主组织整合，在9个月的随访中不会引发炎症、新生血管或任何其他排斥迹象。因此，这项工作为从头开始生物制造易于取回的、无支架的人体组织铺平了道路，该组织具有受控的结构、成分和功能特性，以取代角膜和其他组织。
Ideally, biomaterials designed to play specific physical and physiological roles in vivo should comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.