Tailoring the biofunctionality of collagen biomaterials via tropoelastin incorporation and EDC-crosslinking.
Tailoring the biofunctionality of collagen biomaterials via tropoelastin incorporation and EDC-crosslinking.
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DOI：
10.1016/j.actbio.2021.08.027
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发表时间：
2021-08
影响因子：
9.7
通讯作者：
D. Bax;Malavika Nair;A. Weiss;R. Farndale;S. Best;R. Cameron
中科院分区：
文献类型：
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作者：
D. Bax;Malavika Nair;A. Weiss;R. Farndale;S. Best;R. Cameron
重建几乎所有组织的细胞生态位需要由多种细胞外基质（ECM）大分子制成的复合材料。由于其广泛的组织分布、物理属性和纯度，胶原蛋白和最近的原弹性蛋白代表了生物材料开发中两种有吸引力的 ECM 成分。在这里，我们将原弹性蛋白和胶原蛋白混合，利用每种生物分子的细胞调节特性。原弹性蛋白稳定地共混到胶原生物材料中，并在 EDC 交联后保留。我们发现人真皮成纤维细胞 (HDF)、大鼠神经胶质细胞 (Rugli) 和 HT1080 纤维肉瘤细胞分别通过 EDTA 敏感和 EDTA 不敏感受体与弹性蛋白原连接或不与弹性蛋白原连接。这些不同的弹性蛋白结合特性使我们能够探测细胞对原弹性蛋白-胶原蛋白复合材料的反应，从而为复合材料的胶原蛋白和原弹性蛋白成分赋予特定的生物活性。除了胶原蛋白之外，原弹性蛋白还增加了总 Rugli 细胞的粘附、扩散和增殖。这种现象在原弹性蛋白-胶原复合材料的 EDC 交联中持续存在。添加原弹性蛋白不影响总 HDF 和 HT1080 细胞粘附；然而，它增加了独立于阳离子的粘附的贡献，而不影响细胞形态，或者对于 HT1080 细胞来说，不影响增殖。相反，EDC 交联决定了 HDF 和 HT1080 细胞反应。这些数据表明原弹性蛋白成分主导具有非整联蛋白原弹性蛋白受体的细胞的反应。当非整合素原弹性蛋白受体对细胞活性并不重要时，胶原蛋白成分的 EDC 修饰可指导细胞功能。使用这种方法，我们分配了原弹性蛋白-胶原复合材料的每个成分的生物学贡献，从而允许通过更生理相关的机制对定向细胞功能进行明智的生物材料设计。重要性声明由多个细胞外基质（ECM）大分子制成的生物材料需要完全重建每个ECM大分子与其中接合的天然组织生态位 细胞表面受体的特定库。在这里，我们研究了弹性蛋白原与胶原蛋白的结合，因为它们通过不同的受体与细胞相互作用。我们鉴定了特定的细胞系，它们通过不同类别的细胞表面受体与弹性蛋白原结合。这些表明，当弹性蛋白原与胶原蛋白结合时，会以受体使用依赖性方式改变细胞行为。整合素介导的弹性蛋白原相互作用影响细胞增殖，非整合素受体影响细胞扩散和增殖。这些数据揭示了生物材料大分子组成、细胞表面受体和细胞行为之间的相互作用，推进定制材料设计并为特定细胞群提供功能。
Recreating the cell niche of virtually all tissues requires composite materials fabricated from multiple extracellular matrix (ECM) macromolecules. Due to their wide tissue distribution, physical attributes and purity, collagen, and more recently, tropoelastin, represent two appealing ECM components for biomaterials development. Here we blend tropoelastin and collagen, harnessing the cell-modulatory properties of each biomolecule. Tropoelastin was stably co-blended into collagen biomaterials and was retained after EDC-crosslinking. We found that human dermal fibroblasts (HDF), rat glial cells (Rugli) and HT1080 fibrosarcoma cells ligate to tropoelastin via EDTA-sensitive and EDTA-insensitive receptors or do not ligate with tropoelastin, respectively. These differing elastin-binding properties allowed us to probe the cellular response to the tropoelastin-collagen composites assigning specific bioactivity to the collagen and tropoelastin component of the composite material. Tropoelastin addition to collagen increased total Rugli cell adhesion, spreading and proliferation. This persisted with EDC-crosslinking of the tropoelastin-collagen composite. Tropoelastin addition did not affect total HDF and HT1080 cell adhesion; however, it increased the contribution of cation-independent adhesion, without affecting the cell morphology or, for HT1080 cells, proliferation. Instead, EDC-crosslinking dictated the HDF and HT1080 cellular response. These data show that a tropoelastin component dominates the response of cells that possess non-integrin based tropoelastin receptors. EDC modification of the collagen component directs cell function when non-integrin tropoelastin receptors are not crucial for cell activity. Using this approach, we have assigned the biological contribution of each component of tropoelastin-collagen composites, allowing informed biomaterial design for directed cell function via more physiologically relevant mechanisms.Statement of significanceBiomaterials fabricated from multiple extracellular matrix (ECM) macromolecules are required to fully recreate the native tissue niche where each ECM macromolecule engages with a specific repertoire of cell-surface receptors. Here we investigate combining tropoelastin with collagen as they interact with cells via different receptors. We identified specific cell lines, which associate with tropoelastin via distinct classes of cell-surface receptor. These showed that tropoelastin, when combined with collagen, altered the cell behaviour in a receptor-usage dependent manner. Integrin-mediated tropoelastin interactions influenced cell proliferation and non-integrin receptors influenced cell spreading and proliferation. These data shed light on the interplay between biomaterial macromolecular composition, cell surface receptors and cell behaviour, advancing bespoke materials design and providing functionality to specific cell populations.