Incorporating β-cyclodextrin into collagen scaffolds to sequester growth factors and modulate mesenchymal stem cell activity.
Incorporating β-cyclodextrin into collagen scaffolds to sequester growth factors and modulate mesenchymal stem cell activity.
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DOI：
10.1016/j.actbio.2018.06.033
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发表时间：
2018-08
影响因子：
9.7
通讯作者：
Harley BAC
中科院分区：
文献类型：
--
作者：
Grier WK;Tiffany AS;Ramsey MD;Harley BAC
用于一系列组织工程应用的生物材料的开发，越来越需要对生物分子信号（如生长因子）的生物利用度进行控制，以促进预期的细胞反应。虽然研究工作主要集中在将生物分子以共价结合或自由扩散的方式掺入多孔的三维生物材料中，但也存在利用瞬时相互作用在预期的时间范围内浓缩生长因子活性的机会。在此，我们报道了将β - 环糊精掺入一种胶原蛋白 - 糖胺聚糖（GAG）模型支架中，作为一种通过主 - 客体相互作用被动隔离和释放生长因子的方法，以控制间充质干细胞的分化。掺入β - 环糊精的胶原蛋白 - 糖胺聚糖支架显示出更好的隔离效果，以及转化生长因子 - β1（TGF - β1）更长时间的保留和释放。我们进一步表明，从β - 环糊精修饰的支架中，TGF - β1和骨形态发生蛋白 - 2（BMP - 2）更长时间的保留和释放足以影响间充质干细胞的代谢活性和增殖，以及与不同的骨软骨分化相关的Smad 2/3和Smad 1/5/8通路的差异激活。此外，基因表达分析表明，从β - 环糊精 - 胶原蛋白 - 糖胺聚糖（β - 环糊精CG）支架中释放的TGF - β1促进了早期软骨特异性分化。最终，这项工作建立了一种通过超分子相互作用在胶原蛋白 - 糖胺聚糖（CG）支架内掺入和展示生长因子的新方法。这样的设计框架为在三维胶原蛋白 - 糖胺聚糖支架内选择性地改变多种生物分子的生物利用度提供了机会，以增强细胞活性，用于一系列肌肉骨骼再生医学应用。
The development of biomaterials for a range of tissue engineering applications increasingly requires control over the bioavailability of biomolecular cues such as growth factors in order to promote desired cell responses. While efforts have predominantly concentrated on covalently-bound or freely-diffusible incorporation of biomolecules in porous, three-dimensional biomaterials, opportunities exist to exploit transient interactions to concentrate growth factor activity over desired time frames. Here, we report the incorporation of β-cyclodextrin into a model collagen-GAG scaffold as a means to exploit the passive sequestration and release of growth factors via guest-host interactions to control mesenchymal stem cell differentiation. Collagen-GAG scaffolds that incorporate β-cyclodextrin show improved sequestration as well as extended retention and release of TGF- β1. We further show extended retention and release of TGF- β1 and BMP-2 from β-cyclodextrin modified scaffolds was sufficient to influence the metabolic activity and proliferation of mesenchymal stem cells as well as differential activation of Smad 2/3 and Smad 1/5/8 pathways associated with differential osteochondral differentiation. Further, gene expression analysis showed TGF-β1 release from β-cyclodextrin CG scaffolds promoted early chondrogenic-specific differentiation. Ultimately, this work establishes a novel method for the incorporation and display of growth factors within CG scaffolds via supramolecular interactions. Such a design framework offers opportunities to selectively alter the bioavailability of multiple biomolecules within a three-dimensional collagen-GAG scaffold to enhance cell activity for a range of musculoskeletal regenerative medicine applications.
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