Department of Health Technology, Center for Intestinal Absorption and Transport of Biopharmaceuticals , Technical University of Denmark , 2800 Kgs. Lyngby , Denmark.
Department of Health Science and Technology, Laboratory for Stem Cell Research , Aalborg University , Fredrik Bajers Vej 3B , 9220 , Aalborg , Denmark.
ACS Appl Mater Interfaces. 2019 Apr 3;11(13):12283-12297. doi: 10.1021/acsami.9b00154. Epub 2019 Mar 22.
The emergence of nontoxic, eco-friendly, and biocompatible polymers derived from natural sources has added a new and exciting dimension to the development of low-cost and scalable biomaterials for tissue engineering applications. Here, we have developed a mechanically strong and durable hydrogel composed of an eco-friendly biopolymer that exists within the cell walls of fruits and plants. Its trade name is pectin, and it bears many similarities with natural polysaccharides in the native extracellular matrix. Specifically, we have employed a new pathway to transform pectin into a ultraviolet (UV)-cross-linkable pectin methacrylate (PEMA) polymer. To endow this hydrogel matrix with cell differentiation and cell spreading properties, we have also incorporated thiolated gelatin into the system. Notably, we were able to fine-tune the compressive modulus of this hydrogel in the range ∼0.5 to ∼24 kPa: advantageously, our results demonstrated that the hydrogels can support growth and viability for a wide range of three-dimensionally (3D) encapsulated cells that include muscle progenitor (C2C12), neural progenitor (PC12), and human mesenchymal stem cells (hMSCs). Our results also indicate that PEMA-gelatin-encapsulated hMSCs can facilitate the formation of bonelike apatite after 5 weeks in culture. Finally, we have demonstrated that PEMA-gelatin can yield micropatterned cell-laden 3D constructs through UV light-assisted lithography. The simplicity, scalability, processability, tunability, bioactivity, and low-cost features of this new hydrogel system highlight its potential as a stem cell carrier that is capable of bridging the gap between clinic and laboratory.
从天然来源衍生出的无毒、环保且生物相容的聚合物的出现,为组织工程应用中低成本和可扩展生物材料的发展增添了新的令人兴奋的维度。在这里,我们开发了一种由存在于水果和植物细胞壁中的环保生物聚合物组成的机械强度高且耐用的水凝胶。它的商品名为果胶,与天然细胞外基质中的天然多糖有许多相似之处。具体来说,我们采用了一种新途径将果胶转化为可紫外光(UV)交联的果胶甲基丙烯酯(PEMA)聚合物。为了使这种水凝胶基质具有细胞分化和细胞扩展特性,我们还将巯基化明胶纳入了该系统。值得注意的是,我们能够将这种水凝胶的压缩模量精细地调节在 0.5 到 24 kPa 的范围内:有利的是,我们的结果表明,水凝胶可以支持包括肌肉祖细胞(C2C12)、神经祖细胞(PC12)和人骨髓间充质干细胞(hMSC)在内的各种三维(3D)包封细胞的生长和活力。我们的结果还表明,PEMA-明胶包封的 hMSC 可以在培养 5 周后促进类骨质磷灰石的形成。最后,我们证明了 PEMA-明胶可以通过紫外光辅助光刻技术生成具有微图案的细胞负载 3D 结构。这种新水凝胶系统的简单性、可扩展性、可加工性、可调性、生物活性和低成本特点突出了其作为干细胞载体的潜力,能够弥合临床和实验室之间的差距。