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Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration

机译:可光交联的层粘连蛋白官能化聚乙二醇水凝胶用于椎间盘再生

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摘要

Intervertebral disc (IVD) disorders and age-related degeneration are believed to contribute to lower back pain. There is significant interest in cell-based strategies for regenerating the nucleus pulposus (NP) region of the disc; however, few scaffolds have been evaluated for their ability to promote or maintain an immature NP cell phenotype. Previous studies have shown that NP cell-laminin interactions promote cell adhesion and biosynthesis, which suggests a laminin-functionalized biomaterial may be useful for promoting or maintaining the NP cell phenotype. Here, a photocrosslinkable poly(ethylene glycol)-laminin 111 (PEG-LM111) hydrogel was developed. The mechanical properties of PEG-LM111 hydrogel could be tuned within the range of dynamic shear moduli values previously reported for human NP. When primary immature porcine NP cells were seeded onto PEG-LM111 hydrogels of varying stiffnesses, LM111-presenting hydrogels were found to promote cell clustering and increased levels of sGAG production as compared to stiffer LM111-presenting and PEG-only gels. When cells were encapsulated in 3-D gels, hydrogel formulation was found to influence NP cell metabolism and expression of proposed NP phenotypic markers, with higher expression of N-cadherin and cytokeratin 8 observed for cells cultured in softer (<1 kPa) PEG-LM111 hydrogels. Overall, these findings suggest that soft, LM111-functionalized hydrogels may promote or maintain the expression of specific markers characteristic of an immature NP cell phenotype.
机译:椎间盘(IVD)疾病和与年龄有关的变性被认为是导致下背部疼痛的原因。人们对基于细胞的椎间盘髓核(NP)区域再生策略非常感兴趣。然而,很少有人评估其促进或维持不成熟NP细胞表型的能力。先前的研究表明,NP细胞-层粘连蛋白的相互作用促进细胞粘附和生物合成,这表明层粘连蛋白功能化的生物材料可能对促进或维持NP细胞表型有用。在这里,开发了可光交联的聚(乙二醇)-laminin 111(PEG-LM111)水凝胶。 PEG-LM111水凝胶的机械性能可以在先前针对人类NP报道的动态剪切模量值范围内进行调整。当将原始的未成熟猪NP细胞接种到不同刚度的PEG-LM111水凝胶上时,与较硬的LM111表达和仅PEG凝胶相比,发现LM111表达的水凝胶可促进细胞聚集和sGAG产生水平的提高。当将细胞封装在3-D凝胶中时,发现水凝胶制剂会影响NP细胞的代谢和拟议的NP表型标记的表达,在较软的(<1 kPa)PEG-细胞中培养的细胞中N-钙粘蛋白和细胞角蛋白8的表达更高。 LM111水凝胶。总体而言,这些发现表明,柔软的LM111功能化水凝胶可促进或维持未成熟NP细胞表型特有标志物的表达。

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