Transcriptomic analysis reveals the immune response of human microglia to a soy protein and collagen hybrid bioscaffold.

Inflammatory reactions resulting from spinal cord injury cause significant secondary damage. Microglial cells activate CD4+ T cells via major histocompatibility complex class II (MHCII) molecules. The activated T cells lead to neural tissue damage and demyelination at early stages of spinal cord injury. Control of the inflammatory response may attenuate the injury process. In this study, we compared gene expression in human microglia grown on soy protein-collagen hybrid scaffolds versus collagen scaffolds. Differentially expressed genes (DEGs) were subjected to gene ontology (GO) and pathway enrichment assays. Among down-regulated genes, the "antigen processing and presentation" pathway shows enrichment, primarily due to the down-regulation of MHCII molecules. The DEGs in this pathway show enrichment of binding sites for several transcription factors, with CIITA and IRF8 being the top candidates. The down-regulation of MHCII along with the significant enrichment of the GO term "focal adhesion" among the up-regulated genes helps explain the higher motility of microglial cells on the hybrid scaffold compared with that on the collagen scaffold. Up-regulated genes associated with "focal adhesion" include DNM2, AHNAK, and HYOU1, which have been previously implicated in increased cell motility. Overall, our study indicates that the use of hybrid scaffolds containing soy protein and collagen may modulate the immune response of wounded neural tissue.

A Protein Composite Neural Scaffold Modulates Astrocyte Migration and Transcriptome Profile.

Bioscaffold implantation is a promising approach to facilitate the repair and regeneration of wounded neural tissue after injury to the spinal cord or peripheral nerves. However, such bioscaffold grafts currently result in only limited functional recovery. The generation of a neural scaffold using a combination of collagen and glutenin is reported. The conduit material and mechanical properties, as well as its effect on astrocyte behavior is tested. After neural injuries, astrocytes move into the lesion and participate in the process of remodeling the micro-architecture of the wounded neural tissue. In this study, human astrocytes grown on glutenin-collagen scaffolds show higher motility and a lower proliferation rate compared with those grown on collagen scaffolds. RNA sequencing reveals that astrocytes grown on the two types of scaffolds show differentially expressed genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as actin cytoskeleton and focal adhesion that regulate astrocyte migration on scaffolds. The gene expression of aggrecan and versican, chondroitin sulfate proteoglycans that inhibit axonal growth, is down-regulated in astrocytes grown on glutenin-collagen scaffolds. These outcomes indicate that the implantation of glutenin-collagen scaffolds may promote astrocyte function in the neural regeneration process by enhanced cell migration and reduced glial scar formation.

Bioscaffold-based study of glioblastoma cell behavior and drug delivery for tumor therapy.

Glioblastoma multiforme (GBM) is a severe form of brain cancer with an average five-year survival rate of 6.7%. Current treatment strategies include surgical resection of the tumor area and lining the lesion site with therapeutics, which offer only a moderate impact on increasing survival rates. Drug-testing models based on the monolayer cell culture method may partially explain the lack of advancement in effective GBM treatment, because this model is limited in its ability to show heterogeneous cell-cell and cell-environment interactions as tumor cells in the in vivo state. The development of bioscaffold-based culture models is an important improvement in GBM research, preclinical trials, and targeted drug testing, through better mimicking of the heterogeneity of tumor environmental conditions. A major hurdle towards better GBM outcomes is in delivering medication across the blood-brain barrier (BBB), which normally prevents the crossing of materials into the treatment site. The delivery of therapeutics using bioscaffolds is a potential means of overcoming the BBB and could potentially facilitate long-lasting drug release. A number of natural and synthetic materials have been studied for their biodegradability, toxicity, distribution, and pharmaceutical stability, which are needed to determine the overall effectiveness and safety of glioblastoma treatment. This review summarizes advancements in the research of bioscaffold-based GBM cell growth systems and the potential of using bioscaffolds as a carrier for drug delivery.