A 4-Gene Signature of CDKN1, FDXR,SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.     

Collective Organization Behaviors of Multi-Cell Systems Induced by Engineered ECM-Cell Mechanical Coupling

Cells in vivo are surrounded by fibrous extracellular matrix (ECM), which can mediate the propagation of active cellular forces through stressed fiber bundles and regulate various biological processes. However, the mechanisms for multi-cellular organization and collective dynamics induced by cell-ECM mechanical couplings, which are crucial for the development of novel ECM-based biomaterial for cell manipulation and biomechanical applications, remain poorly understood. Herein, the authors design an in vitro quasi-3D experimental system and demonstrate a transition between spreading and aggregating in collective organizational behaviors of discrete multi-cellular systems, induced by engineered ECM-cell mechanical coupling, with the observed phenomena and underlying mechanisms differing fundamentally from those of cell monolayers. During the process of collective cell organization, the collagen substrate undergoes reconstruction into a dense fiber network structure, which is correlated with local cellular density and consistent with observed enhanced cells' motility; and the weakening of fiber bundle formation within the hydrogel reduces cells’ movement. Moreover, cells can respond to the curvature and shape of the original cell population and form different aggregation patterns. These results elucidate important physical factors involved in collective cell organization and provide important references for potential applications of biomaterials in new therapies and tissue engineering.     

Radiation-curable prepreg composites

Advanced composites, specifically carbon-fiber-reinforced epoxies, are used extensively for a variety of demanding structural applications, primarily because of their high strength-to-weight and stiffness-to-weight ratios, corrosion resistance, and damage tolerance characteristics. Electron beam (EB) treatment can be used to produce useful physical and/or chemical changes in plastics and composites by initiating various polymerization and crosslinking reactions. The advantages of using EB rather than thermal curing for carbon-fiber-reinforced epoxy composites include curing at ambient temperature, reduced curing times, and fewer volatiles. An EB-curable carbon fiber-acrylated epoxy composite is being developed for various applications. The tensile properties of the 14-ply EB-cured epoxy laminate were comparable with the properties of the thermally cured laminates used in the aircraft industry. Research is continuing to develop resin formulations and select coupling agents to improve the compression properties of EB-cured laminates.     

Low Energy Blue Pulsed Light-Activated Injectable Materials for Restoring Thinning Corneas

Many alternatives to human donor corneas are being developed to meet the global shortage of donated tissues. However, corneal transplantation remains the gold standard for diseases resulting in thinning corneas. In this study, transparent low energy photoactivated extracellular matrix-mimicking materials are developed for intrastromal injection to restore stromal thickness. The injectable biomaterials are comprised of short peptides and glycosaminoglycans (chondroitin, hyaluronic acid) that assemble into a hydrogel when pulsed with low-energy blue light. The dosage of pulsed-blue light needed for material activation is minimal at 8.5 mW cm⁻², thus circumventing any blue light cytotoxicity. Intrastromal injection of these light-activated biomaterials in rat corneas shows that two iterations of the formulations remain stable in situ without stimulating significant inflammation or neovascularization. The use of low light intensities and the ability of the developed materials to stably rebuild and change the curvature of the cornea tissue make these formulations attractive for clinical translation.