CASE STUDIES View All
Promotion of Spinal Cord Repair
Customer Says:Biogelx hydrogel is easy to prepare following the company’s protocols. Most importantly, the stiffness of the hydrogel can be tuned to be compatible to that of the central nervous system (CNS) tissue – this is very important for any biomaterial…
Stem Cell Differentiation
Customer Says:“The ability to generate hydrogels over a range of stiffnesses from a single material was a huge advantage for our metabolomics experiments as it allowed us to control stem cell growth and differentiation without the use of different media formulations,…
Improving Cartilage Phenotype from Differentiated Pericytes
Customer Says:“Having a biomaterial system that is able to influence phenotypic expression is hugely desirable as a replacement for chemically-induced differentiation methods, as being able to match the features of tissue produced in vitro to the required structure of the lost…
PUBLICATIONS View All
3D model of a human epiblast reveals BMP4-driven symmetry breaking | Nature Cell Biology
Breaking the anterior–posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro 3D model of human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT sig- nalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.
Epac2 elevation reverses inhibition by chondroitin sulfate proteoglycans in vitro and transforms post-lesion inhibitory environment to promote axonal outgrowth in an ex vivo model of spinal cord injury | The Journal of Neuroscience
Millions of patients suffer from debilitating spinal cord injury (SCI) without effective treatments. Elevating cAMP promotes CNS neuron growth in the presence of growth-inhibiting molecules. cAMP’s effects on neuron growth is partly mediated by Epac, comprising Epac1 and Epac2 – the latter predominantly expresses in postnatal neural tissue. Here, we hypothesized that Epac2 activation would enhance axonal outgrowth after SCI. Using in vitro assays, we demonstrated for the first time that Epac2 activation using a specific soluble agonist (S-220) significantly enhanced neurite outgrowth of postnatal rat cortical neurons and markedly overcame the inhibition by chondroitin sulphate proteoglycans and mature astrocytes on neuron growth. We further investigated the novel potential of Epac2 activation in promoting axonal outgrowth by an ex vivo rat model of SCI mimicking post-SCI environment in vivo and by delivering S-220 via a self-assembling Fmoc-based hydrogel that has suitable properties for SCI repair. We demonstrated that S-220 significantly enhanced axonal outgrowth across the lesion gaps in the organotypic spinal cord slices, compared with controls. Furthermore, we elucidated for the first time that Epac2 activation profoundly modulated the lesion environment by reducing astrocyte/microglial activation and transforming astrocytes into elongated morphology that guided outgrowing axons. Finally, we showed that S-220, when delivered by the gel at 3 weeks after contusion SCI in male adult rats, resulted in significantly better locomotor performance for up to 4 weeks post-treatment. Our data demonstrate a promising therapeutic potential of S-220 in SCI, via beneficial effects on neurons and glia post-injury to facilitate axonal outgrowth.
How some labs put more bio into biomaterials | Nature Methods
Biomaterials researchers straddle disparate worlds as they develop materials to mimic dynamic tissue-based and cellular events and cues. They draw on such fields as materials science, chemistry, physics, nanofabrication, informatics, physiology, cell biology, genomics and immunology1,2,3. Some of this research, and the commercial ventures it inspires, can lead to, for example, enhanced ways to mimic cells and tissue-based processes, improved approaches to tissue regeneration or better modes of delivering drugs into the body. Such applications draw on basic insight about the complex materials–biology interface that is challenging to characterize and for which new assay types are needed. Some biomaterials labs draw those disparate worlds closer by using ‘omics approaches to ‘read out’ a material’s impact on cells and fine-tune the traits of their materials.