Bridges implanted into the injured spinal cord function to stabilize the injury, while also supporting and directing axon growth. The architecture of the bridge is critical to its function, with pores to support cell infiltration that integrates the implant with the host and channels to direct axon elongation. Here, we developed a sucrose fiber template to create poly(lactide-co-glycolide) multiple channel bridges for implantation into a lateral hemisection that had a 3-fold increase in channel number relative to previous bridges and an overall porosity ranging from approximately 70% to 90%. Following implantation into rat and mouse models, axons were observed within channels for all conditions. The axon density within the bridge increased nearly 7-fold relative to previous bridges with fewer channels. Furthermore, increasing the bridge porosity substantially increased the number of axons, which correlated with the extent of cell infiltration throughout the bridge. Analysis of these cell types identified an increased presence of mature oligodendrocytes within the bridge at higher porosities. These results demonstrate that channels and bridge porosity influence the re-growth of axons through the injury. These bridges provide a platform technology capable of being combined with the delivery of regenerative factors for the ultimate goal of achieving functional recovery.
Recombinant methods have been used to engineer artificial protein triblock polymers composed of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed CEC, which bears an impaired C domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation. The negative control CEC does not exhibit binding to small molecule and is inelastic at lower temperatures, affirming the favorable role of C domain and its helical conformation. While both CEC and CEC assemble into micelles, CEC is more densely packed with C domains on the surface enabling the development of networks leading to hydrogel formation. Such protein engineered triblock copolymers capable of forming robust hydrogels hold tremendous promise for biomedical applications in drug delivery and tissue engineering.
1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide
(EDC) is a commonly
used reagent for bioconjugation and peptide synthesis. Both EDC and
the corresponding urea derivative, 1-(3-dimethylaminopropyl)-3-ethylurea
(EDU), are achiral. As the reagent is active in aqueous solutions,
it is a common choice for the study of evolving secondary structural
changes via circular dichroism. This work highlights the effect of
EDU on spectropolarimetric measurements, namely, the problematic absorption
profile at low wavelengths (190–220 nm). We demonstrate that
EDU is capable of erroneously indicating structural changes, particularly
loss of α-helical character, through masking of the characteristic
minimum at 208 nm. However, if the concentrations of the EDU in the
sample are known, then this effect can be anticipated and calculations
of secondary structure can be adjusted to avoid the impacted wavelengths.
Impacts of EDU in a sample are compared to those of standard urea,
which, by contrast, is commonly used as a denaturant in circular dichroism
studies without issue.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.