No abstract

The regenerative capacity of the peripheral nervous system is closely related to the role that Schwann cells (SCs) play in construction of the basement membrane containing multiple extracellular matrix proteins and secretion of neurotrophic factors, including laminin (LN) and brain-derived neurotrophic factor (BDNF). Here, we developed a self-assembling peptide (SAP) nanofiber hydrogel based on self-assembling backbone Ac-(RADA) 4 -NH 2 (RAD) dual-functionalized with laminin-derived motif IKVAV (IKV) and a BDNF-mimetic peptide epitope RGIDKRHWNSQ (RGI) for peripheral nerve regeneration, with the hydrogel providing a three-dimensional (3D) microenvironment for SCs and neurites. Methods: Circular dichroism (CD), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were used to characterize the secondary structures, microscopic structures, and morphologies of self-assembling nanofiber hydrogels. Then the SC adhesion, myelination and neurotrophin secretion were evaluated on the hydrogels. Finally, the SAP hydrogels were injected into hollow chitosan tubes to bridge a 10-mm-long sciatic nerve defect in rats, and in vivo gene expression at 1 week, axonal regeneration, target muscular re-innervation, and functional recovery at 12 weeks were assessed. Results: The bioactive peptide motifs were covalently linked to the C-terminal of the self-assembling peptide and the functionalized peptides could form well-defined nanofibrous hydrogels capable of providing a 3D microenvironment similar to native extracellular matrix. SCs displayed improved cell adhesion on hydrogels with both IKV and RGI, accompanied by increased cell spreading and elongation relative to other groups. RSCs cultured on hydrogels with IKV and RGI showed enhanced gene expression of NGF, BDNF, CNTF, PMP22 and NRP2, and decreased gene expression of NCAM compared with those cultured on other three groups after a 7-day incubation. Additionally, the secretion of NGF, BDNF, and CNTF of RSCs was significantly improved on dual-functionalized peptide hydrogels after 3 days. At 1 week after implantation, the expressions of neurotrophin and myelin-related genes in the nerve grafts in SAP and Autograft groups were higher than that in Hollow group, and the expression of S100 in groups containing both IKV and RGI was significantly higher than that in groups containing either IKV or RGI hydrogels, suggesting enhanced SC proliferation. The morphometric parameters of the regenerated nerves, their electrophysiological performance, the innervated muscle weight and remodeling of muscle fibers, and motor function showed that RAD/IKV/RGI and RAD/IKV-GG-RGI hydrogels could markedly improve axonal regeneration with enhanced re-myelination and motor functional recovery through the synergetic effect of IKV and RGI functional motifs. Conclusions: We found that the dual-functionalized SAP hydrogels promoted RSC adhesion, my...

Novel gemini supra-amphiphiles, [Mim-4-Mim][DBS](2) and [Mim-4-Mim][DS](2), were facilely constructed. A slight variation of building blocks can effectively modulate the driving forces for the fabrication of gemini supra-amphiphiles, thus leading to the fine control of subsequent self-assemblies. [Mim-4-Mim][DS](2), constructed via electrostatic attraction, tends to form micelles and hexagonal liquid crystals. Rich lamellar structures, including unilamellar and multilamellar vesicles, planar bilayers, and lamellar liquid crystals can be formed by [Mim-4-Mim][DBS](2), which is constructed through electrostatic and π-π stacking interactions. With increasing temperatures, [Mim-4-Mim][DBS](2) exhibits interesting phase separation in the L(a) phase, behaving like common nonionic surfactants. The cross-linking between vesicles, where the "bola-type" [Mim-4-Mim](2+) cations act as the bridges, was found to promote the elongation of aggregates until the occurrence of phase separation.

In this paper, low-complexity joint power assignment algorithms are developed for multi-source multi-destination relay networks where multiple sources share a common relay that forwards all received signals simultaneously to destinations. In particular, we consider the following power optimization strategies: (i) Minimization of the total transmission power of the sources and the relay under the constraint that the signal-to-interference-plus-noise ratio (SINR) requirement of each source-destination pair is satisfied, and (ii) Maximization of the minimum SINR among all source-destination pairs subject to any given total power budget. Both optimization problems involve K power variables, where K is the number of source-destination pairs in the network, and an exhaustive search is prohibitive for large K. In this work, we develop a methodology that allows us to obtain an asymptotically tight approximation of the SINR and reformulate the original optimization problems to single-variable optimization problems, which can be easily solved by numerical search of the single variable. Then, the corresponding optimal transmission power at each source and relay can be calculated directly. The proposed optimization schemes are scalable and lead to power assignment algorithms that exhibit the same optimization complexity for any number (K) of source-destination pairs in the network. Moreover, we apply the methodology that we developed to solve a related max-min SINR based optimization problem in which we determine power assignment for the sources and the relay to maximize the minimum SINR among all source-destination pairs subject to any given total power budget. Extensive numerical studies illustrate and validate our theoretical developments.Index Terms-Cooperative networks, interference relay channels, max-min SINR optimization, multi-source multi-destination relay networks, optimum power allocation.