Combining electrospun nanofibers with cell-encapsulating hydrogel fibers for neural tissue engineering.

A promising component of biomaterial constructs for neural tissue engineering are electrospun fibers, which differentiate stem cells and neurons as well as direct neurite growth. However, means of protecting neurons, glia, and stem cells seeded on electrospun fibers between lab and surgical suite have yet to be developed. Here we report an effort to accomplish this using cell-encapsulating hydrogel fibers made by interfacial polyelectrolyte complexation (IPC). IPC-hydrogel fibers were created by interfacing acid-soluble chitosan (AsC) and cell-containing alginate and spinning them on bundles of aligned electrospun fibers. Primary spinal astrocytes, cortical neurons, or L929 fibroblasts were mixed into alginate hydrogels prior to IPC-fiber spinning. The viability of each cell type was assessed at 30 min, 4 h, 1 d, and 7 d after encapsulation in IPC hydrogels. Some neurons were encapsulated in IPC-hydrogel fibers made from water-soluble chitosan (WsC). Neurons were also stained with Tuj1 and assessed for neurite extension. Neuron survival in AsC-fibers was worse than astrocytes in AsC-fibers (p < 0.05) and neurons in WsC-fibers (p < 0.05). As expected, neuron and glia survival was worse than L929 fibroblasts (p < 0.05). Neurons in IPC-hydrogel fibers fabricated with WsC extended neurites robustly, while none in AsC fibers did. Neurons remaining inside IPC-hydrogel fibers extended neurites inside them, while others de-encapsulated, extending neurites on electrospun fibers, which did not fully integrate with IPC-hydrogel fibers. This study demonstrates that primary neurons and astrocytes can be encapsulated in IPC-hydrogel fibers at good percentages of survival. IPC hydrogel technology may be a useful tool for encapsulating neural and other cells on electrospun fiber scaffolds.

Mechanical tension applied to substrate films specifies location of neuritogenesis and promotes major neurite growth at the expense of minor neurite development.

One obstacle in neural repair is facilitating axon growth long enough to reach denervated targets. Recent studies show that axonal growth is accelerated by applying tension to bundles of neurites, and additional studies show that mechanical tension is critical to all neurite growth. However, no studies yet describe how individual neurons respond to tensile forces applied to cell bodies and neurites simultaneously; neither do any test motor neurons, a phenotype critical to neural repair. Here we examine the growth of dissociated motor neurons on stretchable substrates. E15 spinal motor neurons were cultured on poly-lactide-co-glycolide films stretched at 4.8, 9.6, or 14.3 mm day(-1). Morphological analysis revealed that substrate stretching has profound effects on developing motor neurons. Stretching increases major neurite length; it also forces neuritogenesis to occur nearest poles of the cell closest to the sources of tension. Stretching also reduces the number of neurites per neuron. These data show that substrate stretching affects neuronal morphology by specifying locations on the cell where neuritogenesis occurs and favoring major neurite growth at the expense of minor neurites. These results serve as a building block for development of new techniques to control and improve the growth of neurons for nerve repair purposes.

A systematic review of interventions for reducing HIV risk behaviors among people living with HIV in the United States, 1988-2012.

OBJECTIVE: To conduct a systematic review to examine interventions for reducing HIV risk behaviors among people living with HIV (PLWH) in the United States. METHODS: Systematic searches included electronic databases from 1988 to 2012, hand searches of journals, reference lists of articles, and HIV/AIDS Internet listservs. Each eligible study was evaluated against the established criteria on study design, implementation, analysis, and strength of findings to assess the risk of bias and intervention effects. RESULTS: Forty-eight studies were evaluated. Fourteen studies (29%) with both low risk of bias and significant positive intervention effects in reducing HIV transmission risk behaviors were classified as evidence-based interventions (EBIs). Thirty-four studies were classified as non-EBIs due to high risk of bias or nonsignificant positive intervention effects. EBIs varied in delivery from brief prevention messages to intensive multisession interventions. The key components of EBIs included addressing HIV risk reduction behaviors, motivation for behavioral change, misconception about HIV, and issues related to mental health, medication adherence, and HIV transmission risk behavior. CONCLUSION: Moving evidence-based prevention for PLWH into practice is an important step in making a greater impact on the HIV epidemic. Efficacious EBIs can serve as model programs for providers in healthcare and nonhealthcare settings looking to implement evidence-based HIV prevention. Clinics and public health agencies at the state, local, and federal levels can use the results of this review as a resource when making decisions that meet the needs of PLWH to achieve the greatest impact on the HIV epidemic.