Sphingosine-1-phosphate (S1P), a bioactive lipid, is a potent candidate for treatment of ischemic vascular disease. However, designing biomaterial systems for the controlled release of S1P to achieve therapeutic angiogenesis presents both biological and engineering challenges. Thus, the objective of this study was to design a hydrogel system that provides controlled and sustained release of S1P to establish local concentration gradients that promote neovascularization. Alginate hydrogels have been extensively studied and characterized for delivery of proangiogenic factors. We sought to explore if chitosan (0, 0.1, 0.5, or 1%) incorporation could be used as a means to control S1P release from alginate hydrogels. With increasing chitosan incorporation, hydrogels exhibited significantly denser pore structure and stiffer material properties. While 0.1 and 0.5% chitosan gels demonstrated slower respective release of S1P, release from 1% chitosan gels was similar to alginate gels alone. Furthermore, 0.5% chitosan gels induced greater sprouting and directed migration of outgrowth endothelial cells (OECs) in response to released S1P under hypoxia in vitro. Overall, this report presents a platform for a novel alginate-chitosan hydrogel of controlled composition and in situ gelation properties that can be used to control lipid release for therapeutic applications.
Gene therapy is a promising strategy for musculoskeletal tissue repair and regeneration where local and sustained expression of proteins and/or therapeutic nucleic acids can be achieved. However, the musculoskeletal tissues present unique engineering and biological challenges as recipients of genetic vectors. Targeting specific cell populations, regulating expression in vivo, and overcoming the harsh environment of damaged tissue accompany the general concerns of safety and efficacy common to all applications of gene therapy. In this review, we will first summarize these challenges and then discuss how biomaterial carriers for genetic vectors can address these issues. Second, we will review how limitations specific to given vectors further motivate the utility of biomaterial carriers. Finally, we will discuss how these concepts have been combined with tissue engineering strategies and approaches to improve the delivery of these vectors for musculoskeletal tissue regeneration.
Microgels fabricated through distinct microfluidic procedures encapsulate and release functioning lentivectors in a controlled manner.Please check this proof carefully. Our staff will not read it in detail after you have returned it.Translation errors between word-processor files and typesetting systems can occur so the whole proof needs to be read. Please pay particular attention to: tabulated material; equations; numerical data; figures and graphics; and references. If you have not already indicated the corresponding author(s) please mark their name(s) with an asterisk. Please e-mail a list of corrections or the PDF with electronic notes attached -do not change the text within the PDF file or send a revised manuscript. Corrections at this stage should be minor and not involve extensive changes. All corrections must be sent at the same time.Please bear in mind that minor layout improvements, e.g. in line breaking, table widths and graphic placement, are routinely applied to the final version.Please note that, in the typefaces we use, an italic vee looks like this: n, and a Greek nu looks like this: n.We will publish articles on the web as soon as possible after receiving your corrections; no late corrections will be made.Please return your final corrections, where possible within 48 hours of receipt, by e-mail to: materialsB@rsc.orgQueries for the attention of the authors However, achieving safe, localized, and sufficient gene expression remain key challenges for effective lentivectoral therapy. Localized and efficient gene expression can be promoted by developing material systems to deliver lentivectors. Here, we address the utility of microgel encapsulation as a strategy for the controlled release of lentivectors. Three distinct routes for ionotropic gelation of alginate were incorporated into microfluidic templating to create lentivector-loaded microgels. Comparisons of the three microgels revealed marked differences in mechanical properties, crosslinking environment, and ultimately lentivector release and functional gene expression in vitro. Gelation with chelated calcium demonstrated low utility for gene delivery due to a loss of lentivector function with acidic gelation conditions. Both calcium carbonate gelation, and calcium chloride gelation, preserved lentivector function with a more sustained transduction and gene expression over 4 days observed with calcium chloride gelated microgels. The validation of these two strategies for lentivector microencapsulation may provide a platform for controlled gene delivery.
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