A Plasma-alginate Composite Material Provides Improved Mechanical Support For Stem Cell Growth And Delivery
Nicholas E. Clay, Carissa Villanueva, Nicole Wrice, Andrew C. Kowalczewski, Shanmugasundaram Natesan, Robert J. Christy.
US Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
BACKGROUND Plasma-based products have been utilized in a variety of tissue engineering applications, including soft tissue repair and burn wound healing. Plasma contains soluble fibrinogen, which can be converted into an insoluble fibrin-based gel in the presence of thrombin. Plasma gels can serve as three-dimensional templates to deliver therapeutic cells or as growth factor-laden supplements for tissue regeneration in vivo. Unfortunately, plasma-based materials are often soft and easily deformed, thus limiting their usefulness in harsh clinical settings. Therefore, simpler methods to create sturdier plasma/fibrin-based materials are needed. To this end, we hypothesized that mixing alginate and plasma together will create a plasma-alginate composite (PAC) material with improved mechanical and biological properties. METHODS Plasma and alginate were mixed together to create PAC gels with unique formulations. The stiffness and degradation kinetics of the PAC gels were assessed using rheology and a tissue plasminogen activator (tPA)-based degradation assay, respectively. Stem cells were cultured in the PAC gels for 8 days to assess in vitro cell viability and phenotype. An alginate-free plasma gel was used as a control throughout. RESULTS Our results demonstrated that PAC gels with specific compositions of alginate and plasma were 10-times stiffer than the plasma-only gels. Interestingly, tPA-mediated gel lysis rates were independent of alginate concentration. The stiffer PAC gels enabled stem cell proliferation and maintained cell stemness over 8 days in vitro. The presence of alginate within the PAC gel also helped maintain the gel shape and size in culture. CONCLUSIONS In sum, we envision this PAC gel system will extend the use of plasma-based therapies for tissue engineering and wound healing applications. The improved mechanical properties of the PAC gel system will be useful in demanding clinical settings, such as austere trauma environments or mass casualty scenarios.
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