Plasma–Alginate Composite Material Provides Improved Mechanical Support for Stem Cell Growth and Delivery

Abstract

Blood plasma-based products have been recently utilized in different tissue engineering applications, ranging from soft tissue repair to bone regeneration. Plasma contains fibrinogen which can be converted to an insoluble fibrin-laden gel in the presence of activated thrombin. In tissue engineering, these plasma-based materials can serve either as a three-dimensional scaffold to deliver therapeutic cells in vivo or as a growth factor-rich supply for tissue regeneration. Unfortunately, plasma-based materials are often mechanically weak and easily deformed, thus limiting their usability in harsh clinical settings. Simpler methods to create sturdier plasma-based materials are therefore needed. To this end, we hypothesized that combining alginate with plasma can create a composite plasma material with improved mechanical properties. Incorporating alginate into plasma produced composite gels with increasing bulk stiffness, as measured by rheology. Specifically, the plasma–alginate composite (PAC) gels with an alginate concentration of 2.86 mg/mL were 10-fold stiffer than pure plasma gels (11 vs 112 Pa). Interestingly, gel lysis rates were unchanged despite increasing alginate concentration (lysis time approximately 50 min). Adipose-derived stem cells cultured in the stiffer PAC gels expressed stemness markers (THY1, ENG, NT5E) at levels comparable to those in the pure plasma gels. Similarly, proangiogenic factor secretion was also constant across all gel conditions. In sum, we envision this PAC gel system will extend the use of plasma gel-based therapies into more rigorous clinical applications.