Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain.

Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo.

Simultaneous concentration and detection of biomarkers on paper.

The lateral-flow immunoassay (LFA) is an inexpensive point-of-care (POC) paper-based diagnostic device with the potential to rapidly detect disease biomarkers in resource-poor settings. Although LFA is inexpensive, easy to use, and requires no laboratory equipment, it is limited by its sensitivity, which remains inferior to that of gold standard laboratory-based assays. Our group is the only one to have previously utilized various aqueous two-phase systems (ATPSs) to enhance LFA detection. In those studies, the sample was concentrated by an ATPS in a test tube and could only be applied to LFA after it had been extracted manually. Here, we bypass the extraction step by seamlessly integrating a polyethylene glycol-potassium phosphate ATPS with downstream LFA detection in a simple, inexpensive, power-free, and portable all-in-one diagnostic device. We discovered a new phenomenon in which the target biomarkers simultaneously concentrate as the ATPS solution flows through the paper membranes, and our device features a 3-D paper well that was designed to exploit this phenomenon. Studies with this device, which were performed at room temperature in under 25 min, demonstrated a 10-fold improvement in the detection limit of a model protein, transferrin. Our next-generation LFA technology is rapid, affordable, easy-to-use, and can be applied to existing LFA products, thereby providing a new platform for revolutionizing the current state of disease diagnosis in resource-poor settings.