Hyaluronic Acid-Functionalized Highly Porous Polymeric Materials for Stem Cell Culture

We describe the synthesis of a functional macroporous polymer material and its potential use as a scaffold to support the 3D culture of hematopoietic stem and progenitor cells (HSPCs). Glycidyl methacrylate (GMA)-based emulsion-templated porous polymers (known as polyHIPEs) were prepared by photopolymerization and subsequently surface functionalized with hyaluronic acid (HA) using Huisgen azide-alkyne cycloaddition click reaction, inferring a high degree of functionalization based on the near-quantitative nature of the reactions. Quantitative azidation of GMA-based polyHIPEs is achieved by the ring opening reaction of epoxide rings with sodium azide. Reductive amination reaction is used to end-cap HA with alkyne functionality to be later clicked onto the azidified polyHIPE surfaces. The synthesized polyHIPE materials are characterized by 1H nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR), Raman and X-ray photoelectron spectroscopy (XPS). Scanning electron microscopy (SEM) and compression testing are also conducted on the polyHIPE scaffolds to evaluate their morphological and mechanical characteristics, respectively. Biocompatibility and cell viability were assessed, along with preliminary stem cell culture experiments to evaluate the suitability of HA-functionalized polyHIPE scaffolds for stem cell maintenance and proliferation. These experiments revealed a notable increase of approximately 20% in CD36+ cell proliferation on HA-polyHIPE scaffolds compared to the control GMA-polyHIPE scaffolds. The multifunctionality served by HA, such as its biocompatibility, biodegradability, nonimmunogenicity, anti-inflammatory properties, antiangiogenic characteristics and binding ability to biological targets critical to mimicking stem cell environment, significantly advances the development of biological scaffolds for tissue engineering and regeneration.