The characterization of hyaluronic acid and polyethylene glycol hydrogels for neural tissue engineering.

摘要

Neural tissue engineering through the use of biomaterials holds great promise for treating a wide variety of neurological disorders. The customizable nature of hydrogels provides the opportunity to mimic the brain's unique extracellular matrix (ECM). Hydrogels can be used to recreate this ECM environment to support neural cells in vitro, through 3D culturing, or during transplantation procedures. To be effective, hydrogels must be characterized chemically, physically, and mechanically, and the biocompatibility of these materials with neural cells and brain tissue must be defined. Twenty-five hydrogels were created from ratios of hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Hydrogels were assessed for the properties of polymerization, degradation, and compressive modulus, and the cytocompatibility with encapsulated neural progenitor cells (NPC) from fetal and adult sources. The physical and mechanical properties of the hydrogels were found to be dependent on the polymer concentration. Additionally, the compressive moduli of the hydrogels were comparable to rodent brain tissue, indicating that the hydrogel formulations developed were physiologically relevant. Subsequently, NPC derived from fetal and adult rats (fNPC and aNPC, respectively) were encapsulated within the hydrogels. Twenty-four hour cell survival was highest at lower concentrations of HA and PEG. Three-week fNPC and aNPC differentiation was demonstrated to be influenced by mechanical properties. Fetal-NPC generally produced greater numbers of astrocytes in stiffer hydrogels, while increased numbers of neurons were observed in softer hydrogels. Greater numbers of aNPC became neuronal, regardless of stiffness. When two chosen hydrogels were used to implant NPC into the brain, the results suggested that encapsulated NPC survived at up to 50% two months post-implantation, indicating good cytocompatibility. Further, the implanted cells were able to migrate from the hydrogel into the surrounding brain tissue farther than unencapsulated cells. Immunolabeling for glial cells demonstrated that the hydrogels elicited a similar immune response as control treatments, establishing the histocompatibility with brain tissue. Based on these studies, HA-PEG hydrogels were biocompatible and could be used therapeutically in the brain. Further modifications and specializations of these hydrogels, such as the inclusion of growth factors or attachment factors, may provide specific therapeutic support for encapsulated cells and/or neurodegenerative disorders.