Abstract
Neural tissue engineering (TE) represents a promising new avenue of therapy to support nerve recovery and regeneration. To recreate the complex environment in which neurons develop and mature, the ideal biomaterials for neural TE require a number of properties and capabilities including the appropriate biochemical and physical cues to adsorb and release specific growth factors. Here, we present neural TE constructs based on electrospun serum albumin (SA) fibrous scaffolds. We doped our SA scaffolds with an iron-containing porphyrin, hemin, to confer conductivity, and then functionalized them with different recombinant proteins and growth factors to ensure cell attachment and proliferation. We demonstrated the potential for these constructs combining topographical, biochemical, and electrical stimuli by testing them with clinically relevant neural populations derived from human induced pluripotent stem cells (hiPSCs). Our scaffolds could support the attachment, proliferation, and neuronal differentiation of hiPSC-derived neural stem cells (NSCs), and were also able to incorporate active growth factors and release them over time, which modified the behavior of cultured cells and substituted the need for growth factor supplementation by media change. Electrical stimulation on the doped SA scaffold positively influenced the maturation of neuronal populations, with neurons exhibiting more branched neurites compared to controls. Through promotion of cell proliferation, differentiation, and neurite branching of hiPSC-derived NSCs, these conductive SA fibrous scaffolds are of broad application in nerve regeneration strategies.
Highlights
Nerve injuries in either the central nervous system (CNS) or peripheral nervous system (PNS) can cause severe neurological deficits, resulting in the diminished physical and psychological well-being of patients.[1,2] As the regenerative ability of the human nervous system is limited, these injuries can be permanent due to the relative shortage of therapeutic options.[2]
We first coated the scaffold for 24 h in a laminin containing solution with a known concentration, and collected the coating solution and evaluated the laminin adsorption using ELISA to determine the amount of remaining laminin in the coating solution after incorporation (Figure 2A)
The results showed a significantly higher amount of remaining laminin in the nondoped Serum albumin (SA) scaffolds, indicating the hemindoped SA scaffolds and the PDL-coated glass slides exhibited more laminin adsorption compared to the nondoped SA scaffolds
Summary
Nerve injuries in either the central nervous system (CNS) or peripheral nervous system (PNS) can cause severe neurological deficits, resulting in the diminished physical and psychological well-being of patients.[1,2] As the regenerative ability of the human nervous system is limited, these injuries can be permanent due to the relative shortage of therapeutic options.[2]. Building a bioengineered construct that mimics neural tissue requires the presence of a scaffold that can provide housing for a supportive extracellular environment along with the physical guidance necessary for nerve repair and neural regeneration.[4,5] A widely used method to construct scaffolds for neural tissue engineering (TE) is electrospinning: this is a simple, potentially large-scale fabrication process capable of generating nano/microscale fibers for 3D scaffold architecture.[6,7] While artificial polymeric scaffolds are widely used, the generation and use of self-derived biomaterials from adults remains to be explored.[8] Serum albumin (SA), which is abundant and can be rapidly replenished in humans or animals, has been widely used in biomedical research for cell culture and storage, in vitro fertilization, and transplantation.[9] As a natural carrier protein with multiple ligand binding sites and the ability to bind different cellular receptors, SA has been exploited as a potential delivery platform for drugs and biomolecules.[10] With its ease of isolation from clinical samples and lowest cost compared to other commercially available proteins, SA has become an attractive autogenic biomaterial for TE with optimal cell compatibility.[8,11,12]
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