Abstract
To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro.
Highlights
The therapeutic delivery of autologous cells to support the structure and functions of biological tissues is a core paradigm in regenerative medicine
After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules
For most sets of parameters tested, a continuous fiber was extruded (Figure 1b,c) and, more interestingly, in a subset of cases, it was spontaneously assembled in the strainer as a consistent, self-standing fibrous scaffold, as is shown in Figure 1d, where the appearance of wet and dry microfiber patches is shown
Summary
The therapeutic delivery of autologous cells to support the structure and functions of biological tissues is a core paradigm in regenerative medicine. The extrusion method, on the other hand, represents the simplest technique for microfiber formation, and involves the injection of a precursor solution into a gelator solution This fabrication technique is mainly employed to produce continuous single-standing fibers for cell encapsulation [26,28], and mainly relies on the use of sodium alginate and its mild gelation mechanism (room temperature, close to neutral pH) in the presence of divalent cations [29]. Despite its recognized advantages in terms of general biocompatibility and non-immunogenicity, the lack of specific binding sites in alginate for cell adhesion means that it cannot be metabolically dealt with, and the high molecular weight residues are too large for renal clearing For this reason, chemical modification (e.g., oxidation, or RDG coupling) [30] and blending with cell-interactive components are common strategies [23,31,32,33,34]. As the possibility for exploiting this system within different applications relies on the possibility of tuning the chemical composition and properties, blends with common biological macromolecules (gelatin and hyaluronic acid) were processed to patches, to demonstrate the versatility of this fabrication strategy
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