Cell compatible encapsulation of filaments into 3D hydrogels

Abstract

Tissue engineering scaffolds for nerve regeneration, or artificial nerve conduits, are particularly challenging due to the high level of complexity the structure of the nerve presents. The list of requirements for artificial nerve conduits is long and includes the ability to physically guide nerve growth using physical and chemical cues as well as electrical stimulation. Combining these characteristics into a conduit, while maintaining biocompatibility and biodegradability, has not been satisfactorily achieved by currently employed fabrication techniques. Here we present a method combining pultrusion and wet-spinning techniques facilitating incorporation of pre-formed filaments into ionically crosslinkable hydrogels. This new biofabrication technique allows the incorporation of conducting or drug-laden filaments, controlled guidance channels and living cells into hydrogels, creating new improved conduit designs.

Culture models produced via biomanufacturing for neural tissue-like constructs based on primary neural and neural stem cells

“…In addition, 3D printable graphene composites, with a majority of graphene and a minority of polylactide-co-glycolide particles, greatly support the growth of stem cells as they are ideal extracellular supporting graft [6]. Ionically cross-linkable hydrogels with filaments are fabricated for neurite growth guidance by combining the following techniques: pultrusion and wet-spinning [7]. A suitable mechanical modulus is another engineered advantage and contributes to the long-term stability of tissue constructs.…”

3D Hybrid Small Scale Devices

“…Microfabrication technology enables engineering of micro–nano structures, high throughput, and scalable processes but heretofore required temperature, pressure, and solvents that are not compatible with cells. Microfabrication processes that are cell‐compatible are creating new vistas for 3D integrated nanobiotechnology in science and medicine …”

Tissue engineering with gellan gum

“…4B). This bio-ink has been applied for the patterning of single cell arrays for lipidomics 127 and for the placement of cells within wet-spun alginate fibers 128 . Applying these GG microgels alongside the delivery of bulk scaffolding materials may present a means of forming complex and highresolution tissue structures.…”

“…Meier et al created similar poly-ion complex fibers between GG and amyloid protein nanofibers, reporting the bio-fibers to have high strength, and potential for use in drug release and cell scaffolding 141 . Finally, Schirmer et al recently applied GG microgels to deliver cells in defined channels within wet-spun alginate fibers 128 . Although this study, and others 138 , apply alginate as the primary hydrogel material, the similarity in the rheological and cross-linking behaviours of alginate and GG suggests that these wet-spinning techniques could be applied for the formation of GG fibers as well.…”

“…This bio-ink has been applied for the patterning of single cell arrays for lipidomics 127 and for the placement of cells within wet-spun alginate fibers. 128 Applying these GG microgels alongside the delivery of bulk scaffolding materials may present a means of forming complex and high-resolution tissue structures. Another bioprinting technique applied in the patterning of GG is reactive extrusion printing, whereby GG is delivered simultaneously with Ca 2+ ions.…”