The proliferation of computer-aided design and additive manufacturing enables on-demand fabrication of complex, three-dimensional structures. However, combining the versatility of cell-laden hydrogels within the 3D printing process remains a challenge. Herein, we describe a facile and versatile method that integrates polymer networks (including hydrogels) with 3D-printed mechanical supports to fabricate multicomponent (bio)materials. The approach exploits surface tension to coat fenestrated surfaces with suspended liquid films that can be transformed into solid films. The operating parameters for the process are determined using a physical model, and complex geometric structures are successfully fabricated. We engineer, by tailoring the window geometry, scaffolds with anisotropic mechanical properties that compress longitudinally (~30% strain) without damaging the hydrogel coating. Finally, the process is amenable to high cell density encapsulation and co-culture. Viability (>95%) was maintained 28 days after encapsulation. This general approach can generate biocompatible, macroscale devices with structural integrity and anisotropic mechanical properties.
An
ideal engineered biomaterial for organ repair or tissue replacement
should incorporate a scaffolding structure that recapitulates organ
geometry, physical properties (such as toughness or elasticity), and
possible mechanical anisotropy, as well as a tailored microenvironment
for cells to encourage biologic function and integration with the host1.
The emergence of additive manufacturing, i.e., three-dimensional (3D)
printing, has enabled the design of (bio)materials with high precision,
fine control of architecture, and mechanical properties, as well as
patient-specific geometry informed by advanced biomedical imaging2,3,4.
In parallel, natural and synthetic hydrogels mimicking critical aspects
of the extracellular matrix, have been employed broadly in regenerative
medicine as they integrate well in vivo and can be engineered with a
range of elastic moduli and surface chemistries specific to the cell
type of interest5.
Integrating the full utility of cell-laden hydrogels within the 3D
printing process remains, however, an active challenge. Realization of
the full 3D structure of living tissue with relevant mechanical
properties is particularly difficult.
3D bioprinting has emerged as a means to fabricate geometrically defined and cell-laden biomaterials. Predominant strategies include inkjet bioprinting, microextrusion and laser-assisted bioprinting, and rely on layer-by-layer deposition of hydrogels and cells6,7. Despite significant progress, the hydrogel-based 3D-printed constructs commonly possess insufficient mechanical stability and structural integrity, especially when printing with low modulus materials (E < 100 kPa)6,8. In addition, as the printing is done on a planar surface, the possibility of material shapes and designs is limited and complex mechanical structures are difficult to print. Embedded bioprinting approaches have been developed wherein material is printed directly into a temporary support bath. Examples include a shear-thinning hydrogel or a thermosensitive gelatin microparticle suspension that provides a temporary mechanical support during printing and is removed after crosslinking, enabling omni-directional printing8,9. This technique has enabled the fabrication of elegant and complex soft materials. In other work, polylactic acid or hydrogel-based scaffolds were printed with micron-scale pores and immersed in a coating solution post-fabrication. The coatings improved cell adhesion and bio-integration of the 3D-printed structures10,11. Another advance in 3D bioprinting was the development of multimaterial printers, such as the integrated tissue-organ printer (ITOP), to impart the final constructs with mechanical strength and structural stability. This technology allows for the fabrication of structurally supported, cell-laden tissue constructs through sequential printing of cell-laden hydrogel of defined formulation along with a structural support polymer, such as polycaprolactone (PCL)12. The integration of PCL directly within the printing process enabled the ITOP to form stable and supported bioscaffolds on the human-scale.
Here, we develop a facile and efficient method to fabricate mechanically supported and anisotropic, multicomponent biomaterials, which employs surface tension forces to coat reticulated supports with cell-laden hydrogels. A 3D-printed framework is designed and produced with the desired geometry, structure, and mechanical properties. The reticulated scaffold is then dipped into a liquid hydrogel precursor solution (with or without cells) and wetting forces suspend liquid films across the windows as the material is withdrawn from the solution. The metastable, suspended liquid films are transformed into a stable network or hydrogel via standard crosslinking methods forming a permanent coating on the reticulated mesh. Importantly, the hydrogel coating on the outer surface of the construct enables facile encapsulation of mammalian cells as well as subsequent cell seeding. Mechanically and functionally complex biomaterials are made in this manner without the need to write material directly at every voxel in the final construct. This significantly decreases total fabrication time and minimizes cell handling. Furthermore, the process is versatile in material design and does not rely on any specialized equipment; the method is agnostic with respect to the upstream 3D printer, scaffolding material (e.g., resins, metals, biodegradable polymers), and class of hydrogel. Thus, this approach can potentially expand the regenerative medicine toolkit in a manner that is accessible to most biomedical labs.
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3D bioprinting has emerged as a means to fabricate geometrically defined and cell-laden biomaterials. Predominant strategies include inkjet bioprinting, microextrusion and laser-assisted bioprinting, and rely on layer-by-layer deposition of hydrogels and cells6,7. Despite significant progress, the hydrogel-based 3D-printed constructs commonly possess insufficient mechanical stability and structural integrity, especially when printing with low modulus materials (E < 100 kPa)6,8. In addition, as the printing is done on a planar surface, the possibility of material shapes and designs is limited and complex mechanical structures are difficult to print. Embedded bioprinting approaches have been developed wherein material is printed directly into a temporary support bath. Examples include a shear-thinning hydrogel or a thermosensitive gelatin microparticle suspension that provides a temporary mechanical support during printing and is removed after crosslinking, enabling omni-directional printing8,9. This technique has enabled the fabrication of elegant and complex soft materials. In other work, polylactic acid or hydrogel-based scaffolds were printed with micron-scale pores and immersed in a coating solution post-fabrication. The coatings improved cell adhesion and bio-integration of the 3D-printed structures10,11. Another advance in 3D bioprinting was the development of multimaterial printers, such as the integrated tissue-organ printer (ITOP), to impart the final constructs with mechanical strength and structural stability. This technology allows for the fabrication of structurally supported, cell-laden tissue constructs through sequential printing of cell-laden hydrogel of defined formulation along with a structural support polymer, such as polycaprolactone (PCL)12. The integration of PCL directly within the printing process enabled the ITOP to form stable and supported bioscaffolds on the human-scale.
Here, we develop a facile and efficient method to fabricate mechanically supported and anisotropic, multicomponent biomaterials, which employs surface tension forces to coat reticulated supports with cell-laden hydrogels. A 3D-printed framework is designed and produced with the desired geometry, structure, and mechanical properties. The reticulated scaffold is then dipped into a liquid hydrogel precursor solution (with or without cells) and wetting forces suspend liquid films across the windows as the material is withdrawn from the solution. The metastable, suspended liquid films are transformed into a stable network or hydrogel via standard crosslinking methods forming a permanent coating on the reticulated mesh. Importantly, the hydrogel coating on the outer surface of the construct enables facile encapsulation of mammalian cells as well as subsequent cell seeding. Mechanically and functionally complex biomaterials are made in this manner without the need to write material directly at every voxel in the final construct. This significantly decreases total fabrication time and minimizes cell handling. Furthermore, the process is versatile in material design and does not rely on any specialized equipment; the method is agnostic with respect to the upstream 3D printer, scaffolding material (e.g., resins, metals, biodegradable polymers), and class of hydrogel. Thus, this approach can potentially expand the regenerative medicine toolkit in a manner that is accessible to most biomedical labs.
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