Solid freeform fabrication of designer scaffolds of hyaluronic acid for nerve tissue engineering

Abstract

The field of tissue engineering and regenerative medicine will tremendously benefit from the development of three dimensional scaffolds with defined micro- and macro-architecture that replicate the geometry and chemical composition of native tissues. The current report describes a freeform fabrication technique that permits the development of nerve regeneration scaffolds with precisely engineered architecture that mimics that of native nerve, using the native extracellular matrix component hyaluronic acid (HA). To demonstrate the flexibility of the fabrication system, scaffolds exhibiting different geometries with varying pore shapes, sizes and controlled degradability were fabricated in a layer-by-layer fashion. To promote cell adhesion, scaffolds were covalently functionalized with laminin. This approach offers tremendous spatio-temporal flexibility to create architecturally complex structures such as scaffolds with branched tubes to mimic branched nerves at a plexus. We further demonstrate the ability to create bidirectional gradients within the microfabricated nerve conduits. We believe that combining the biological properties of HA with precise three dimensional micro-architecture could offer a useful platform for the development of a wide range of bioartificial organs.

Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture

“…Compared to the raster scanning of nozzle based 3D printers, DLP based 3D printers are capable to continuously project and alter entire planes of photo-masks to fabricate 3D objects without artificial interfaces, which provides better mechanical integrity [18,20]. More importantly, since the printing is based on the photopolymerization of a solution, a wide range of biomaterials as well as cells, nanoparticles, and biomolecules can be incorporated into the printed tissue constructs [21–24]. …”

A 3D Tissue-Printing Approach for Validation of Diffusion Tensor Imaging in Skeletal Muscle

“…This technique has recently developed to fabricate various functional materials and devices [28][29][30] and tissue engineering scaffolds. [31][32][33] Therefore, DLP-based 3D printing is an attractive technique to fabricate anisotropic phantoms with skeletal muscle geometry for DT-MRI. The focus of this study is to use new 3D printing strategies to develop a novel set of precision-engineered phantoms for characterizing the interrelationship between microstructural variables and MR-diffusion parameters in skeletal muscle.…”

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

“…Recently, microstereolithography was used for patterning NGCs with intricate geometries, and a 3D printing methodology was also applied to construct anatomical nerve regeneration pathways based on 3D scanning of a rat bifurcating nerve141819. However, to our knowledge, the fabrication of a NGC based on patient-specific anatomy has never been explored.…”

“…GelMA has suitable biological properties and tunable physical characteristics, and thus has been widely used for biomedical applications, such as engineering of bone, cartilage, and vascular tissues1013. The gelatin derivative is an inherently cell-adhesive material comprised of modified natural extracellular matrix (ECM) components that can provide functional cues to the resident cells within the scaffolds and thus can aid in nerve regeneration1415. Moreover, cell delivery can be facilitated by priming the support cells in vitro before transplanted into the injury site, which reduces the rate of cell loss and leakage to surrounding tissues1115.…”

“…However, challenges remain for conventional manufacturing methodologies to fabricate nerve conduits with complex or custom geometries, because the conduits are mainly manufactured around cylindrical substrates. The acquired nerve conduits with simpler architectures may not be sufficient to promote structural and functional nerve regeneration141819. Recent advances in materials and manufacturing enable the fabrication of complex or patient-specific devices20.…”