3D Bioprinting

3D bioprinted scaffolds

3D bioprinting techniques offer the advantage of precisely controlling the microstructure of scaffolds used in tissue engineering and drug delivery. In biofabrication, they typically consist on printing bioinks (composed of natural or synthetic polymers) with cells to produce geometrically controlled engineered tissues.

The viscoelastic properties of the bioink often needs to be adjusted to ensure a good printability, shape fidelity and cell-friendly mechanical environment. Once printed, the final strength of the construct has to resemble the one of the specific application. Due to their soft nature and their geometrical complexity, mechanical characterization of such constructs is often challenging with conventional testing technologies.

3D bioprinting techniques offer the advantage of precisely controlling the microstructure of scaffolds used in tissue engineering and drug delivery. In biofabrication, they typically consist on printing bioinks (composed of natural or synthetic polymers) with cells to produce geometrically controlled engineered tissues.

The viscoelastic properties of the bioink often needs to be adjusted to ensure a good printability, shape fidelity and cell-friendly mechanical environment. Once printed, the final strength of the construct has to resemble the one of the specific application. Due to their soft nature and their geometrical complexity, mechanical characterization of such constructs is often challenging with conventional testing technologies.

We have designed the ElastoSens™ Bio to test the viscoelasticity of both bioinks and 3D bioprinted constructs. Bioinks can be poured directly in the sample holder and tested during gelation and crosslinking under controlled temperature and UV light conditions. Scaffolds can either be introduced or directly printed inside the sample holder to be tested on the ElastoSens™ Bio. The instrument applies gentle vibrations to the sample and measures with no contact its response to the mechanical stimulus. Real time changes in the storage (G’) and loss (G’’) shear modulus of either the bioink or scaffold are measured and displayed.

In this example, 3D scaffolds composed of PEGDA/Laponite gels were bioprinted with different porosities by changing the diameter of the filaments (500 μm, 700 μm and 900 μm) while the spacing was maintained equal. The shear storage modulus (G’) of the scaffolds was obtained using the ElastoSens™ Bio. It clearly appears in the graph that reducing the porosity results in the increase of the overall scaffold elasticity.

3D Bioprinting Results
3D Bioprinting directly into sample holder
The precise evaluation of hydrogels viscoelasticity can accelerate their formulation and the optimization of their functionality. Combined with the power of Soft Matter Analytics™, the ElastoSens™ Bio offers an unprecedented development and control platform for scientists and engineers creating hydrogel-based biosystems or devices.

Related Application Notes

The thermoreversible behavior of some polymers relies on the large conformation changes in response to temperature. They have been investigated for a variety of clinical applications that demand an in situ gelation at physiological temperatures. In addition, these polymers have been widely studied for other biomedical applications such as drug delivery and tissue engineering in which the thermoresponsive behavior needs to be balanced with biocompatibility and degradation kinetics.

3D printing technologies offer the advantage of precisely controlling the microstructure of scaffolds used for tissue engineering applications and drug delivery systems. The macro-mechanical properties of these scaffolds are directly related to their microstructure and both are important parameters for cell behavior and drug release.

Related Scientific Articles

This study introduces two novel smart polymer 3D-printable interpenetrating polymer network (IPN) hydrogel biomaterials for potential applications in traumatic brain injury (TBI). These IPN biomaterials show favorable chemical, mechanical, and morphological properties and can potentially assist in the restoration of neurological function and neural tissue regeneration. The scaffolds were prepared using collagen, elastin, and gelatin methacryloyl, and were crosslinked with Irgacure or Irgacure and Genipin. The biomaterials exhibited thermal stability, amorphous nature, and maintained the peptide secondary structure. With a stiffness suitable for softer tissue engineering applications, the IPN biomaterials resemble the native rat cortex. They supported the growth of PC12 cells and showed antimicrobial properties. However, it was observed that the full IPN was more brittle than the semi IPN, which was contradictory to previous literature findings. Overall, this research contributes to the development of potential biomaterials for TBI applications and 3D printing, paving the way for patient-specific scaffolds in neural treatments.

This study presents a novel 3D bioprinting strategy using a microfluidic printhead to fabricate hydrogel fibrous structures of gelatin methacryloyl (GelMA) with precise control over polymer concentration. The printhead utilizes a coaxial core-sheath flow and a photo-crosslinking system to enable in situ cross-linking of GelMA and the formation of hydrogel filaments. Computational modeling was employed to optimize process parameters and understand the diffusive and fluid dynamic behavior of the coaxial flow. The cytocompatibility of the system was demonstrated by bioprinting cell-laden bioinks containing U87-MG cells. This pipeline, integrating computational modeling with bioprinting, has the potential to be applied to various photo-cross-linkable bioinks for the generation of living tissues with customizable material and cellular characteristics.

Treatment of glioblastoma (GBM), as the most lethal type of brain tumor, still remains a major challenge despite the various therapeutic approaches developed over the recent decades. GBM is considered as one of the most therapy-resistant human tumors. Treatment with temozolomide (TMZ) chemotherapy and radiotherapy in GBM patients has led to 30% of two-year survival rate (American Brain Tumor Association), representing a demanding field to develop more effective therapeutic strategies. This study presents a novel method for local delivery of all-trans retinoic acid (ATRA) for targeting GBM cells as a possible adjuvant therapeutic strategy for this disease. We have used 3D bioprinting to fabricate hydrogel meshes laden with ATRA-loaded polymeric particles. The ATRA-loaded meshes have been shown to facilitate a sustained release of ATRA with tunable release rate. Cell viability assay was used to demonstrate the ability of fabricated meshes in reducing cell growth in U-87 MG cell line. We later showed that the developed meshes induced apoptotic cell death in U-87 MG. Furthermore, the use of hydrogel for embedding the ATRA-loaded particles can facilitate the immobilization of the drug next to the tumor site. Our current innovative approach has shown the potential to open up new avenues for treatment of GBM, benefiting patients who suffer from this debilitating disease.


     

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