Cartilage Tissue Engineering by Extrusion Bioprinting: Process Analysis, Risk Evaluation, and Mitigation Strategies

Abstract

Extrusion bioprinting is considered promising in cartilage tissue engineering since it allows the fabrication of complex, customized, and living constructs potentially suitable for clinical applications. However, clinical translation is often complicated by the variability and unknown/unsolved issues related to this technology. The aim of this study was to perform a risk analysis on a research process, consisting in the bioprinting of a stem cell-laden collagen bioink to fabricate constructs with cartilage-like properties. The method utilized was the Failure Mode and Effect Analysis/Failure Mode and Effect Criticality Analysis (FMEA/FMECA) which foresees a mapping of the process to proactively identify related risks and the mitigation actions. This proactive risk analysis allowed the identification of forty-seven possible failure modes, deriving from seventy-one potential causes. Twenty-four failure modes displayed a high-risk level according to the selected evaluation criteria and threshold (RPN > 100). The results highlighted that the main process risks are a relatively low fidelity of the fabricated structures, unsuitable parameters/material properties, the death of encapsulated cells due to the shear stress generated along the nozzle by mechanical extrusion, and possible biological contamination phenomena. The main mitigation actions involved personnel training and the implementation of dedicated procedures, system calibration, printing conditions check, and, most importantly, a thorough knowledge of selected biomaterial and cell properties that could be built either through the provided data/scientific literature or their preliminary assessment through dedicated experimental optimization phase. To conclude, highlighting issues in the early research phase and putting in place all the required actions to mitigate risks will make easier to develop a standardized process to be quickly translated to clinical use.

3D bioprinting of photo‐crosslinkable silk methacrylate (SilMA)‐polyethylene glycol diacrylate (PEGDA) bioink for cartilage tissue engineering

“…Cell viabilities are subjected to range of properties such as shear stress, rheological properties of bioink, needle gauge, shape of extrusion nozzle, and extrusion mechanism during extrusion bioprinting. In a recent study, chondrogenesis was impeded in extrusion based bioprinting system above a particular shear stress threshold with viscous hydrogels 50 . In this study, SilMA‐PEGDA based bioink was extruded through a nozzle, however; higher chondrocytes viability (>95%) was observed with preservation of chondrocytes phenotype and cartilage matrix deposition.…”

“…In a recent study, chondrogenesis was impeded in extrusion based bioprinting system above a particular shear stress threshold with viscous hydrogels. 50 In this study, SilMA-PEGDA based bioink was extruded through a nozzle, however; higher chondrocytes viability (>95%) was…”

A 3D Collagen-Based Bioprinted Model to Study Osteosarcoma Invasiveness and Drug Response

“…Therefore, by properly tuning the polymerization parameters, we can change the mechanical properties of the scaffolds. In addition, in the design of the pore size, the physical hydrogel long-term swelling behavior and the need for higher porosity values should be considered to guarantee proper nutrient transport properties during culture conditions [ 32 ].…”

Fabrication of 3D-printed quaternary scaffolds containing polymeric matrix plus alginate nanoparticles and MWCNTs for cartilage tissue engineering

“…Among all AM methods, extrusion-based techniques are the best option. This method, which drives biomaterial inks out of a nozzle by applying controlled pressure onto a stage, is considered a promising approach for cartilage tissue engineering applications owing to providing the fabrication of complex, customized, and living substrates with potentially proper aspects for clinical applications [20] [21]. In addition, using the liquid phase extrusion 3D printing method compared to melt extrusion methods did not damage the polymer structure and made it possible to print 4 polymer components.…”