A 3D-bioprinting exemplar of the consequences of the regulatory requirements on customised processes

Computer-aided three-dimensional (3D) printing approaches to the industrial production of customised 3D functional living constructs for restoration of tissue and organ function face significant regulatory challenges. Using the manufacture of a customised, 3D-bioprinted nasal implant as a well-informed but hypothetical exemplar, we examine how these products might be regulated. Existing EU and US regulatory frameworks do not account for the differences between 3D-printing and conventional manufacturing methods or the ability to create individual customised products using mechanised rather than craft approaches. Already subject to extensive regulatory control, issues related to control of the computer-aided design to manufacture process and the associated software system chain present additional scientific and regulatory challenges for manufacturers of these complex 3D-bioprinted advanced combination products

Review of additive manufactured tissue engineering scaffolds: relationship between geometry and performance

Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to produce scaffolds with intricate porous geometries that were not feasible with traditional manufacturing processes. Researchers can control the structural geometry through a wide range of customisable printing parameters and design choices including material, print path, temperature, and many other process parameters. Currently, the impact of these choices is not fully understood. This review focuses on how the position and orientation of extruded filaments, which sometimes referred to as the print path, lay-down pattern, or simply "scaffold design", affect scaffold properties and biological performance. By analysing trends across multiple studies, new understanding was developed on how filament position affects mechanical properties. Biological performance was also found to be affected by filament position, but a lack of consensus between studies indicates a need for further research and understanding. In most research studies, scaffold design was dictated by capabilities of additive manufacturing software rather than free-form design of structural geometry optimised for biological requirements. There is scope for much greater application of engineering innovation to additive manufacture novel geometries. To achieve this, better understanding of biological requirements is needed to enable the effective specification of ideal scaffold geometries

Design and fabrication of a hybrid alginate hydrogel/poly(ε-caprolactone) mold for auricular cartilage reconstruction

The aim of this study was to design and manufacture an easily assembled cartilage implant model for auricular reconstruction. First, the printing accuracy and mechanical properties of 3D-printed poly-ε-caprolactone (PCL) scaffolds with varying porosities were determined to assess overall material properties. Next, the applicability of alginate as cell carrier for the cartilage implant model was determined. Using the optimal outcomes of both experiments (in terms of (bio)mechanical properties, cell survival, neocartilage formation, and printing accuracy), a hybrid auricular implant model was developed. PCL scaffolds with 600 μm distances between strands exhibited the best mechanical properties and most optimal printing quality for further exploration. In alginate, chondrocytes displayed high cell survival (~83% after 21 days) and produced cartilage-like matrix in vitro. Alginate beads cultured in proliferation medium exhibited slightly higher compressive moduli (6 kPa) compared to beads cultured in chondrogenic medium (3.5 kPa, p >.05). The final auricular mold could be printed with 300 μm pores and high fidelity, and the injected chondrocytes survived the culture period of 21 days. The presented hybrid auricular mold appears to be an adequate model for cartilage tissue engineering and may provide a novel approach to auricular cartilage regeneration for facial reconstruction

Data for VOLCO a predictive model for 3D printed microarchitecture

Data for the research article “VOLCO: a predictive model for 3D printed microarchitecture”</p

Multi-material 3D bioprinting of porous constructs for cartilage regeneration

© 2020 Elsevier B.V. The current gold standard for nasal reconstruction after rhinectomy or severe trauma includes transposition of autologous cartilage grafts in conjunction with coverage using an autologous skin flap. Harvesting autologous cartilage requires a major additional procedure that may create donor site morbidity. Major nasal reconstruction also requires sculpting autologous cartilages to form a cartilage framework, which is complex, highly skill-demanding and very time consuming. These limitations have prompted facial reconstructive surgeons to explore different techniques such as tissue engineered cartilage. This work explores the use of multi-material 3D bioprinting with chondrocyte-laden gelatin methacrylate (GelMA) and polycaprolactone (PCL) to fabricate constructs that can potentially be used for nasal reconstruction. In this study, we have investigated the effect of 3D manufacturing parameters including temperature, needle gauge, UV exposure time, and cell carrier formulation (GelMA) on the viability and functionality of chondrocytes in bioprinted constructs. Furthermore, we printed chondrocyte-laden GelMA and PCL into composite constructs to combine biological and mechanical properties. It was found that 20% w/v GelMA was the best concentration for the 3D bioprinting of the chondrocytes without comprising the scaffold's porous structure and cell functionality. In addition, the 3D bioprinted constructs showed neocartilage formation and similar mechanical properties to nasal alar cartilage after a 50-day culture period. Neocartilage formation was also observed in the composite constructs evidenced by the presence of glycosaminoglycans and collagen type II. This study shows the feasibility of manufacturing neocartilage using chondrocytes/GelMA/PCL 3D bioprinted porous constructs which could be applied as a method for fabricating implants for nose reconstruction