Abstract
There is an unmet need for artificial tissue to address current limitations with donor organs and problems with donor site morbidity. Despite the success with sophisticated tissue engineering endeavours, which employ cells as building blocks, they are limited to dedicated labs suitable for cell culture, with associated high costs and long tissue maturation times before available for clinical use. Direct 3D printing presents rapid, bespoke, acellular solutions for skull and bone repair or replacement, and can potentially address the need for elastic tissue, which is a major constituent of smooth muscle, cartilage, ligaments and connective tissue that support organs. Thermoplastic polyurethanes are one of the most versatile elastomeric polymers. Their segmented block copolymeric nature, comprising of hard and soft segments allows for an almost limitless potential to control physical properties and mechanical behaviour. Here we show direct 3D printing of biocompatible thermoplastic polyurethanes with Fused Deposition Modelling, with a view to presenting cell independent in-situ tissue substitutes. This method can expeditiously and economically produce heterogenous, biomimetic elastic tissue substitutes with controlled porosity to potentially facilitate vascularisation. The flexibility of this application is shown here with tubular constructs as exemplars. We demonstrate how these 3D printed constructs can be post-processed to incorporate bioactive molecules. This efficacious strategy, when combined with the privileges of digital healthcare, can be used to produce bespoke elastic tissue substitutes in-situ, independent of extensive cell culture and may be developed as a point-of-care therapy approach.
Highlights
The long-standing desire to repair or replace, damaged or diseased organs,[1,2,3,4,5,6] was reflected in ancient mythology, biblical stories and in fiction, before it evolved into a scientific and clinical plausibility (Supplementary Figure 1)
We have 3D printed tubular structures (Supplementary Figure 4) and have evaluated the definition and the structural integrity of prints. (Fig. 1a) The surface architecture of 3D tubular scaffolds, printed with TPU90, demonstrated design flexibility and definition, with the surface area of a pore of a given pattern found to be inversely proportional to the infill density. (Fig. 1a and b) The hexagonal style infill produced a more compliant structure compared to a linear infill of the same density without compromise to pore quality (Fig. 1b)
We demonstrated simple material anisotropy dependant on infill pattern with biaxial test Thermoplastic polyurethanes (TPU) printed structures (n = 5) (Supplementary Figure 6, Fig. 1c i, ii, iii)
Summary
The long-standing desire to repair or replace, damaged or diseased organs,[1,2,3,4,5,6] was reflected in ancient mythology, biblical stories and in fiction, before it evolved into a scientific and clinical plausibility (Supplementary Figure 1). 3D printing and associated multidisciplinary technologies present incredible opportunities for developing bespoke prostheses, with flexible design capabilities and greater geometric accuracy for tissue engineering.[2] Fused deposition modelling (FDM) is one of the most widely used 3D printing techniques. This methodology for building 3D structure can facilitate material anisotropy, which is an attractive feature when aiming for hetergenous tissue biomimicry. A range of thermoplastic polymers including Thermoplastic polyurethanes (TPU) have been demonstrated as being 3D printable using FDM,[10, 11] as well as the more commonly used polycaprolactone (PCL) and polylactic acid (PLA.12, 13) PLA and PCL are inherently relatively stiff materials, and as a consequence their application is limited—materials that offer greater flexibility, and tailorability to the application at hand such as TPU are desired
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