3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution

Abstract

In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meet patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid: glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.

Spatiotemporal control of growth factors in three-dimensional printed scaffolds

“…In extrusion based techniques, the resolution is limited to around 200 μm and is generally improved by using smaller diameter needles/nozzles. (25,37,38) Smaller diameter needles, in turn, require lower bioink viscosity for effective extrusion, and the viscosity of an ink formulation varies based on parameters related to the print material itself – such as molecular weight and chemical composition – to printing conditions such as temperature and pneumatic pressure. (37) Improving the resolution of printing and by extension, of growth factor patterning in extrusion-based systems, thus requires experimental determination of the optimal print conditions for one’s bioink of choice.…”

“…(25,37,38) Smaller diameter needles, in turn, require lower bioink viscosity for effective extrusion, and the viscosity of an ink formulation varies based on parameters related to the print material itself – such as molecular weight and chemical composition – to printing conditions such as temperature and pneumatic pressure. (37) Improving the resolution of printing and by extension, of growth factor patterning in extrusion-based systems, thus requires experimental determination of the optimal print conditions for one’s bioink of choice. For inkjet systems, the resolution of printing is instead determined by droplet size instead, which is presently limited to about 1 picoliter or approximately 12 μm in diameter due to physical factors of droplet generation.…”

Biofabrication of multiscale bone extracellular matrix scaffolds for bone tissue engineering

“…An obvious advantage of 3D printing for bone tissue engineering is the capacity to control scaffold pore size and interconnectivity, which in turn regulates angiogenesis and osteogenesis within the construct (Karageorgiou and Kaplan, 2005). The most commonly used synthetic polymers for 3D printing of bone tissue engineering scaffolds are polycaprolactone (PCL) (Daly et al, 2016;De Santis et al, 2011;Hung et al, 2016;Kim and Son, 2009;Nyberg et al, 2017;Park et al, 2011;Park et al, 2012;Seyednejad et al, 2012;Temple et al, 2014;Yilgor et al, 2008) and poly(lactic-co-glycolic acid) (PLGA) (Ge et al, 2009a;Ge et al, 2009b;Guo et al, 2017;Park et al, 2012;Shim et al, 2014). Although such synthetic polymers can be used to generate mechanically stable scaffolds, on their own, they are not osteoconductive.…”

Living cell-only bioink and photocurable supporting medium for printing and generation of engineered tissues with complex geometries

“…Digital imaging data, obtained from computed tomography scans and magnetic resonance imaging, provide instruction for the desired geometry of printed constructs 7,8 . Biodegradable thermoplastics, such as polycaprolactone, polylactic acid, and poly(lactic-co-glycolic acid), are advantageous for printing as stable constructs with delicate structural control can be formed due to the mechanical integrity of original materials [9][10][11] . However, a major drawback is that cells cannot be printed simultaneously due to the use of organic solvents or high temperature to extrude the polymer inks 12 .…”