Abstract
The rising prevalence of high throughput screening and the general inability of (1) two dimensional (2D) cell culture and (2)in vitrorelease studies to predictin vivoneurobiological and pharmacokinetic responses in humans has led to greater interest in more realistic three dimensional (3D) benchtop platforms. Advantages of 3D human cell culture over its 2D analogue, or even animal models, include taking the effects of microgeometry and long-range topological features into consideration. In the era of personalized medicine, it has become increasingly valuable to screen candidate molecules and synergistic therapeutics at a patient-specific level, in particular for diseases that manifest in highly variable ways. The lack of established standards and the relatively arbitrary choice of probing conditions has limitedin vitrodrug release to a largely qualitative assessment as opposed to a predictive, quantitative measure of pharmacokinetics and pharmacodynamics in tissue. Here we report the methods used in the rapid, low-cost development of a 3D model of a mucopolysaccharidosis type I patient’s corpus callosum, which may be used for cell culture and drug release. The CAD model is developed fromin vivobrain MRI tracing of the corpus callosum using open-source software, printed with poly (lactic-acid) on a Makerbot Replicator 5X, UV-sterilized, and coated with poly (lysine) for cellular adhesion. Adaptations of material and 3D printer for expanded applications are also discussed.
Highlights
Mucopolysaccharidosis (MPS) is a spectrum of inheritable conditions involving the accumulation of glycosaminoglycans (GAGs) following disruption of key lysosomal enzymes, which in turn leads to complications on a cellular, tissue, and organ level[1]
In MPS type I (MPS I), which is characterized by a deficiency of the enzyme α-L-iduronidase, brain MRI scans reveal thinning of white matter and lesions within the periventricular area and especially the corpus callosum (CC)[2]
MPS I leads to patientspecific, irregular white matter density and geometry in the CC
Summary
Mucopolysaccharidosis (MPS) is a spectrum of inheritable conditions involving the accumulation of glycosaminoglycans (GAGs) following disruption of key lysosomal enzymes, which in turn leads to complications on a cellular, tissue, and organ level[1]. The top of the surface was dipped (Figure 1d), as this was the area of interest where the drug delivery materials would be loaded, but for other applications discussed, the entire structure can be dipped into ~50 mL of the poly-L-lysine solution for complete cell adhesion on the top and bottom. For cell culture, this object would be used in a sterile flask, or alternatively, a larger sterilized container. Care must be taken to ensure that the release kinetic probing molecule’s absorbance or emission spectra are not greatly interfered with by cell culture media
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