From Academia: 3D Printed Pills, 4D Printed Structure, and how to property 3D print Chocolate

Oct 08, 2019

(About the Photo: Solid three-dimensional model of the left scapula and preoperative simulation. (a) A navigation template stuck to the removed portion of the scapula (S1). (b,d) The nylon and titanium alloy prostheses (N-S1) were printed using a mirror imaging technique. Many holes were designed at the edge of the prosthesis for soft tissue reconstruction. (c) The retained portion of the scapula (S2) and the prosthesis (N-S1) matched well via the reconstruction plate-shaped in advance. Figure credit to: Deng L, et al. )

This is our weekly selection of recently published academic abstracts focusing on topics 3DHEALS audience would be interested in. Submit your favorite publication to ([email protected])

Pharmacology

Nagoya, Japan

Drug Incorporation into Polymer Filament Using Simple Soaking Method for Tablet Preparation Using Fused Deposition Modeling. (Tagami T, et al.) Biol Pharm Bull. 2019;42(10):1753-1760. doi: 10.1248/bpb.b19-00482.

The use of three-dimensional (3D) printing technology is expanding in various fields. The application of 3D printing is expected to increase in the pharmaceutical industry after 3D-printed tablets were approved by the U.S. Food and Drug Administration (FDA). Fused deposition modeling (FDM), a type of 3D printing, has been extensively studied for the manufacturing of tablets. A drug-loaded polymer filament, the ink of FDM 3D printers, can be prepared using the hot melt extrusion method or a simple drug-soaking method. In the present study, we investigate the influence of the experimental conditions on the loading of curcumin (model drug with fluorescence) into a polyvinylalcohol polymer filament using the soaking method. We show that organic solvent type (isopropanol, methanol, acetone, and ethanol), temperature (25 and 80°C), and drug concentration (2-333 mg/mL) greatly affect drug loading. Around 5% curcumin can be incorporated into the polyvinylalcohol filament using the soaking method. The drug dissolution from 3D-printed tablets depends on the drug content in the polymer filament. The incorporation of a higher amount of curcumin, which has poor water solubility, greatly delays drug dissolution. These results provide useful information on the preparation of 3D-printed tablets using a drug-loaded polymer filament obtained with the soaking method.

Medical 3D Printing

Wuhan, P.R. China

Application of a three-dimensional printed segmental scapula prosthesis in the treatment of scapula tumors. (Deng L, et al.) J Int Med Res. 2019 Oct 3:300060519875336. doi: 10.1177/0300060519875336.

Chondrosarcoma is characterized by the presence of histologically aggressive behavior, and commonly involves the scapula. Currently, limb salvage surgery is the recommended surgical treatment. Owing to the irregularity of the tumor, the suitability of an implant after tumor resection is a challenge for surgeons. Three-dimensional (3D) printing technology has the potential to make personalized limb salvage surgery a reality. We report the case of a 53-year-old man who was diagnosed with chondrosarcoma of the scapula. Considering the low-grade malignancy and lack of invasion of the glenoid, we agreed upon segmental scapula replacement as the treatment protocol. Nevertheless, reconstruction of the irregular bony defect remaining after tumor resection can be complicated. Therefore, a personalized prosthesis and navigation template corresponding to tumor was designed with 3D printing technique, and tumor resection, prosthesis implantation, and rotator cuff reconstruction were completed. The affected shoulder achieved satisfactory function during a 32-month follow-up with no tumor recurrence. 3D printing technique can help implement the individualized design of the implant and accurate reconstruction after tumor resection, simplify complicated operations, improve operational efficiency, and allow early functional recovery.

Jacksonville, Florida

The importance of teaching clinical anatomy in surgical skills education: spare the patient, use a sim! (Clifton Wet al) Clin Anat. 2019 Oct 3. doi: 10.1002/ca.23485.

Anatomical knowledge is a key tenet in graduate medical and surgical education. Classically, these principles are taught in the operating room during live surgical experience. This puts both the learner and the patient at a disadvantage due to environment, time, and safety constraints. Educational adjuncts such as cadaveric courses and surgical skills didactics have been shown to improve resident confidence and proficiency in both anatomical knowledge and surgical techniques. However, the cost-effectiveness of these courses is a limiting factor, and in many cases prevents implementation within institutional training programs. Anatomical simulation in the form of “desktop” 3D printing provides a cost-effective adjunct while maintaining educational value. This manuscript describes the anatomical and patient-centered approach that led to the establishment of our institution’s 3D printing laboratory for anatomical and procedural education.  

Toyoma, Japan

Treatment of airway stenosis with a customized bronchial stent using a three-dimensional printer and flexible filaments. (Ojima TKitamura N) Respirol Case Rep. 2019 Sep 25;7(9):e00491. doi: 10.1002/rcr2.491. eCollection 2019 Dec.

Stent placement is recommended for patients with airway stenosis. However, ready-made stents may be difficult to fit over lesioned areas. In the current case report, we describe the creation and placement of a custom stent in an 84-year-old woman with airway stenosis. We made a bronchial mold and customized stent with a three-dimensional printer and flexible filaments. This stent was able to successfully maintain our patient’s airway patency.  

San Francisco, CA, USA

Use of three-dimensional printing and intraoperative navigation in the surgical resection of metastatic acetabular osteosarcoma. (Heunis JCet al). BMJ Case Rep. 2019 Sep 30;12(9). pii: e230238. doi: 10.1136/bcr-2019-230238.

A 21-year-old man underwent a joint-preserving posterior acetabular resection of metastatic osteosarcoma using a three-dimensional (3D) printed model and intraoperative navigation. The combined application of these advanced technologies can allow for surgical planning of osteotomies involving complex anatomy and help guide resections intraoperatively. They can maximise the achievement of negative oncological margins, preservation of native hip stability and critical neurovascular structures, and optimal postoperative function in an effort to resect all clinically evident disease. For this particular patient, with secondary bony metastases, they allowed for a safe and well-tolerated procedure that ultimately afforded him palliative benefit, improved quality of life and, conceivably, prolonged survival in the setting of a devastating prognosis. Although he, sadly, has since passed away, he survived for over 2 years after initial metastasis with preserved hip stability and the ability to graduate college, stay active and maintain a quality of life that addressed his goals of care.

Melbourne, Australia

Gyroid structures for 3D-printed heterogeneous radiotherapy phantoms.

(Tino RB, et al) 2019 Sep 27. doi: 10.1088/1361-6560/ab48ab.

The extreme customisation and rapid prototyping capabilities of the 3D printing process allows the manufacture of low-cost and patient-specific radiotherapy phantoms for quality assurance purposes. However, the associated printing techniques and materials are experimentally limited and are yet to be quantified in terms of manufacturability and reproducibility. In addition to this, there lacks research in utilising naturally inspired structures, known as Triply Periodic Minimal surfaces (TPMS), as a structural manufacturing basis for these phantoms, enabling material heterogeneity, which is a significant factor in attaining patient-specificity. We propose the use of Gyroid structures for radiotherapy phantom applications to investigate Gyroid-phantom manufacturability, the mathematical definition of Gyroids and their effects on Hounsfield Units (HU). The printed Gyroid phantoms were assessed for manufacturability using optical microscopy and micro-Computed Tomography (μCT), and material hounsfield-equivalence using standard medical CT. A mean HU range of -900 to -390 were achieved from the fabricated Gyroid phantoms with varying standard deviation. Compared to traditional printing infills such as grid and slit structures, the Gyroid phantoms were observed to produce isotropic HU and SD at varied scanning orientations, which is a favourable factor in terms of modulating the hounsfield-equivalence of printed structures. This study not only demonstrates the feasibility of manipulating the structural parameters of Gyroids in simulating tissue imaging attenuations but also opens significant research opportunities in fabricating patient-specific phantoms with added pathological features for end-to-end radiotherapy testing.

Dalian, P.R. China

Microcatheter shaping using three-dimensional printed models for intracranial aneurysm coiling. (Xu Y#1, et al.) J Neurointerv Surg. 2019 Sep 28. pii: neurintsurg-2019-015346. doi: 10.1136/neurintsurg-2019-015346.

BACKGROUND AND PURPOSE:

Microcatheterization is an important, but also difficult, technique used for the embolization of intracranial aneurysms. The purpose of this study was to investigate the application of three-dimensional (3D) printing technology in microcatheter shaping.

METHODS:

Nine cases of internal carotid artery posterior communicating artery aneurysm diagnosed by CT angiography were selected, and 3D printing technology was used to build a 3D model including the aneurysm and the parent artery. The hollow and translucent model had certain flexibility; it was immersed in water and the microcatheter was introduced into the water to the target position in the aneurysm, followed by heating the water temperature to 50°C. After soaking for 5 min, the microcatheter was taken out and the shaping was completed. After sterilization, the shaped microcatheter was used for arterial aneurysm embolization and evaluation was conducted.

RESULTS:

Nine cases of microcatheter shaping were satisfactory and shaping the needle was not necessary; no rebound was observed. The microcatheter was placed in an ideal position, and the stent-assisted method was used in three cases of wide-neck aneurysm. There were no complications related to surgery.

CONCLUSION:

A new microcatheter shaping method using 3D printing technology makes intracranial artery aneurysm embolization more stable and efficient.

Bioprinting

Rome, Italy

3D Bioprinted Human Cortical Neural Constructs Derived from Induced Pluripotent Stem Cells. (Salaris F, et al.) J Clin Med. 2019 Oct 2;8(10). pii: E1595. doi: 10.3390/jcm8101595.

Bioprinting techniques use bioinks made of biocompatible non-living materials and cells to build 3D constructs in a controlled manner and with micrometric resolution. 3D bioprinted structures representative of several human tissues have been recently produced using cells derived by differentiation of induced pluripotent stem cells (iPSCs). Human iPSCs can be differentiated in a wide range of neurons and glia, providing an ideal tool for modeling the human nervous system. Here we report a neural construct generated by 3D bioprinting of cortical neurons and glial precursors derived from human iPSCs. We show that the extrusion-based printing process does not impair cell viability in the short and long term. Bioprinted cells can be further differentiated within the construct and properly express neuronal and astrocytic markers. Functional analysis of 3D bioprinted cells highlights an early stage of maturation and the establishment of early network activity behaviors. This work lays the basis for generating more complex and faithful 3D models of the human nervous systems by bioprinting neural cells derived from iPSCs.

Melbourne Australia

Layer-By-Layer: The Case for 3D Bioprinting Neurons to Create Patient-Specific Epilepsy Models. (Antill-O’Brien N,et al.)  Materials (Basel). 2019 Oct 1;12(19). pii: E3218. doi: 10.3390/ma12193218.

The ability to create three-dimensional (3D) models of brain tissue from patient-derived cells, would open new possibilities in studying the neuropathology of disorders such as epilepsy and schizophrenia. While organoid culture has provided impressive examples of patient-specific models, the generation of organized 3D structures remains a challenge. 3D bioprinting is a rapidly developing technology where living cells, encapsulated in suitable bioink matrices, are printed to form 3D structures. 3D bioprinting may provide the capability to organise neuronal populations in 3D, through layer-by-layer deposition, and thereby recapitulate the complexity of neural tissue. However, printing neuron cells raises particular challenges since the biomaterial environment must be of appropriate softness to allow for the neurite extension, properties which are anathema to building self-supporting 3D structures. Here, we review the topic of 3D bioprinting of neurons, including critical discussions of hardware and bio-ink formulation requirements.

Dalian, P.R.China.

3D Bio-Printing of CS/Gel/HA/Gr Hybrid Osteochondral Scaffolds.

(Hu X1, et al.) Polymers (Basel). 2019 Sep 30;11(10). pii: E1601. doi: 10.3390/polym11101601.

Cartilage is an important tissue contributing to the structure and function of support and protection in the human body. There are many challenges for tissue cartilage repair. However, 3D bio-printing of osteochondral scaffolds provides a promising solution. This study involved preparing bio-inks with different proportions of chitosan (Cs), Gelatin (Gel), and Hyaluronic acid (HA). The rheological properties of each bio-ink was used to identify the optimal bio-ink for printing. To improve the mechanical properties of the bio-scaffold, Graphene (GR) with a mass ratio of 0.024, 0.06, and 0.1% was doped in the bio-ink. Bio-scaffolds were prepared using 3D printing technology. The mechanical strength, water absorption rate, porosity, and degradation rate of the bio-scaffolds were compared to select the most suitable scaffold to support the proliferation and differentiation of cells. P3 Bone mesenchymal stem cells (BMSCs) were inoculated onto the bio-scaffolds to study the biocompatibility of the scaffolds. The results of SEM showed that the Cs/Gel/HA scaffolds with a GR content of 0, 0.024, 0.06, and 0.1% had a good three-dimensional porous structure and interpenetrating pores, and a porosity of more than 80%. GR was evenly distributed on the scaffold as observed by energy spectrum analyzer and polarizing microscope. With increasing GR content, the mechanical strength of the scaffold was enhanced, and pore walls became thicker and smoother. BMSCs were inoculated on the different scaffolds. The cells distributed and extended well on Cs/Gel/HA/GR scaffolds. Compared to traditional methods in tissue-engineering, this technique displays important advantages in simulating natural cartilage with the ability to finely control the mechanical and chemical properties of the scaffold to support cell distribution and proliferation for tissue repair.

San Diego, CA, USA

Rapid 3D bioprinting of in vitro cardiac tissue models using human embryonic stem cell-derived cardiomyocytes. (Liu J, et al.) Bioprinting. 2019 Mar;13. pii: e00040. doi: 10.1016/j.bprint.2019.e00040. Epub 2019 Jan 10.

There is a great need for physiologically relevant 3D human cardiac scaffolds for both short-term, the development of drug testing platforms to screen new drugs across different genetic backgrounds, and longer term, the replacement of damaged or non-functional cardiac tissue after injury or infarction. In this study, we have designed and printed a variety of scaffolds for in vitro diagnostics using light based Micro-Continuous Optical Printing (μCOP). Human embryonic stem cell-derived cardiomyocyte (hESC-CMs) were directly printed into gelatin hydrogel on glass to determine their viability and ability to align. The incorporation of Green Fluorescent Protein/Calmodulin/M13 Peptide (GCaMP3)-hESC-CMs allowed the ability to continuously monitor calcium transients over time. Normalized fluorescence of GCaMP3-hESCCMs increased by 18 ± 6% and 40 ± 5% when treated with 500 nM and 1 μM of isoproterenol, respectively. Finally, GCaMP3-hESC-CMs were printed across a customizable 3D printed cantilever-based force system. Along with force tracking by visualizing the displacement of the cantilever, calcium transients could be observed in a non-destructive manner, allowing the samples to be examined over several days. Our μCOP-printed cardiac models presented here can be used as a powerful tool for drug screening and to analyze cardiac tissue maturation.

3D Printing Food:

Singapore University of Technology and Design

Chocolate-based Ink Three-dimensional Printing (Ci3DP).

Karyappa RHashimoto  MSci Rep. 2019 Oct 2;9(1):14178. doi: 10.1038/s41598-019-50583-5.

Recent advances in three-dimensional (3D) printing technology has enabled to shape food in unique and complex 3D shapes. To showcase the capability of 3D food printing, chocolates have been commonly used as printing inks, and 3D printing based on hot-melt extrusion have been demonstrated to model 3D chocolate products. Although hot-melt extrusion of chocolates is simple, the printing requires precise control over the operating temperature in a narrow range. In this work, for the first time, we directly printed chocolate-based inks in its liquid phase using direct ink writing (DIW) 3D printer to model complex 3D shapes without temperature control. We termed this method as chocolate-based ink 3D printing (Ci3DP). The printing inks were prepared by mixing readily available chocolate syrup and paste with cocoa powders at 5 to 25 w/w% to achieve desired rheological properties. High concentrations of cocoa powders in the chocolate-based inks exhibited shear-thinning properties with viscosities ranging from 102 to 104 Pa.s; the inks also possessed finite yield stresses at rest. Rheology of the inks was analyzed by quantifying the degree of shear-thinning by fitting the experimental data of shear stress as a function of shear rate to Herschel-Bulkley model. We demonstrated fabrication of 3D models consisting of chocolate syrups and pastes mixed with the concentration of cocoa powders at 10 to 25 w/w%. The same method was extended to fabricate chocolate-based models consisting of multiple type of chocolate-based inks (e.g. semi-solid enclosure and liquid filling). The simplicity and flexibility of Ci3DP offer great potentials in fabricating complex chocolate-based products without temperature control.

Material Science:

Boston, MA, USA

Shape-shifting structured lattices via multimaterial 4D printing.

(Boley JW1,2,3, et al) Proc Natl Acad Sci U S A. 2019 Oct 2. pii: 201908806. doi: 10.1073/pnas.1908806116.

Shape-morphing structured materials have the ability to transform a range of applications. However, their design and fabrication remain challenging due to the difficulty of controlling the underlying metric tensor in space and time. Here, we exploit a combination of multiple materials, geometry, and 4-dimensional (4D) printing to create structured heterogeneous lattices that overcome this problem. Our printable inks are composed of elastomeric matrices with tunable cross-link density and anisotropic filler that enable precise control of their elastic modulus (E) and coefficient of thermal expansion. The inks are printed in the form of lattices with curved bilayer ribs whose geometry is individually programmed to achieve local control over the metric tensor. For independent control of extrinsic curvature, we created multiplexed bilayer ribs composed of 4 materials, which enables us to encode a wide range of 3-dimensional (3D) shape changes in response to temperature. As exemplars, we designed and printed planar lattices that morph into frequency-shifting antennae and a human face, demonstrating functionality and geometric complexity, respectively. Our inverse geometric design and multi-material 4D printing method can be readily extended to other stimuli-responsive materials and different 2-dimensional (2D) and 3D cell designs to create scalable, reversible, shape-shifting structures with unprecedented complexity.

FuZhou, P.R. China

Dynamic imine bonds based shape memory polymers with permanent shape reconfigurability for 4D printing. (Miao JT, et al) ACS Appl Mater Interfaces. 2019 Oct 2. doi: 10.1021/acsami.9b14145.

Shape memory polymer (SMP)-based 4D printing combines the advantages of SMP and 3D printing to form active materials with delicate structure. Nowadays, studies of SMP-based 4D printing materials mainly focus on crosslinked (meth)acrylate, of which the permanent shape cannot be changed for their covalent linkage, limiting the usage of 4D printing materials. In this paper, a novel methacrylate monomer with aldehyde group (2-(methacryloyloxy)ethyl 4-formylbenzoate, MEFB) and hyperbranched crosslinker (HPASi) are synthesized to build (meth)acrylate systems (IEMSis) with dynamic imine bonds for 4D printing. The flexible chain structure of HPASi significantly enhances the toughness of IEMSis, which are 33-97-fold higher than that of the one without HPASi (IEM). The addition of HPASi also endows IEMSis good shape memory properties, and the shape fixity ratio and shape recovery ratio of them are 97.5-97.6 % and 91.4-93.7 %, respectively. At the same time, IEMSis can undergo stress relaxation process by dynamic exchanges of imine bonds under relatively mild conditions without catalyst, thus to acquire an ability of permanent shape reconfiguration. The shape retention ratio of IEMSi3 is 84.3 %. In addition, the 4D printed structures displayed here indicate that these 4D printing systems have a myriad of potential applications including aerospace structures, soft robotic grippers and smart electron switches, while the reconfigurability shown by IEMSi3 will expand the scope of application fields of 4D printing materials.

Shenzhen, P.R. China

A shear-thinning adhesive hydrogel reinforced by photo-initiated crosslinking as a fit-to-shape tissue sealant. (Bian S , et al.) J Mater Chem B. 2019 Oct 2. doi: 10.1039/c9tb01521c.  

Surgical sealants suitable for wounds with non-flat complex geometries are still a challenge to fulfill clinical requirements. Herein, a novel fit-to-shape sealant enhanced by photo-initiated crosslinking was developed utilizing maleic anhydride modified chitosan (MCS), benzaldehyde-terminated PEG (PEGDF) and polyethylene glycol diacrylate (PEGDA). Initially, the shear-thinning hydrogel prepared through the Schiff-base linkage between MCS and PEGDF could be injected into target sites, remolded to conform to a wound with non-flat complex geometry, and remain on the wound, avoiding adverse liquid leakage. Under illumination with ultra-violet (UV) light, the hydrogel was solidified in situ rapidly to adopt the wound contour and enhanced in adhesive strength to seal defects of the tissue. In addition, the hydrogel exhibits stability in extreme pH environments (pH = 1) and has potential to treat wounds inside the stomach with the existence of gastric acid. Moreover, the hydrogel can be applied as adhesive wound dressings through in situ 3D printing. Taken together, the fit-to-shape sealant enhanced by photo-initiated crosslinking can be considered as promising tissue adhesives for wound closure and other biomedical applications.

VR/AR/3D Visualization

Hungary

[Treatment of Theory of Mind deficits in schizophrenia by using Virtual Reality, the VR-ToMIS training (Virtual Reality based Theory of Mind Intervention in Schizophrenia)].

[Article in Hungarian] (Vass E, et al.)

Rapid development in information technology has been observed recently and has led to valuable developments also in healthcare. 3D-bio-printing or the virtual simulations that help the acquisition of anatomical and pathological knowledge and testing the acquired knowledge are just some of the examples. This progress can be recognized also in psychiatry. One of the most spectacular ways of using these technologies in psychiatry might be the therapeutic techniques associated with Virtual Reality (VR) simulations, which are currently available for anxiety disorders, eating disorders and addictions. A research team of the Psychiatric and Psychotherapeutic Department of the Semmelweis University has developed a Virtual Reality-based intervention that fits in with this perspective. The intervention mainly aims at Theory of Mind deficit and pragmatic language impairment in schizophrenia. In this article the current status of our research team’s work will be presented. The article reviews the literature that provides the basis for the development, leads the reader through the main stages of the development process, and finally the program itself will be introduced. Process and mechanism of change associated with the intervention and the potential risks of the use of VR will also be discussed.

Comments