From Academia: 3D Printing and Robotics, Stem cell coated Implants, Decentralized Mitigation of Pandemics

Innovation in silos is dangerous. What’s equally unrealistic is to think that 3D printing will be the only force that will save the world. It will not. Often times, several technologies can work together to create something much more powerful. Several articles in this week’s selection demonstrated the merge of robotics and 3D printing technologies, with various application. One particular fun read was from an Italian group that created a self-growing obstacle avoiding robot that also simultaneous acts as a 3D-printer, enabling a tree-root like growth through an artificial pathway. What healthcare application can you think with that technology? Relating to my recent visit to the Cleveland Clinic, autonomous robotic surgery may not be as far as you can imagine. Another equally intriguing paper was by an Isreali group focusing on decentralized mitigation of world pandemics. This paper has more math than perhaps we want, but it is a serious discussion on how 3D printing can be leveraged in solving public health issues. I have touched upon decentralized healthcare in the past from a different angle. 

From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies.

Email: Rance Tino (tino.rance@gmail.com) if you want to share relevant academic publications with us.

Improvement of osseointegration by recruiting stem cells to titanium implants fabricated with 3D printing

Authored by Mary Bollman, Raphael Malbrue, Chunhong Li, Hong Yao, Shengmin Guo, Shaomian Yao. ANNALS of the New York Academy of Sciences. October 11 2019.

Slow and incomplete osseointegration and loss of osseointegration are major problems in dental and bone implants. We designed implants with interconnected 3D-tubulous structures and hypothesized that such interconnecting 3D (I3D) structures would serve as a repository for chemo-attractants to recruit stem cells to promote osseointegration. A concept Laser Mlab-cusing-R laser-powder-bed-fusion (LPBF) 3D printing system was used to produce titanium implants with designed features. The implants were loaded (coated) with stromal cell-derived factor-1 alpha (SDF-1α),  and subjected to stem cell recruitment. Implants were then surgically transplanted into the rabbit skull bone. After 12 weeks, osseointegration was analyzed by reverse-torque test and the implants were examined for calcium deposition by Alizarin Red staining. The I3D implants attracted significantly more stem cells than solid implants when coated (loaded) with SDF-1α. Greater torque force was needed to extract the I3D implants with 200 and 300 µm I3D structures than to extract solid implants from the skull. Generally, more calcium deposition was observed on the I3D implants than on the solid counterparts. LPBF 3D printing can be used to fabricate implants with complex structures. I3D-tubulous structures of implants can retain chemoattractant for recruitment of stem cells to enhance osseointegration.

Immobilization of BMP-2-derived peptides on 3D-printed porous scaffolds for enhanced osteogenesis.

Authored by Xiashiyao Zhang, Qi Lou, Lili Wang, Shan Min, Meng Zaho, and Changyun Quan. Biomedical Materials. November 15 2019.

Three-dimensional (3D) printing technologies open new perspectives for customizing the external shape together with the internal architecture of bone scaffolds. In this study, an oligopeptide (SSVPT, Ser-Ser-Val-Pro-Thr) derived from bone morphogenetic protein 2 was conjugated with a dopamine coating of a 3D printed poly(lactic acid) (PLA) scaffold to enhance osteogenesis. Cell experiments in vitro showed that the scaffold was highly osteoconductive to the adhesion and proliferation of rat marrow mesenchymal stem cells (MSCs). In addition, RT-PCR analysis showed that the scaffold could promote the expression of osteogenesis-related genes, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN). Images of micro-CT 3D reconstruction from the rat cranial bone defects model showed that bone regeneration patterns occurred from one side edge towards the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore further the application potential of this bioactive scaffold.

CT and MRI compatibility of flexible 3D printed materials for soft actuators and robots used in image-guided interventions.

Authored by Wiebke Neumann, Tim P. Pusch, Marius Siegfarth, Lothar R. Schad, Jan L. Stallkamp. Medical Physics. October 6 2019.

PURPOSE:

3D printing allows for the fabrication of medical devices with complex geometries, such as soft actuators and robots that can be used in image-guided interventions. This study investigates flexible and rigid 3D printing materials in terms of their impact on multimodal medical imaging.

METHODS:

The generation of artifacts in clinical CT and MR imaging was evaluated for six flexible and three rigid materials, each with a cubical and a cylindrical geometry, and for one exemplary flexible fluidic actuator. Additionally, CT Hounsfield units (HU) were quantified for various parameter sets iterating peak voltage, X-ray tube current, slice thickness and convolution kernel.

RESULTS:

We found the image artifacts caused by the materials to be negligible in both CT and MR images. The HU values mainly depended on the elemental composition of the materials and applied peak voltage ranging between 80 kVp to 140 kVp. Flexible, non-silicone-based materials ranged between 51 HU and 114 HU. The voltage dependency was less than 29 HU. Flexible, silicone-based materials ranged between 60 HU and 365 HU. The voltage-dependent influence was as large as 172 HU. Rigid materials ranged between -69 HU and 132 HU. The voltage-dependent influence was less than 33 HU.

CONCLUSION:

All tested materials may be employed for devices placed in the field of view during CT and MR imaging as no significant artifacts were measured. Moreover, the material selection in CT could be based on the desired visibility of the material depending on the application. Given the wide availability of the tested materials, we expect our results to have a positive impact on the development of devices and robots for image-guided interventions.

Passive Morphological Adaptation for Obstacle Avoidance in a Self-Growing Robot Produced by Additive Manufacturing

Authored by Ali Sadeghi, Emanuela Del Dottore, Alessio Mondini, and Barbara Mazzolai. Soft Robotics. February 6 2020.

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Figure 1. (A) Schematic view of the growing robot with feeding mechanism to automatically prevent the twisting of PLA filament with wires for power and communication. (B) Tip section view with two bearings for decoupling the tip from the rotation of the deposition mechanism. (C) Detailed view of the growing mechanism. (D) Close view of the hollow slip ring to avoid cable twisting. PLA, polylactic acid. Color images are available online. Copyright. Soft Robotics

This article presents strategies for the passive path and morphological adaptation of a plant-inspired growing robot that can build its own body by an additive manufacturing process. By exploiting the soft state of the thermoplastic material used by the robot to build its structure, we analyzed the ability of the robot to change its direction of growth without the need for specific cognition and control processes. Obstacle avoidance is computed by the mechanics from the body-environment interaction. The robot can passively adapt its body to flat obstacles with an inclination of up to 50° with resulting reaction forces of up to ∼10 N. The robot also successfully performs penetration and body adaptation (with 30° obstacle inclination) in artificial soil and in a rough unstructured environment. This approach is founded on observing plant roots and how they move and passively adapt to obstacles in soil before they actively respond followed by cell division-based growth.

Digitizable therapeutics for decentralized mitigation of global pandemics

Authored by Adar Hacohen, Reuven Cohen, Sol Efroni, Baruch barzel and Ido Bachelet. Nature Scientific Reports. October 4 2019.

When confronted with a globally spreading epidemic, we seek efficient strategies for drug dissemination, creating a competition between supply and demand at a global scale. Propagating along similar networks, e.g., air-transportation, the spreading dynamics of the supply vs. the demand are, however, fundamentally different, with the pathogens driven by contagion dynamics, and the drugs by commodity flow. We show that these different dynamics lead to intrinsically distinct spreading patterns: while viruses spread homogeneously across all destinations, creating a concurrent global demand, commodity flow unavoidably leads to a highly uneven spread, in which selected nodes are rapidly supplied, while the majority remains deprived. Consequently, even under ideal conditions of extreme production and shipping capacities, due to the inherent heterogeneity of network-based commodity flow, efficient mitigation becomes practically unattainable, as homogeneous demand is met by highly heterogeneous supply. Therefore, we propose here a decentralized mitigation strategy, based on local production and dissemination of therapeutics, that, in effect, bypasses the existing distribution networks. Such decentralization is enabled thanks to the recent development of digitizable therapeutics, based on, e.g., short DNA sequences or printable chemical compounds, that can be distributed as digital sequence files and synthesized on location via DNA/3D printing technology. We test our decentralized mitigation under extremely challenging conditions, such as suppressed local production rates or low therapeutic efficacy, and find that thanks to its homogeneous nature, it consistently outperforms the centralized alternative, saving many more lives with significantly less resources.

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