From Academia: 3D Printing Intubation Phantom, Functional Porous Implants, Beating Cardiac Organoids

Category: Blog
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“From Academia” feature recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, bioprinting, and related emerging technologies. 

Email: Rance Tino (tino.rance@gmail.com) if you want to pen an Expert Corner blog for us or want to share relevant academic publications with us.

Patient-specific and hyper-realistic phantom for an intubation simulator with a replaceable difficult airway of a toddler using 3D printing 

Authored by Junhyeok Ock, Eunseo Gwon, Doo-hwan Kim, Sung-hoon Kim, Namkug Kim. Scientific Reports, 30 June 2020

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A patient-specific and hyper-realistic phantom for difficult tracheal intubation simulator. (A) Assembly of the inner parts, including the back of the skull, cranio-maxilla, mandible, cervical-spine, airway, and tongue in the isometric view. (B) At state, (A) bottom view. (C) Final phantom with front and rear skins. (D) Intubation with Macintosh blades in the phantom with mouth opening. Copyright.  Scientific Reports 

Abstract: 
Difficult tracheal intubation is the third most common respiratory-related adverse co-morbid episode and can lead to death or brain damage. Since difficult tracheal intubation is less frequent, trainees have fewer opportunities to perform difficult tracheal intubation; this leads to the need to practice with a hyper-realistic intubation simulator. However, conventional simulators are expensive, relatively stiffer than the human airway, and have a lack of diversity in terms of disease variations and anatomic reproducibility. Therefore, we proposed the development of a patient-specific and hyper-realistic difficult tracheal intubation simulator using three-dimensional printing technology and silicone molding and to test the feasibility of patient-specific and hyper-realistic difficult intubation simulation using 3D phantom for the trainee. This difficult tracheal intubation phantom can provide a realistic simulation experience of managing various difficult tracheal intubation cases to trainees, which could minimize unexpected tissue damage before anesthesia. To achieve a more realistic simulation, a patient-specific phantom was fabricated to mimic human tissue with realistic mouth opening and accurate difficult airway shape. This has great potential for the medical education and training field.

Functionality-packed additively manufactured porous titanium implants 

Authored by I.A.J.van Hengel, F.S.A. Gelderman, S. Athanasiadis, M. Minneboo, H. Weinans, A.C. Fluit, B.C.J. van der Eerden, L.E. Fratila-Apachitei, I. Apachitei, A.A. Zadpoor. Materials Today Bio, June 2020

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3D printing and biofunctionalizing the implant. Copyright. Materials Today Bio

Abstract: 
The holy grail of orthopedic implant design is to ward off both aseptic and septic loosening for long enough that the implant outlives the patient. Questing this holy grail is feasible only if orthopedic biomaterials possess a long list of functionalities that enable them to discharge the onerous task of permanently replacing the native bone tissue. Here, we present a rationally designed and additive manufacturing (AM) topologically ordered porous metallic biomaterial that is made from Ti-6Al-4V using selective laser melting and packs most (if not all) of the required functionalities into a single implant. In addition to presenting a fully interconnected porous structure and form-freedom that enables the realization of patient-specific implants, the biomaterials developed here were biofunctionalized using plasma electrolytic oxidation to locally release both osteogenic (i.e. strontium) and antibacterial (i.e. silver ions) agents. The same single-step biofunctionalization process also incorporated hydroxyapatite into the surface of the implants. Our measurements verified the continued release of both types of active agents for up to 28 days. Assessment of the antibacterial activity in vitro and in an ex vivo murine model demonstrated extraordinarily high levels of bactericidal effects against a highly virulent and multidrug-resistant Staphylococcus aureus strain (i.e. USA300) with total eradication of both planktonic and adherent bacteria. This strong antibacterial behavior was combined with a significantly enhanced osteogenic behavior, as evidenced by significantly higher levels of alkaline phosphatase (ALP) activity compared with non-biofunctionalized implants. Finally, we discovered synergistic antibacterial behavior between strontium and silver ions, meaning that 4–32 folds lower concentrations of silver ions were required to achieve growth inhibition and total killing of bacteria. The functionality-packed biomaterial presented here demonstrates a unique combination of functionalities that make it an advanced prototype of future orthopedic biomaterials where implants will outlive patients.

In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid

 Authored by Molly E. Kupfer, Wei-Han Lin, Vasanth Ravikumar, Kaiyan Qiu, Lu Wang, Ling Gao, Didarul B. Bhuiyan, Megan Lenz, Jeffrey Ai, Ryan R. Mahutga, DeWayne Townsend, Jianyi Zhang, Michael C. McAlpine, Elena G. Tolkacheva, Brenda M. Ogle. Circulation Research. 31 March 2020.

Abstract:
One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, the inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes—a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ. To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional chambered organoids composed of contiguous cardiac muscle. We optimized a photo-cross-linkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated the function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease. This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a testbed for cardiac medical devices and eventually lead to therapeutic tissue grafting.

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