The Australian Bioprinting Workshop for Tissue Engineering and Regenerative Medicine was founded to create a community of scientists, clinicians, and engineers to work in synergy with industry, government, and regulatory agencies to tackle key challenges in the bioprinting field and facilitate the clinical translation of this promising technology¹. Annual workshops are hosted by the University of Technology Sydney (UTS) alongside company sponsorship, with support from professional 3D printing networks such as 3DHeals.

Why the Workshop?

In recent years, Australia has seen considerable growth and investment dedicated to establishing collaborative research centers to maximize research impact through industry orientated projects and clinical translation. This is supported by the several bioprinting laboratories located within a hospital, such as the Herston Biofabrication Institute at Metro North Hospital, Brisbane, and BioFab3D located within St Vincent’s Hospital, Melbourne.

These workshops seek to build upon existing collaborative partnerships to assist in publications of international scientific consensus on key developmental areas including biomaterials for bioprinting, organ-on-a-chip studies, and the bioprinting of tissue-specific models for drug development and oncology applications². Key elements in developing these events have been the principle that all member publications should reflect a consensus of those engaged in its continued discussions.

The meeting was opened by the Head of the School of Biomedical Engineering at UTS, Prof. Joanne Tipper, and Dr. Carmine Gentile, the workshop organizer, and leader of the Cardiovascular Regeneration Group both at UTS and at the Kolling Institute/the University of Sydney, followed by introducing the program for the day and chairing the opening session focusing on industry innovation, as detailed below.

Industry Innovation

The purpose of this session was to provide the opportunity to hear directly from world leaders in the field of bioprinting how commercially available bioprinting platforms are helping researchers in tackling several of the problems characteristic of bioprinted tissues. This session was opened by Dr. Manuel Figueruela García (Regemat3D) with a focus on the customization of bioprinting and bioreactor platforms that can be applied through tissue specificity for regenerative medicine applications.

Derek Mathers (Advanced Solutions Life Sciences) and Dr. Martin Engel alongside Dr. Jeremy Dobrowolski (Inventia Life Science) discussed the benefits of establishing automated workcell operations for biofabrication processes and recent advances in 3D cell culture using digital bioprinting platforms, respectively.

Dr. Haruka Yoshie (CELLINK) closed the session by detailing a range of tissue-specific applications, spanning from extrusion-based and light-activated polymers, with a focus on their limitations and possibilities associated with each fabrication modality.

Biomaterials for Bioprinting

Identifying the optimal biomaterial for bioprinting tissues and organs is one of the greatest challenges in defining the microenvironment in which cells to grow ³. Prof. Gordon Wallace and Dr. Zhilian Yue of the University of Wollongong (UOW) introduced their recent progression on biopolymers for bioinks for bioprinting, raising issues associated with the sourcing of biomaterials, processing requirements, and logistical considerations required when planning for the future clinical translation of bioprinted tissues and organs^{4, 5}.

Dr. Khoon Lim of the University of Otago opened his presentation on the use of light-activated polymers for bioprinting applications by covering aspects of photo-crosslinking approaches⁶.

Bioprinting of Organoids and Tissues

Next generation organogenesis has the potential to revolutionize many biofabrication processes. These include cosmetics testing and drug development by improving clinical trial speeds and model efficacy whilst reducing associated costs and the dependence for early-stage animal studies^{7, 8}.

Prof. Anthony Weiss of the University of Sydney summarized his group’s recent efforts in the generation and use of human recombinant elastin-based bioinks for bioprinting vascularized soft tissues⁹. Central to developing the next generation of human tissues and organs is the need to address the field’s most prominent hurdle of achieving perfusable vascularization within bioprinted constructs and in-vitro systems ^{10, 11}.

A/Prof. Jeremy Crook (UOW), Dr. Carmine Gentile (UTS), and Dr. Anita Quigley (RMIT) reported their recent progression in reproducing neuronal models12, cardiac12, and skeletal muscle models¹³, respectively.

Clinical Perspectives

Crosstalk with clinical partners is fundamental for speedy translation of findings from the bench to the bedside. Prof. Peter Choong of the University of Melbourne described his clinical perspectives for bone tissue bioprinting to open the session and how surgeons can work together with engineers and biologists to look for practical solutions to key clinical problems that typically arise from trauma and osteoarthritis. Prof. Choong outlined the regenerative potential of combing stem cells with bioprinting techniques in order to fill bone defects and by developing a handheld device for surgical applications^{14, 15}.

Dr. Liudmila Polonchuk (Hoffman La-Roche) discussed the potential use of bioprinted tissues for drug development, with an application in cardiac safety.

Commercial Pathways

The four major driving factors of bioprinting development can be attributed from increasing public and private investments in drug discovery, cosmetics testing, tissue regeneration, and medical device development¹⁶. In order to safeguard patient safety whilst aiding the successful translation of bioprinting technologies, Michelle Knight (Hydrix) discussed the regulatory requirements to ensure maximum benefit and minimum risk to the patient.

Prof. Dianne Nicol of the University of Tasmania followed by detailing the patentability of bioprinting technologies, highlighting that there are currently approximately more than 700 patents and applications worldwide with only a small percentage abandoned, suggesting an active growth phase¹⁷.

Stepping into the future

A better understanding of where the field is potentially going and where new technologies may benefit from the crosstalk between experts in different fields were the focus of this session.

Dr. Alfredo Martinez-Coll (UTS) opened the session with a presentation on market trends in bioprinting technologies, in which organ-on-a-chip models were described as playing a key role in the development of the field.

Dr. Mark Allenby of the Queensland University of Technology describing the potential of harnessing computational modeling to enhance biofabrication processes18.

Next Dr. Irina Kabakova (UTS) outlined the capabilities of 3D non-contact micromechanical characterization for bioprinted structures and materials¹⁹, followed by the final keynote presentation for the day on the magnetic levitational bioassembly of 3D tissue constructs in space by Dr. Vladimir Mironov (3D Bioprinting Solutions)²⁰. The decision to conduct bioassembly experiments of cartilage generation in space further warrants a growing vested interest in biofabrication technologies and in the evaluation of the effects of microgravity on human intervertebral discs and articular cartilages during long-term spaceflights.

Acknowledgments

The event was supported by the School of Biomedical Engineering (FEIT) at the University of Technology Sydney (UTS, Australia), and the several sponsors that supported the meeting: CELLINK, REGEMAT3D, Inventia Life Science, Cytiva, Advanced Solutions, RegenHU, Poietis, Fluicell, Lastek. A particular thanks to 3D Heals for their kind support as well.

References

1.         https://whova.com/web/biopr_202011/.

2.         Shrestha, J.; Razavi Bazaz, S.; Aboulkheyr Es, H., et al.: Lung-on-a-chip: the future of respiratory disease models and pharmacological studies.Critical Reviews in Biotechnology: 40 (2), 213-230, 2020.

3.         Groll, J.; Burdick, J.; Cho, D., et al.: A definition of bioinks and their distinction from biomaterial inks. 2018.

4.         Javadi, M.; Gu, Q.; Naficy, S., et al.: Conductive Tough Hydrogel for Bioapplications.Macromolecular Bioscience: 18 (2), 1700270, 2018.

5.         Chen, Z.; You, J.; Liu, X., et al.: Biomaterials for corneal bioengineering.Biomedical Materials: 13 (3), 032002, 2018.

6.         Lim, K. S.; Galarraga, J. H.; Cui, X., et al.: Fundamentals and Applications of Photo-Cross-Linking in Bioprinting.Chemical Reviews: 120 (19), 10662-10694, 2020.

7.         Giwa, S.; Lewis, J. K.; Alvarez, L., et al.: The promise of organ and tissue preservation to transform medicine.Nature Biotechnology: 35 (6), 530-542, 2017.

8.         Sreekala, P.; Suresh, M.; Lakshmi Priyadarsini, S.: 3D organ printing: Review on operational challenges and constraints.Materials Today: Proceedings, 2020.

9.         Lee, S.; Sani, E. S.; Spencer, A. R., et al.: Human‐Recombinant‐Elastin‐Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues.Advanced Materials, 2003915, 2020.

10.       Grover, H.; Spatarelu, C.-P.; De’De, K., et al.: Vascularization in 3D printed tissues: emerging technologies to overcome longstanding obstacles.AIMS Cell and Tissue Engineering: 2 (3), 163-184, 2018.

11.       Kim, J. J.; Hou, L.; Huang, N. F.: Vascularization of three-dimensional engineered tissues for regenerative medicine applications.Acta Biomater: 41, 17-26, 2016.

12.       Tomaskovic‐Crook, E.; Zhang, P.; Ahtiainen, A., et al.: Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation.Advanced Healthcare Materials: 8 (15), 1900425, 2019.

13.       Quigley, A. F.; Cornock, R.; Mysore, T., et al.: Wet-Spun Trojan Horse Cell Constructs for Engineering Muscle.Frontiers in Chemistry: 8, 2020.

14.       Duchi, S.; Onofrillo, C.; O’Connell, C., et al., Bioprinting Stem Cells in Hydrogel for In Situ Surgical Application: A Case for Articular Cartilage. Springer US: 2020; pp 145-157.

15.       Duchi, S.; Onofrillo, C.; O’Connell, C. D., et al.: Handheld co-axial bioprinting: application to in situ surgical cartilage repair.Scientific reports: 7 (1), 5837, 2017.

16.       Bicudo, E.; Faulkner, A.; Li, P.: Patents and the experimental space: social, legal and geographical dimensions of 3D bioprinting.International Review of Law, Computers & Technology, 1-22, 2020.

17.       Mendis, D. K.; Lemley, M. A.; Rimmer, M., 3D printing and beyond : intellectual property and regulation. Edward Elgar Publishing: 2019.

18.       Buenzli, P. R.; Lanaro, M.; Wong, C. S., et al., Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size. Cold Spring Harbor Laboratory: 2020.

19.       Wu, P.-J.; Masouleh, M. I.; Dini, D., et al.: Detection of proteoglycan loss from articular cartilage using Brillouin microscopy, with applications to osteoarthritis.Biomedical Optics Express: 10 (5), 2457, 2019.

20.       Parfenov, V. A.; Khesuani, Y. D.; Petrov, S. V., et al.: Magnetic levitational bioassembly of 3D tissue construct in space.Science Advances: 6 (29), eaba4174, 2020.

About the Author:

William Harley graduated with honors in medical biotechnology from the University of New South Wales. Currently, he is undertaking a Ph.D. at the University of Melbourne in acoustophoretic bioprinting. Stemming from his research experience in biomaterials, stem cells, and nanofabrication, he is driven by the clinical translation of personalized regenerative medicine. He is passionate about the innovation of 3D printing in healthcare and is determined to orchestrate a series of 3D HEALS events to engage in the Australian community.

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As clinical educators, we train medical and veterinary students and residents in basic and advanced clinical procedures.  The educational dilemma that exists for medical educators is how do we train students to attain competency in high-risk procedures?  Traditionally the training model has been a mentor – trainee relationship with students progressively learning and then mastering more complex clinical techniques through observation and under direct supervision in clinical patients over time.

Clinical education standards are evolving and there are requirements to document clinical competency through objective assessment rather than the demonstration of a prescribed number of cases in a case log.  This is a positive and long overdue evolution.

Training of medical or veterinary students on animals or humans for higher-risk procedures poses a potential risk to patients through longer procedure times and causes anxiety for students.  

Access to animals and cadaveric materials for use in teaching is increasingly difficult, due to ethical and cultural controversies, expense, and health and safety considerations.  

An example of a higher risk advanced procedure is performing a bronchoscopy.  Bronchoscopy involves placing a flexible endoscope into the airways to allow direct visualization and systematic investigation of the airway and sample collection.  During this procedure, adverse effects on breathing and oxygenation can occur, so the procedure must be completed in a timely manner which means limited opportunity for residents to develop the skills required to become competent.  In small animals or pediatric patients, small airway diameter and pre-existing pathology can result in rapid desaturation.

Training using physical models allows students to do practiced, repetitive-training of specific clinical skills with real-time guided direct mentor input and feedback in a safe learning environment. Lower-fidelity models are suitable for the development of basic motor and procedural skills.  The ideal clinical procedural trainer should affordable, realistic, easily stored, reusable, without the biohazard risks of animal parts, and as technically challenging as real patients. 

More advanced or higher-risk procedures require higher-fidelity models, such as virtual reality simulation, may more closely replicate the patient anatomy and clinical scenario, but are significantly more expensive.

Using 3D printed training models, technical skills can be acquired, practiced, and improved before procedures are done in people or animals.  3D models can be produced to have normal and pathological simulation scenarios to encompass the full range of procedural practice and intended learning objectives. 

We have created a 3D printed canine bronchoscopy training model at the Austin Hospitals 3DMed Lab from a thoracic CT scan of a dog.   The airway was segmented from these scans via 3D Slicer and then uploaded to Meshmixer, where further manual adjustments were made. The resultant STL was uploaded to Cura and printed with an Ultimaker S5 with white poly-lactic acid and poly-vinyl acetate support. An iterative feedback process from clinical educators and students was used to refine the model.  Features included from this feedback included: dyeing the model with red synthetic fabric dye to better replicate mucosa, including a dorsal tracheal membrane for orientation and making slight adjustments to the angle of the airways to facilitate navigation. Face and content validation of the model was conducted with 7 participants of varying experience.

The model will be introduced into clinical teaching for veterinary medicine residents in 2020.  Residents will be able to practice endoscope manipulations required to perform a standardized complete bronchoscopy examination, so they will be well prepared for doing these procedures in clinical patients.

About the Author:

Dr. Stewart Ryan, BVSc(Hons), MS, Diplomate ACVS, Founding Fellow ACVS (Surgical Oncology), Senior Lecturer and Head of Small Animal Surgery service, UVet veterinary Hospital , Faculty of Veterinary and Agricultural Sciences

Stewart is a specialist veterinary surgeon at the Melbourne Veterinary School who loves exploring ways to make surgical treatments less invasive and make complex procedures more understandable for pet owners and students through advanced technologies including minimally invasive surgery, interventional radiology and 3D models for training and education. 

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The post 3D Printed Bronchoscopy Simulator for Medical and Veterinary Training appeared first on 3DHeals.