HMB301 - Axolotl Biosciences Literature Review Poster by Congrong He https://padlet.com/rubyhe2/vrwckriyrneletxr Made by Shesha Taylor and Ruby He en-us 2022-11-29 03:43:18 UTC 2022-11-29 17:15:32 UTC hello@padlet.com Acknowledgments rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286405 This poster was made by Shesha Taylor and Ruby He collaboratively. We would like to thank Alex and Tara from Axolotl Biosciences and Professor Naomi Levy-Strumpf for this internship opportunity.

Introduction to the company & Microcarriers - Ruby
Personalized medicine & potential uses - Shesha
Search methodology & References - Shesha & Ruby]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286405 Introduction of Axolotl Biosciences rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286408 Axolotl Biosciences is a startup founded in 2020 by Dr. Stephanie Willerth, Dr. Laura De la Vega, and Laila Abelseth in Victoria, BC. Their mission is to provide bioinks, 3D tissue models, and consulting services for 3D bioprinting in the field of tissue engineering and regenerative medicine. The major products include TissuePrint, an innovative bioink allowing high-quality tissue printing in various bioprinters. This new bioink is capable of maintaining cell viability for over a month! We were asked to conduct a literature review to investigate Microcarrier technology and its implications in personalized medicine which could lead to potential investment and products using this technology by Axolotl Biosciences.


]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286408 The core of Axolotl: Bioprinting in the Field of Tissue Engineering and Regenerative Medicine rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286409 Bioprinting is a technology using cells and biomaterials to generate 3D constructs that are functional 3D tissues. The cells or biomaterials used to replace traditional metals or plastics as 3D bioprinters use bioink which is composed of many organic and inorganic substances like collagen, ECM based material, polyethylene glycol, etc. The bioprinting technique helps generate reliable and accurate human tissue models with complex structures to apply in drug screening and disease modeling. ]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286409 Overview of Literature Review Project rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286410 In our literature review, we highlight the current advance in translational research in bioprinting based on cell expansion techniques using microcarriers, with a specific scoping of its potential in the field of personalized medicine. As a promising solution of cell expansion for the scaling-up of 3D bioprinting, microcarrier technique has great potential in stem cell research, bone regeneration, and tissue transplantation studies. The pipeline for the literature search of each category is shown in the flowchart.]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286410 Microcarriers for Cell Culture rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286411 Microcarrier-based cell culture is an innovative approach that uses the microcarrier culture technique, a cell culture strategy using microspheres as the support for cell growth. A microcarrier is a supportive structure with interconnected pores in a spherical particle, which allows cells to attach and grow on its surface (Hospodiuk et al. 2017). ]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286411 Recent Advance in Bioprinting Using Microcarriers rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286414 Microcarriers have been applied in bioprinting to solve the problem of traditional cell culture techniques in guiding specific cell differentiation and generating sufficient cells.
In 2014, Levato et al. applied microcarriers in bioprinting as a mechanical reinforcement to the soft hydrogel matrix, which helps to control the morphology of seeded cells, and supports the cell differentiation for tissue-engineered constructs. ]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286414 Case study for Microcarriers in Personalized Medicine rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286416 Dashtimoghadam et al. used microcarriers seeded with MSCs, essential proteins and growth factors to pursue bone tissue healing. They were injected into a hydrogel with endothelial cells. When these microcarriers were implanted in-vivo mouse models, there was:

- Microcarriers implanted in-vivo mouse models showed greater attachment and proliferation of MSCs which could play a pivotal role in sustaining more cells for future stem cell therapy. 
- Analysis of the MSCs in the microcarriers showed they were capable of vascular growth and bone cell differentiation, suggesting that growing organoids could be a possibility in the future, as the cells start to differentiate and form external connective materials like vascular tissue 
- Possibility of long term bone ECM chemical delivery 
- Reliable 3D microenvironment for personalized cell therapies. 

The methodology is versatile and can be used in other cells too for personalized regenerative medicine.]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286416 Importance of Personalized Medicine using Microcarriers rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286417 A major application of this would be organ and tissue transplantations, since there is a shortage of organs, leading to the death of 17 people every day, according to the U.S. Department of Health & Human Services. Additionally, after the organ transplant, patients must take immunosuppressants which can lead the patient to die from illnesses like the common cold, according to Fred Hutch Cancer centre. Due to these complications, being able to print the tissues or cells that a patient need would create a solution which would not have the complications of a donated organ (Leberfinger et al. 2019).

Advantages:
- Lessens likelihood of rejection in patients with transplants due to a failure in integration between the host and graft tissue through iPSC derived cells
- Allows proliferation in a greater capacity compared to standard cell culture techniques 
- Easier delivery of growth factors and other media
- Higher efficiency in cell growth

]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286417 Potential Areas of Personalized Medicine to Harness Microcarriers rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286418 As a promising solution for cell expansion in scaling-up 3D bioprinting, microcarriers have great potential in stem cell research, bone regeneration, and tissue transplantation studies. ]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286418 Personalized Medicine rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286419 Personalized medicine is a rapidly emerging field as advancements in healthcare allow solutions to be patient-centric and heavily make use of their genetic information. An example is the used of induced pluripotent stem cells (iPSCs) which can be derived from patient-specific somatic cells and can be reprogrammed into the needed cell type (Takahashi et al. 2007). These cells can be grown into tissues and organoids for drug testing specific to the patient. There are a multitude of other creative approaches that make use of this technology. A new pathway for personalized medicine would be to harness the microcarrier technology to rapidly expand currently available solutions.]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286419 References rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286420
  • Common cold can be surprisingly dangerous for transplant patients. 2017 Mar 7. Fred Hutch. [accessed 2022 Nov 18]. 
  • https://www.fredhutch.org/en/news/center-news/2017/03/common-cold-can-be-surprisingly-dangerous-for-transplant-patients.html.
  • Dashtimoghadam E, Fahimipour F, Tongas N, Tayebi L. 2020. Microfluidic fabrication of microcarriers with sequential delivery of VEGF and BMP-2 for bone regeneration. Scientific Reports. 10(1). doi:10.1038/s41598-020-68221-w. 
  • Go G, Yoo A, Kim S, Seon JK, Kim C-S, Park J-O, Choi E. Magnetization-Switchable Implant System to Target Delivery of Stem Cell-Loaded Bioactive Polymeric Microcarriers. Advanced Healthcare Materials. 2021 [accessed 2022 Nov 28];10(19):2100068. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202100068. doi:10.1002/adhm.202100068
  • Hospodiuk M, Dey M, Sosnoski D, Ozbolat IT. The bioink: A comprehensive review on bioprintable materials. Biotechnology Advances. 2017 [accessed 2022 Nov 9];35(2):217–239.https://www.sciencedirect.com/science/article/pii/S0734975016301719. doi:10.1016/j.biotechadv.2016.12.006
  • HRSA. 2022 Mar. Organ Donation Statistics | organdonor.gov. wwworgandonorgov. https://www.organdonor.gov/learn/organ-donation-statistics.
  • Leberfinger AN, Dinda S, Wu Y, Koduru SV, Ozbolat V, Ravnic DJ, Ozbolat IT. 2019. Bioprinting functional tissues. Acta Biomaterialia. 95:32–49. doi:10.1016/j.actbio.2019.01.009. 
  • Levato R, Visser J, Planell JA, Engel E, Malda J, Mateos-Timoneda MA. Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers. Biofabrication. 2014 [accessed 2022 Oct 30];6(3):035020.https://dx.doi.org/10.1088/1758-5082/6/3/035020. doi:10.1088/1758-5082/6/3/035020
  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. 2008. Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors. Obstetrical & Gynecological Survey. 63(3):153. doi:10.1097/01.ogx.0000305204.97355.0d.
  • Tavassoli H, Alhosseini SN, Tay A, Chan PPY, Weng Oh SK, Warkiani ME. Large-scale production of stem cells utilizing microcarriers: A biomaterials engineering perspective from academic research to commercialized products. Biomaterials. 2018 [accessed 2022 Nov 28];181:333–346. https://www.sciencedirect.com/science/article/pii/S0142961218304939. doi:10.1016/j.biomaterials.2018.07.016
    • ]]>     2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286420     Search Methodology & Source of Reviewed Literatures rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286421 The literature searched containing both the key words of microcarrier and bioprinting are searched in 3 major databases: Proquest, Pubmed, and Embase. Two categories of literature are searched, which are the application of microcarriers in bioprinting, and the application of microcarrier-based bioprinting in personalized medicine.]]> 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286421 Introduction rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286423 2022-11-29 03:43:18 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401286423 Overview & Methodology of Literature Review rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401291752 2022-11-29 03:49:47 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401291752 Result: Microcarrier Technology in Cell Expansion rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401304775 2022-11-29 04:05:46 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401304775 Factors Influencing the Cell Growth on Microcarriers rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401315840 There are four major chemical and biophysical properties of microcarriers that influence their ability to attach cells:
    • chemical composition
    • surface morphology
    • degree of porosity
    • charge density 
    These factors make the microcarriers a highly versatile and personalizable platform for cell culture,  as their properties can be altered to suit the type of cell culture, which is a huge advantage over 2D cell culture.  

    ]]>     2022-11-29 04:20:12 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401315840     Limitations and Considerations for Microcarrier-Based Bioinks rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401323783
  • The delivery of microcarriers through commercial bioprinters and assembling of the particles in 3D - Currently, hydrogels are used as delivering mediums for microcarriers, but they are not able to maintain the 3D structure of microcarrier particles.
  • Degradation of the microcarriers and the end products may have potential toxicity to cells (e.g. inflammatory response).
    • ]]>     2022-11-29 04:30:04 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401323783     Applications of Microcarriers in Personalised Medicine rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401338815 2022-11-29 04:46:17 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401338815 Conclusion rubyhe2 https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401345066 The Microcarrier technique is a promising solution for cell expansion for the scaling-up of  3D bioprinting, which not only helps generate sufficient cells for 3D printing but also guides specific cell differentiation. The chemical and biophysical properties of microcarrier particles should be considered to facilitate efficient and safe cell expansion,  including surface morphology, porosity, charge density, chemical composition, size, and polydispersity. 
    In the future, microcarrier techniques may help generate reliable and accurate human tissue models with complex structures to apply in drug screening and disease modeling. With the improving culture techniques like microcarriers, 3D printing technology is highlighted the potential of such therapies in the field of personalised medicine, with one of the explored therapies being bone regeneration for osteopathic conditions like arthritis. The techniques used in that therapy can be implemented to other cell types, as well which is a major advantage of this methodology.  The aim is to provide alternative therapies for major problems like organ shortages and tissue rejection in the future. ]]>     2022-11-29 04:51:51 UTC https://padlet.com/rubyhe2/vrwckriyrneletxr/wish/2401345066