# data[].attributes.body
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.

# data[].attributes.headline
Applications of Microcarriers in Personalised Medicine

# data[].attributes.subject
Applications of Microcarriers in Personalised Medicine

# data[].attributes.attachment_caption
A specially designed microcarrier particles to test the potential toxicity of the microcarrier and the inflammatory respond towards it. Go et al. 2021

# data[].attributes.body
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).

# data[].attributes.attachment_caption
 Different shape of microcarriers are used in commercial products. Tavassoli et al. 2018

# data[].attributes.headline
Factors Influencing the Cell Growth on Microcarriers

# data[].attributes.subject
Factors Influencing the Cell Growth on Microcarriers

# data[].attributes.body
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.

# data[].attributes.headline
Result: Microcarrier Technology in Cell Expansion

# data[].attributes.subject
Result: Microcarrier Technology in Cell Expansion

# data[].attributes.headline
Overview & Methodology of Literature Review

# data[].attributes.subject
Overview & Methodology of Literature Review

# data[].attributes.body
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

# data[].attributes.attachment_caption
From university lab group to award-winning star-up.

# data[].attributes.body
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.

# data[].attributes.attachment_caption
Fibrin-based neurobioink in research and development. Picture from Brinter.com

# data[].attributes.headline
The core of Axolotl: Bioprinting in the Field of Tissue Engineering and Regenerative Medicine

# data[].attributes.subject
The core of Axolotl: Bioprinting in the Field of Tissue Engineering and Regenerative Medicine

# data[].attributes.body
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.

# data[].attributes.body
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.

# data[].attributes.attachment_caption
Microcarrier beads covered in cells under electron microscopy. Picture from fineartamerica.com

# data[].attributes.body
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).

# data[].attributes.attachment_caption
Morphology of Mesenchymal Stem Cells 4 h after mixing with cell-free microcarriers. Levato et al. 2014

# data[].attributes.headline
Recent Advance in Bioprinting Using Microcarriers

# data[].attributes.subject
Recent Advance in Bioprinting Using Microcarriers

# data[].attributes.body
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.

# data[].attributes.attachment_caption
Fluorescent images of MSCs attached on microcarriers over 14 days dynamic culturing (Dashtimoghadam et al. 2020)

# data[].attributes.headline
Case study for Microcarriers in Personalized Medicine

# data[].attributes.subject
Case study for Microcarriers in Personalized Medicine

# data[].attributes.body
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.

# data[].attributes.headline
Importance of Personalized Medicine using Microcarriers

# data[].attributes.subject
Importance of Personalized Medicine using Microcarriers

# data[].attributes.body
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

# data[].attributes.headline
Potential Areas of Personalized Medicine to Harness Microcarriers

# data[].attributes.subject
Potential Areas of Personalized Medicine to Harness Microcarriers

# data[].attributes.body
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.

# data[].attributes.attachment_caption
Human iPS Cells differentiated into different cell types which formed teratomas (Takahashi et al. 2007)

# data[].attributes.body
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.

# data[].attributes.body
1. Common cold can be surprisingly dangerous for transplant patients. 2017 Mar 7. Fred Hutch. [accessed 2022 Nov 18].

2. https://www.fredhutch.org/en/news/center-news/2017/03/common-cold-can-be-surprisingly-dangerous-for-transplant-patients.html.

3. 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.

4. 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

5. 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

6. HRSA. 2022 Mar. Organ Donation Statistics | organdonor.gov. wwworgandonorgov. https://www.organdonor.gov/learn/organ-donation-statistics.

7. 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.

8. 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

9. 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.

10. 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

# data[].attributes.attachment_caption
Keywords for three databases and literature search results

# data[].attributes.headline
Search Methodology & Source of Reviewed Literatures

# data[].attributes.subject
Search Methodology & Source of Reviewed Literatures

# data[].attributes.body
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.