The present and future of tissue engineering 

By Pia Skok

Tissue engineering is a rapidly evolving field, aiming to repair, replace, or regenerate damaged tissues. By combining cells from the body with highly porous scaffold biomaterials, which act as templates interacting with the cells and influencing their behaviour, it enables new tissue growth.1  

There are two main approaches which are currently utilized to produce engineered tissues. First, scaffolds can be built from scratch from different biomaterials including ceramics, synthetic polymers, and natural polymers 1. Upon introduction of cells with or without the growth factors into the scaffold, they lay down a matrix to produce the foundations of a new tissue. The second approach involves using an existing scaffold which is formed when the cells of a donor organ are stripped, and a collagen scaffold remains.2 The approach utilized depends on what the subsequent use of the engineered tissue is, what biomaterial is used to build the scaffold and the source of cells.3 

Currently, tissue engineering plays a very important role in studying human physiology in vitro. So called organoids, the in vitro biological complexes with 3D structures that contain one or more cell types and that partially recapitulate the structure and function of their in vivo counterparts, provide a powerful way to study molecular mechanisms that underpin the function and dysfunction of different tissues.4 Before the development of organoids studies were performed on 2D cultures, where cells grown under non-physiological conditions and thus do not recreate properly in vivo systems in terms of cellular communication. Although animal models can display these complex cellular interactions, it is much better to use organoids as they capture human responses specifically. In addition, organoids are used to model and study the molecular mechanisms underlying human diseases. This allows the development of drugs and therapies as well as determine their effect on the tissue.5 So far organoid models for skin, brain, kidney, blood vessels, lung, stomach, and other organs have been engineered, each enabling us to understand how the organ functions and to develop treatments that tackle diseases associated with it. For example, brain organoids are being utilized to model ZIKV infection and psychiatric diseases, while kidney organoids are generated for personalized disease modelling such as BK virus infection, cystic fibrosis, and polycystic kidney disease.4 Multiple organoids are also used to provide an overview of cancer including how cancerous cells interact with each other and with the surrounding tissues. This greatly increases our understanding of the disease, and thus facilitates drug screening and development of cancer therapies.6  

In contrast to its significant role in research, tissue engineering currently plays a very small role in healthcare and patient treatment. Supplemental bladders, small arteries, skin grafts, cartilage, and full trachea have been engineered and implanted in patients, but the procedures are still experimental and very costly. For example, engineering an artificial skin substitute in vitro to replace and regenerate damaged skin after significant skin injury is still in experimental phases.7 However, it would address the problems of current autografts and allografts, which include increased morbidity and limitation of supply respectively.6  

In contrast, more complex tissues like heart, lung, and liver tissue have been successfully recreated in the lab, but they are a long way from being fully reproducible and ready to implant into a patient.2 The successfully generated organoid models that are currently being used in research need further optimization to generate more mature and complex structures that would be needed to replace real organs. At present, there are still many drawbacks associated with organoids, including the limited maturity and cell diversity when considered to replace the in vivo organs, the unsuitable size for organ transplantation, the poor reproducibility for massive production and the deficiency of the vascular, nervous, and immune system to imitate the in vivo tissue interaction.4 When these challenges are addressed the potential applications in healthcare are tremendous.  

Tissue and organ shortages have been identified as a major public health challenge with the demand for organs highly exceeding supply resulting in only a small percentage of deserving patients receiving transplantations.8 In addition, even the organ transplants that do occur are not always successful with approximately 50 percent of all transplanted organs being rejected within 10 to 12 years.9 These challenges often cannot be addressed by mechanical devices, which are not capable of accomplishing all the functions associated with the tissue and cannot prevent progressive patient deterioration, or surgical reconstruction, which can result in long-term problems. By developing artificial organs in vitro that would replace damaged ones in vivo, tissue engineering would provide more definitive solutions to tissue repair and organ transplants which we currently face.5   

With rapid advancement in the field of tissue engineering in the last decade, it is just a matter of time before these potential future applications become reality and transform the biomedical field. From helping us develop drugs and treatments for various diseases to replacing damaged organs, tissue engineering will allow us to significantly improve the quality of life. By offering new approaches to address health and longevity, it will enable us to live healthier and longer lives.  

References: 

  1. O’Brien, F. J. 2011. Biomaterials & scaffolds for tissue engineering. Materialstoday. 14 (3), 88-95. [online]. [Accessed 10th Sep 2021]. Available at: https://www.sciencedirect.com/science/article/pii/S136970211170058X 
  1. NIH. n. d. Tissue Engineering and Regenerative medicine. [online]. [Accessed 10th Sep 2021]. Available at: https://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine 
  1. Howard, D. et al. 2008. Tissue engineering: strategies, stem cells and scaffolds. Journal of Anatomy. 213 (1), 66-72. [online]. [Accessed 20th Sep 2021]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475566/ 
  1. He, J. et al. 2020. Organoid technology for tissue engineering. Journal of Molecular Cell Biology. 12 (8), 569–579. [online]. [Accessed 20th Sep 2021]. Available at: https://academic.oup.com/jmcb/article/12/8/569/5816289?login=true 
  1. Castells-Sala, C. et al. 2013. Current Applications of Tissue Engineering in Biomedicine. [online]. [Accessed 30th Sep 2021]. Available at: https://www.omicsonline.org/current-applications-of-tissue-engineering-in-biomedicine-2153-0777.S2-004.php?aid=16466 
  1. Bregenzer, M. E. et al. 2019. Integrated cancer tissue engineering models for precision medicine. [online]. [Accessed 1st Oct 2021]. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216564 
  1. Sierra-Sanchez, A. et al. 2021. Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries. npj Regen Med. 6 (35). [online]. [Accessed 1st Oct 2021]. Available at: https://www.nature.com/articles/s41536-021-00144-0 
  1. Dzobo, K. et al. 2018. Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine. Stem cells International. vol. 2018, article ID 2495848. [online]. [Accessed 1st Oct 2021]. Available at: https://www.hindawi.com/journals/sci/2018/2495848/#abstract 
  1. Synett-Pittsburgh, L. 2017. The first thing bodies do to reject a donor organ. [online]. [Accessed 1st Oct 2021]. Available at: https://www.futurity.org/organ-transplant-rejection-1472132-2/ 

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