Threads of discovery: Nobel laureates weaving the tapestry of tissue engineering

Written by Felix Myhill (Assistant Editor)
News Tissue engineering or replacements
Nobel prize, Tissue engineering

One of the primary goals of tissue engineering is the production of functional tissue constructs; however, generating viable constructs is incredibly difficult – owing to the intricate nature of tissues themselves. Due to this intricacy, it is perhaps no surprise that on several occasions, researchers awarded a Nobel Prize – one of the most prestigious awards that a scientist can receive – have been involved in broadening tissue engineering’s horizons. In this listicle, we will explore how several Nobel laureates have molded the field of tissue engineering. 

Alexis Carrel

Carrel (The Rockefeller University; NY, USA) was awarded the 1912 Nobel Prize for Physiology or Medicine for his pioneering work in blood vessel suturing and organ transplantation [1]. While transplantation is critical to the eventual goal of using functional tissue constructs in clinical application, his non-Nobel prize-winning research of ex vivo endothermal animal cell expansion [2] laid the foundations of modern cell culturing.

Cell culturing underpins every facet of tissue engineering and has evolved increasingly advanced methods, culminating in modern-day three-dimensional, four-dimensional and microfluidic culture systems, which are more replicative of native tissues and tissue systems [3].

John Gurdon and Shinya Yamanaka

Gurdon (University of Cambridge, UK) and Yamanaka (Kyoto University, Japan) were jointly awarded the 2012 Nobel Prize for Physiology and Medicine for their discovery that mature cells could be reprogrammed to become pluripotent. The resultant cells coined induced pluripotent stem cells (iPSCs) [4], expanded and strengthened the toolset of cellular biology.

iPSCs are crucial for tissue engineering, which requires a large supply of cells that can be differentiated into specific cell types for functional tissue constructs. iPSCs circumvent the ethical concerns of embryonic stem cells while possessing pluripotency and self-renewal capacity, making them ideal for generating functional tissue constructs [5]. As they can be generated from an autologous source, they also reduce the likelihood of immune rejection of a clinical tissue construct [6].

Arthur Ashkin

Ashkin (AT&T Bell Laboratories; NJ, USA) shared the 2018 Nobel Prize in Physics for his invention of optical tweezers, a technique that exploits radiation pressure from lasers to trap particles and atoms. Ashkin found the optical tweezers to be capable of immobilizing cells, after a chance mistake where the experimental setup was left on overnight and had trapped freely suspended bacteria without damaging them [7].

Optical tweezers have been used to pattern induced pluripotent stem cell arrays [8], multicellular arrays of fibroblasts, myoblasts and neuroblasts [9,10] as well as microtubule arrays [11]. However, while they possess high spatial precision, they are currently confined by their low-throughput properties and require technological advancement to generate full-sized constructs [11]. They remain a promising technology for tissue engineering yet to be fully exploited.

Emmanuelle Charpentier and Jennifer Doudna

Charpentier (Max Planck Unit for the Science of Pathogens, Germany) and Doudna (University of California, Berkeley; CA, USA) were jointly awarded the 2020 Nobel Prize in Chemistry for their discovery of the CRISPR/Cas9 gene-editing complex [11]. Controlled reprogramming and transdifferentiation of cells can be achieved effectively with CRISPR/Cas9 silencing, as well as the technological derivatives such as dCas9 – which upregulates gene expression [12].

These technologies enable more efficient control of differentiation into a desired cell type as well as the enhancement of cells’ gene-directed regenerative capabilities. CRISPR technology can also be used to alter genes to reduce the likelihood of an immune rejection. Both of these aspects are important in fabricating functional tissue constructs [13].

Morten Meldal, Barry Sharpless and Carolyn Bertozzi

2022’s Nobel Prize in Chemistry was awarded to a tripartite of Meldal (University of Copenhagen, Denmark), Sharpless (Kyushu University, Japan) and Bertozzi (Stanford University; CA, USA) for their work in Click chemistry, a form of chemistry that facilitates quick reactions with a high-yield, while minimizing by-products. Click chemistry can be used can be used to join molecules together in a highly controllable manner. Meldal and Sharpless independently converged on the foundational chemical reaction, while Bertozzi took this technology a step further by performing click chemistry reactions inside living cells, which are exceedingly rare in nature, without disrupting their normal chemistry [14].

Click chemistry has improved the fabrication of polymeric scaffolds used in tissue engineering that better simulate the structure and function of native tissue, such as by improving oxygen supply, mechanical load-bearing properties, adhesion to native tissues, hemostasis, anti-inflammatory and anti-bacterial properties [15]. It has also contributed to the more efficient attachment of cells to scaffolds [16].

These Nobel laureates hail from different backgrounds – chemistry, physics and biology – and their discoveries have contributed to different technical areas, including spatial patterning, cell culturing and genome editing. However, they all elegantly converge and contribute to tissue engineering, unified by the goal of generating functional tissue constructs. As the collaboration across multiple disciplines continues to unravel tissue engineering’s complexities, a new, more detailed era of regenerative medicine, in which there may well be more Nobel laureates to follow, seems imminent.

This article is part of our Spotlight on tissue engineering 

Visit the Spotlight, produced in association with Cook MyoSite, to delve into the current landscape. It covers the breakthroughs, challenges, and exciting applications that are unfolding in the field.

Source

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