Despite the success of organ transplantation since its inception in the 20th century, people today are still losing their lives waiting for organs. The dependence of organ transplantation on human donors means that people must rely on the availability of a donor for their survival. However, advances in the field of tissue engineering may soon provide alternatives to organ transplantation. For example, bioactive inserts may make it possible to restore the function of a severely damaged organ, thus reducing the need for organ transplants.
What is tissue engineering?
To understand tissue engineering, we must first understand the nature of our bodies’ organs. An organ is made up of a series of tissues, which work together to perform the organ’s vital functions. The tissues themselves are each made up of two components: a cellular component (a group of similar cells with tissue-specific functions) and a non-cellular component, known as an extra-cellular matrix (ECM). The ECM provides structural support for the cells in the tissue, and influences their behaviour. When supported in this way, the cells regularly create fresh matrix material. Thus, the cellular and non-cellular components work together to regularly regenerate the tissue.
However, when the ECM of a tissue becomes damaged, the cellular component is often unable to regenerate the original matrix, and instead deposits scar tissue to repair the damage. Scar tissue often has inferior mechanical and biological functionality compared to the tissue which it has replaced, which can lead to a reduction in overall organ function. An extreme example of this occurs when the muscle of the heart becomes damaged as a result of a heart attack. The damaged muscle is replaced with scar tissue which leads to weakening of the heart and raises the risk of future heart failure.
The aim of tissue engineering is to generate healthy material which can be used to replace damaged tissues. One attempt at doing this involves providing a bioactive insert which mimics the ECM of the damaged tissue. When such an insert is seeded with appropriate cells, the cells proliferate and deposit healthy tissue as if they were performing normal tissue regeneration. This allows organs to be healed with healthy tissue instead of scar tissue, limiting any loss of function, and potentially avoiding the need for a transplant.
However, this application requires the inserts to have a wide range of properties. For example, the inserts must be biocompatible, biodegradable, have suitable mechanical properties, and must be able to appropriately interact with and influence the cellular component of a given tissue. There are therefore many limitations on which materials may be used for these inserts.
Collagen-based inserts
Given these limitations, the best materials for bioactive inserts may be those which naturally occur in human tissue. For example, collagen is an abundant tissue in extra-cellular matrices, and so possesses the necessary cell-influencing properties required of a bioactive insert. It is also biocompatible and biodegradable, and possesses good mechanical properties.
Scientists today are actively researching ways to use collagen in tissue engineering applications. For example, at the Cambridge Centre for Medical Materials, a particular arrangement of collagen is being investigated for use as a bioactive insert. The structure, known as a ‘collagen scaffold’, is a 3D porous network of collagen through which cells can permeate and perform their regenerative functions, and hence, when placed into a wound, allows fresh tissue to be deposited homogenously along the damaged tissue. Once the regeneration has occurred, the collagen scaffold is capable of degrading to leave only the repaired tissue.
The future of tissue engineering
Collagen scaffolds have already been used commercially for tendon and ligament repair, cartilage regeneration, and dermal grafts. However, further optimisation of collagen scaffolds is required before they can be applied to a full range of clinical applications. There are multiple avenues of research currently being explored to achieve this. For example, by changing the temperature gradients during the manufacture (freeze-drying) of the scaffolds, the arrangement of collagen in the final scaffolds can be altered. Therefore, by controlling these temperature gradients, the properties of the scaffold may be tailored to a specific tissue 1.
Additionally, scaffold properties can be customised by the addition of other materials such as elastin and hyaluronic acid. Also of interest is the use of crosslinking agents. Such agents can be added to crosslink the collagen fibres of a scaffold, thereby increasing its elastic modulus, and influencing its biological properties. Thus, the controlled use of such agents provides the potential for the mechanical and biological properties of collagen scaffolds to be fine-tuned to specific applications 1.
Based on these active areas of research, scientists may in the future be able to create personalised bioactive inserts, suitable for application in a wide range of human organs and tissues. This would vastly reduce our healthcare system’s reliance on organ donors, saving countless lives.
- Time for regeneration. Nair (2018). Materials World, Vol 26, No. 8, August 2018, p. 49-51.
Written by Dan Warburton.
