Scaffolds in tissue engineering

What are scaffolds in tissue engineering?
Tissue engineering along with regenerative medicine can be used to create ‘Scaffolds’ in the human body. These scaffolds are used to support organs and organ systems that may have been damaged after injury or disease. So what is tissue engineering? ‘Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physico-chemical factors to improve or replace biological functions’. This is most commonly achieved through the use of stem cells. Stem cells are unique types of cells that are undifferentiated. They have the ability to differentiate to any type of specialized cell. They are most commonly found in embryos formed in the blastocyst phase, and are therefore known as embryonic stem cells. Also, they can be found in adult tissue, and are known as adult stem cells. So the main focus of creating these constructs is to be able to safely deliver these stem cells, and create a structure that is physically and mechanically stable so that these stem cells can differentiate.

Requirements scaffolds must fulfil in their purpose
There are two main types of ways scaffolds in tissue engineering can be achieved.
 * Allow cell attachment and migration
 * Deliver and retain cells and biochemical factors
 * Enable diffusion of vital cell nutrients and expressed products
 * Exert certain mechanical and biological influences to modify the behaviour of the cell phase

Injectable tissue engineering
Injectable tissue engineering can be used as an invasive procedure that involves injecting stem cells with a biomaterial into an organ such as the Heart that can form a gel in-situ. A gel in- situ is a soluble liquid which contains the stem cells and various biomaterials, once injected into the body, it will solidify and form a gel that acts as a scaffold to keep the structure of the organ in place. The stem cells will then differentiate into the required cells (mostly muscle cells such as myocardium), and replace the muscle tissue that had been destroyed previously due to any diseases etc. There are various different biomaterials that can be injected into organs in the body; each one has certain advantages and disadvantages. These biomaterials include: Fibrin, Alginate, Matrigel, Collagen and Chitosan. Biomaterials that are injected do not have to carry stem cells. They may be injected with other chemical components that show improvements in organ function post – injection.

Engineered constructs using invasive techniques
Fundamentally, this process involves the in vitro construction of a patch (or a graft). This patch is made from a combination of stem cells and an artificial extracellular matrix (biomaterial). The engineered patch can then be surgically implanted into affected areas of the body that need reconstruction. This procedure is very controversial in terms of ethics and also patient satisfaction. This is mainly because this technique is very invasive compared to other techniques that can be used alternatively. However, it does have many advantages. Firstly, the cells are all distributed evenly across the matrix. This ensures that stem cell clusters are not formed. Secondly, differentiation of these stem cells can take place in vitro. This is convenient because the differentiation occurs in a controlled environment. This ensures that stem cells aren’t wasted, and also that there are no mistakes in the differentiation process. For example, red blood cells being formed instead of cardiomyocytes.

Why are biomaterials used in scaffolds?
The importance of biomaterials can be highlighted when investigating how stem cells will fare when injected a specific area of an organ alone. The results are quite surprising; this is because retention of these cells by the human body is very low. Once injected, a large number of stem cells immediately leave the area. This is mainly due to the viscoscity of the suspension containing these cells. High viscoscity is a vital property any injectable solution must have, studies have shown that high viscoscity increases retention of cells. This is why the use of biomaterials are more favourable than injecting stem cells alone, they not only increase viscoscity but some biomaterials can form hydrogels which are responsive to certain biological signals such as temperature and salt concentrations. Furthermore, it has been proved that biomaterials that have anti-inflammatory properties also increase the long-term survival of stem cells. This strengthens organ function, as more stem cells will be able to differentiate into the specialised cells that are essential for organ function.

Controlling biodegradation and porosity of scaffolds
Over time scaffolds in the human body must degrade. They must remain in the organ until all the cells that are delivered become fully integrated. However, they should not linger long enough so that they hinder organ function. A simple solution to this is biodegradability. If the biomaterial used can degrade, then it satisfies all the above necessities a biomaterial should fulfil. When degrading, it should not produce any toxic residue or fumes, and it should also degrade at a suitable and controlled rate. Porosity is also an essential factor. Biomaterials with large inter connected pores are beneficial as they promote colonisation. However, pores that are too big can be detrimental to vascularisation, as endothelial cells will not be able to bridge across them.

There are many different ways scaffolds can be made so that they have a porous structure. These include:
 * Nanofiber Self-Assembly
 * Textile technologies
 * Solvent Casting & Particulate Leaching (SCPL)
 * Gas Foaming
 * Emulsification/Freeze-drying
 * Thermally Induced Phase Separation (TIPS)
 * Electrospinning
 * CAD/CAM Technologies

How is mechanical integration achieved?
An essential part of tissue engineering is the process of integration into its surrounding environment. Cells need to be arranged in such a way that they are connected to the vasculature, so that they have a good blood supply and are able to survive as long as possible. Therefore, biomaterials that show signs of angiogenesis will be favourable, as they can increase the integration of the injected cells. Increased integration into an organ will no doubt improve organ function in the long term.