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MATERIALS FOR CREATING TISSUES 

Some materials used to create tissues include cells, a scaffold, and growth factors. However, it isn't as simple as that. For each type of material, there are a variety of choices that scientists can make. The type of cells, the material used to create the scaffold, and the type of growth factors used can greatly affect how the end product turns out.  

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CELLS 

Autologous Cells

Autologous cells are cells where the donor and recipient are the same people. These cells are extracted using peripheral blood stem cell transplantation (PBSCT). These are the steps:

 

  • A mix of chemotherapy and a growth factor (called G-CSF) is inserted into the blood

  • The G-CSF causes the stem cells to spill into the blood, mixing the two together

  • The stem cells and blood are separated by a machine called a cell separator. The cell separator collects the stem cells, and return the blood to your bloodstream

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Diagram explaining the difference between autologous and allogeneic stem cell transplants  

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Allogeneic Cells

Allogeneic cells are cells where the donor isn't the recipient; it can either be a relative or complete stranger. These cells can be collected two ways:

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  • Bone Marrow Transplantation (BMT): These are the steps:

    • First, some of the liquid from the bone marrow is removed through a needle.

    • When enough stem cells are collected, they are put into a blood bag and frozen until they are used again.

  • Peripheral Blood Stem Cell Transplantation (PBSCT): This process is similar to autologous cells. 

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Diagram explaining the process of an allogeneic transplant through the perspective of a cancer patient 

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Mesenchymal Stem Cells (MSCs)

Mesenchymal stem cells (MSCs) are cells found in the bone marrow that can produce more than one type of cell. Some of the types they can produce include cartilage, bone, and fat cells. However, scientists are working on experiments to see if MSCs can produce other cells. They are also working on experiments for new treatments using MSCs. However, the latter is very recent. 

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Diagram showing the different types of cells MSCs can differentiate into   

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SCAFFOLDS

What is a Scaffold?

A scaffold is a framework that holds cells and tissues together. They are either made in vitro (taking place outside an organism) and then implanted or implanted directly and regeneration takes place in vivo (taking place inside an organism).

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When building a scaffold, there are many requirements, such as:

 

  • Biocompatibility: The scaffold, when placed inside of the body, must be able to co-exist peacefully with the cells around it. If it doesn't co-exist peacefully, it will cause a severe inflammatory response, hurting the patient.

  • Biodegradability: The material must be biodegradable, meaning it must be able to decompose. The cells must be able to produce their own scaffold, one that will eventually replace the implanted one. So it must be able to decompose so it will be replaced by the natural one. The material should also be non-toxic, so it can exit the body without causing any harm to internal organs.

  • Mechanical Properties: The scaffold should be able to function like the tissues around it, so it doesn't interrupt the process of the site around it. The scaffold should also be strong enough.

  • Manufacturing Technology: It should be inexpensive and easy to construct. It is also important to know how the scaffold will be delivered to any laboratory who needs it. This will determine how the scaffold will be stored.  

Scaffold Requirements

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Scaffolds can be made of many materials. The materials come from these three groups: ceramics, synthetic polymers, and natural polymers. Each group has its own uses, advantages, and disadvantages when it comes to creating a scaffold. 

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Ceramics

Ceramics such as hydroxyapatite (HAP) and tri-calcium phosphate (TCP) are used for making hard tissue, such as bone and teeth. Because of their brittleness, they aren't often used for soft tissue regeneration. 

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Details

However, there are a few disadvantages to ceramics. They have limited use because of their brittleness, lack of flexibility and new bone modeled in a HAP network can't be remodeled easily. 

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Details

 Some of the advantages of synthetic polymers include the fact that they can be remodeled easily and their degradation can be controlled to suit the need of the scientist working with the scaffold.

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Structure of the synthetic polymer PLGA

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Synthetic Polymers

Some synthetic polymers that have been used include:​​

  • Poly-l-lactic acid (PLLA)

  • Polyglycolic acid (PGA)  

  • Poly-dl-lactic-co-glycolic acid (PLGA) 

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Chemical structure of PLLA

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Natural Polymers

 Some natural polymers that scientists use include:

  • Collagen

  • Polysaccharides

  • Chitosan

  • Agarose

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Chemical structure of agarose

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Details

 Some advantages of natural polymers are that they promote cell growth and are biodegradable. However, one disadvantage they have is poor mechanical properties, which limits their use.  

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GROWTH FACTORS

What are Growth Factors?

Growth factors are proteins that promote growth in living cells. It does this by attaching itself to receptors on the target cell and sending a signal to the nucleus.  

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Diagram showing how growth factors help stimulate cell growth

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Growth Factors: What Makes Them Different?

The ability to deliver a certain message to a certain population of cells depends on many factors, such as:

 

  • The type of growth factor

  • The target cell number

  • Types of receptors

  • Ability to go through the extracellular matrices (ECM)

  • The signal transduction (set of chemical reactions that happens when a molecule attaches itself to a receptor) 

 

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Diagram showing how nerve factors work 

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Types of Growth Factors

Different types of growth factors include:

 

  • Basic fibroblast growth factor (bFGF)

  • Epidermal growth factor (EGF)

  • Fibroblast growth factor (FGF)

  • Nerve growth factor (NGF)

  • Transforming growth factor (TGF)

  • Vascular endothelial growth factor (VEGF)

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How are Growth Factors Used?

Growth factors are used in tissue engineering by seeding them onto scaffolds. There are two different ways to seed them onto a scaffold:

 

  • Non-Covalent: One method of non-covalent incorporation is by using biopolymeric gels. These gels, which consist of biomaterials, are used to immobilize growth factors. Though this may seem like it would stop cell growth, it actually doesn't. One biomaterial, fibrin, has been used to deliver growth factors to certain areas of interest. NGF (nerve growth factor) bound to a fibrin network has been shown to increase nerve regeneration.

  • Covalent: Another method is to covalently bond growth factors to polymer carriers. The factors perform normally and are slowly degraded. This method has many advantages, such as promoting cell growth. 

 

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