Scaffolds for Biological Tissue Reconstruction

In this post we'll be talking about scaffolds that can be used to grow cells and tissues for later implantation.

History

Apparently people have been using various sorts of implants for over 2000 years, but the more modern kinds of implants date back to the 1940s. In the 1940s, a British ophthalmologist found that fighter pilots whose eyes were injured by shards of canopy plastic didn't have any apparent reactions to the plastic, so he looked at the use of this plastic in eye implants. In the 1960s, materials for implants were more specifically designed and engineered.

Purpose

As I said at the beginning, scaffolds can be used to grow cells and tissues for later implantation. Bioscaffolds, cells, and growth stimulating signals are collectively known as the "Tissue Engineering Triad."

Functions

The function of a scaffold is to act as a synthetic ECM (extracellular matrix) so that cells can grow on them without any problems. Therefore, it needs to be able to perform some of the functions of ECM, including structural support, provision of bioactive cues for cell alignment, provision of growth factors, and provision of a changeable environment in which processes such as remodelling and neovascularisation (growth of new blood vessels) can take place.

Properties

In order to design an appropriate scaffold, we need to take several properties into consideration:

1. Architecture- This includes things like void volume (empty space), porosity, and biodegradability. Void volume may influence vascularisation and new tissue formation, while porosity may influence metabolite and nutrient transport. Ideally, the rate of degradation should match the rate of tissue formation.
2. Tissue compatibility- The scaffold must be non-toxic and allow cells to grow and differentiate on it.
3. Bioactivity- Ideally, the scaffold should be able to interact with cells and regulate their activities. This may be achieved through topographical features (mechanobiology, anyone?) or through the use of chemical signals.
4. Mechanical properties- The scaffold should provide some shape and stability. It may be helpful if the mechanical properties of the scaffold are similar to those of the host tissue.

Approaches to bioscaffold design

Pre-made scaffolds

One approach to bioscaffold design is simply to make a scaffold and seed cells on it later. Scaffolds can be made with natural or synthetic materials. Natural scaffolds can include substances like silk, collagen, alginates, etc., or even graft tissue. Natural scaffolds have excellent biocompatibility and cells attach to them easily, but they are relatively fragile. Synthetic scaffolds include a range of materials, such as glass, ceramics, nylon, or plexiglass. Synthetic scaffolds are not as biocompatible as natural scaffolds, but they allow for much greater control over their physical and mechanical properties.

Synthetic materials can be made using a variety of different methods, including electrospinning, casting, nanoweaving, and 3D printing. Electrospinning involves a probe tip that fires a liquid jet of polymer solution at a collector (okay, that was probably way oversimplified, but unfortunately that's all I really understood about this method). Casting involves the use of a mould. Nanoweaving is basically just weaving really small threads, and you've probably already heard of 3D printing, so I won't go into that.

Decellularised ECM

Decellularised ECM uses tissue derived from an allograft (graft from a member of the same species) or xenograft (graft from a member of a different species). The tissue is chemically treated to remove all of the cells, leaving only the ECM. Decellularised ECMs have excellent biocompatibility and are generally pretty functional, but there are also disadvantages. It is difficult to seed cells at an even distribution over a decellularised ECM, and if the ECM is not properly decellularised, there is a possibility of an immune reaction.

Cell sheets

This one is pretty much what it says on the box- cells are grown in sheets, which can be stacked on top of each other. The advantages of this method are that cells secrete their own ECM, the sheets are rapidly neovascularised (I think this means that new blood vessels supplying this area will rapidly develop) and no sutures are required during implantation. Disadvantages of this method include limited thickness (they aren't vascularised before implantation, so you're limited by diffusion), and are quite fragile.

Cell encapsulation

Cell encapsulation involves trapping cells in a solid ECM. This can be done by suspending cells in a liquid, and allowing the liquid monomers to self-assemble. This method is good for irregularly-shaped defects, but is also quite fragile.

Combination scaffolds

The above techniques can also be combined to make a combination scaffold.

Clinical Example

Our lecturer is working on developing a tympanic membrane (ear drum). His team is investigating the use of fibroin (a component of silk), which is biocompatible, fairly stiff, and able to be moulded. It is not, however, very biodegradable. The goal is to be able to culture cells on this membrane and implant it into a perforated eardrum in order to heal the perforation.