A new study published on 8 January in Advanced Materials has presented a novel biomaterial with the unique ability to enable cell-selective activation of growth factors ― signalling proteins that control cell activities and therefore, tissue regeneration (1). The biomaterial ‘scaffold’ communicates with the body’s natural repair systems to promote wound healing.
The scientists from Imperial College London were able to recreate the natural healing process by using molecules called traction force-activated payloads (TrAPs), which allow scaffolds to actively communicate with cells in the body and provide key instructions that can improve wound healing. Furthermore, TrAPs were shown to interact with the correct cell type at the correct point in time during the wound repair process.
Tissue-engineered scaffolds are designed to interact with the body to promote tissue growth and repair. Some biomaterials are designed to release biological agents, such as various growth factors and proteins involved in tissue remodelling. However, these ‘bioactive’ scaffolds are often externally activated by stimuli such as light, enzymes, or pH, or a combination of multiple stimuli, which trigger the release of these bioactive components to aid in tissue regeneration.
The new scaffolds incorporate nano-sized TrAPs or ‘oligonucleotide aptamers’. The TrAPs are man-made single‐stranded DNA or RNA molecules folded into three-dimensional shapes known as aptamers that can be specifically designed to tightly bind to any protein ― in this case, growth factors. The researchers also added a customisable ‘handle’ that only allows certain cell types to grab hold. So, instead of requiring an external stimulus, such as light or an enzyme, these tiny molecules can actually sense the traction forces generated cells. In addition, the TrAPs will only allow the right cell type to attach.
The natural wound healing process involves many cells types, which navigate through the damaged tissue at different times while gradually remodelling the surrounding collagen the and extracellular matrix. By altering a TrAP’s so-called cellular handle ― effectively changing which type of cells can attach to ― the researchers were able to tailor the release of specific therapeutic proteins contained within the scaffold based on which cells were present at that time.
In their study, TrAPs were incorporated into scaffolds as a trigger to release a particular set of growth factors involved in wound healing ― thus creating ‘autonomous’ biomaterial scaffolds. The authors demonstrated that once the right cells type attaches to a TrAP, it unravels and releases the hidden growth factor, which provides key instructions to the surrounding cells on how to grow and multiply.
The TrAPs are relatively straightforward to make in the lab and can be scaled up to clinically-relevant quantities. Furthermore, they are currently used as drugs, therefore, the path to clinical use could be much shorter since they are already proven to be safe in humans. In addition, the flexibility of these molecules could allow them to be used for studying human disease and tissue development in the lab.
This is the first time scientists have achieved the release of specific growth factors from a scaffold depending on its interaction with a particular cell type. This cell-specific release of proteins mimic the natural healing process and could be used for a wide range of injuries from fractured bones to heart attacks.
(1) Stejskalová, A. et al. Biologically Inspired, Cell‐Selective Release of Aptamer‐Trapped Growth Factors by Traction Forces. Advanced Materials (2018). DOI: 10.1002/adma.201806380
Image: Skin cells (fibroblasts) involved in wound healing. Getty Images.