This week in lecture we discussed the benefits of using decellularization as a technique for making biomaterials. Decellularization is the process by which cells are removed so that only the extracellular matrix is left. This technique is beneficial because it means that there is a pre-made skeleton that is known to house cells that can be used. Therefore, when using decellularized tissue, you can add in new cells to fill in the pre-made network. This can be beneficial as it allows for the use of cells that will make the implantation of the material more successful.

In the experiment done in the paper, the researchers created a material to aid in wound healing. The material was composed of decellularized human skin tissue and human umbilical cord perivascular cells (HUCPVC). This specific cell type was chosen because it is a stem cell that is known to help in wound healing, specifically within the skin. The way these cells specifically are able to promote wound healing within the skin is because they promote the creation of neovascularization that will allow blood to reach the area of injury. Additionally, these cells do not cause a strong inflammatory response, which indicates that they can be used even when not taken directly from the patient. The paper conducted studies to identify if the scaffold created would be beneficial to use in order to deliver the HUCPVCs to the wound site.

For the experiments run, the researchers first had to be sure that all the native cells on the scaffold were fully removed. This is an important step because it could cause a negative inflammatory effect when inserted in the body if the original cells still remain. Additionally, it is important that the only cells that are focused on are the HUCPVSs rather than another cell present in the scaffold. The next step was to ensure that the HUCPVS cells were able to attach to the scaffold and remain alive, and this proved to be successful. The biomechanical properties of the material with and without the cells were also tested. This test indicated that the present cells did not affect the biomechanical properties. Once, these tests were conducted, it was then safe to move on the in vivo experiments.

For the in vivo experiments, a diabetic rat model was used because it best exemplifies chronic wounds. A control for the experiment included the same wound, but using no material for the healing process. The researchers also tested the scaffold without the cells added, and then another model used the combination of the scaffold with the HUCPVC cells added to it. A figure of the results after 0, 7, 14, and 21 days is shown below.

What the researchers found was the wound that was treated with the combination of the decellularized skin scaffold and the HUCPVS cells had the most promising results because a higher percentage of the wound closed.  More in depth analysis showed that there was more collagen deposited at the area of the wound with the model that had the scaffold and cells. This indicates more matrix production that would aid in the wound healing process. Overall, this new biomaterial was shown to be very effective, and makes practical use of the decellularization process.

Milan, P. B., Lotfibakhshaiesh, N., Joghataie, M. T., Ai, J., Pazouki, A., Kaplan, D. L., … & Samadikuchaksaraei, A. (2016). Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells. Acta biomaterialia, 45, 234-246.

Now that we have finished covering polymers, ceramics, and metals, we have started to focus on composites. Composites are made up of multiple of materials. In the case of the device I am reviewing, the material is a hydrogel that is composed of both bioglass and agarose-alginate(AA).

The material in the article is a hydrogel and is used as an innovative dressing for wounds. As I’ve discussed in previous blog posts, chronic wounds are a major rising issue especially with the influx of people with diabetes. The body’s inability to repair itself leads to chronic wounds, therefore new materials try to aid the wound healing process This particular material attempts to do this by addressing the humidity at the wound site and also by increasing the ability of angiogenesis.

The material makes use of bioglass’ ability to aid wound healing by promoting angiogenesis, and AA’s ability to create a humid environment. As we learned in lecture, composite materials will not merge together, but instead the composite will have a mixture of properties of the used materials, which in this case would be ceramics and polymers. For this reason, bioglass and AA should both have the same effect that they normally have within the body. However, these materials will work together because the moist environment created by AA allows for the bioglass to release bioactive molecules that will improve the process of creating new blood vessels. If blood is able to effectively flow to the wound site, then there is a higher probability of the wound healing.

The in vivo experiment tested the material at different ratios of agarose and alginate on a rabbit ear’s wound, and it was seen that the models with bioglass and AA performed better (figure shown below). The conclusion was that since more endothelial cells and fibroblasts migrated to the area and due to the increased humidity, then the body was able to heal at a more rapid pace.

When deciding what materials to use, the researches mentioned that although bioglass has useful properties, it is normally used in a powder form which can be difficult to use for a wound site. They were able to fix this issue by combining it with AA, which can make the material temperature dependent for gelation, and thus a material that is both injectable and can solidify at a wound site as need was created.  Ultimately, different materials have their own individual advantages and disadvantages; however, composite materials are able to combine the best aspects of multiple materials to create new biomaterials with the most ideal characteristics.

Zeng, Q., Han, Y., Li, H., & Chang, J. (2015). Design of a thermosensitive bioglass/agarose–alginate composite hydrogel for chronic wound healing. Journal of Materials Chemistry B, 3(45), 8856-8864.