Spraybase is being used in research to advance the development of electctrospun polymer dressings which protect, supply, and generally control the wound healing process.*
The Wound Dressing
Whenever our tissues are damaged, the surrounding cells, and the body as a whole, undergo a complex sequence of biological routines, which interact to limit damage, prevent infection, and faithfully reconstruct damaged tissue. A good wound dressing will treat exposed tissues gently, block out harmful microbes, aand allow the free flow of gases and fluids; but an ideal wound dressing will additionally create a chemical envrionment which moderates the wound’s cells to heal the tissue speedily and effectively.
Such a wound dressing is currently being developed by a largely German-based team1 who are investigating an interesting synergistic effect between retinol (also known as Vitamin A) and amorphous calcium poly-phosphate, which is released by blood platelets. Spraybase’s rotating drum collector was used to examine to collect these active agents through a gas-permeable poly lactide and poly ethylene glycol wound dressing, in a form that cells can easily interact with.
The Agents and Their Form.
Retinol has attracted attention in wound healing for some time. It is present in wounds, and exerts a strong, yet measured influence over the regrowth of cells and their scaffolds. For instance, retinol causes many cell types to multiply, including scaffold-producing fibroblasts, but it also reduces the quantity of ECM produced by a given fibroblast. This way, retinol maintains quality in the new scaffold, whilst minimizing scarring effects2. Like many possibly beneficial therapeutics, retinol has proven difficult to deliver: pure retinol delivered in solution was shown to be ineffective in this study1. Moreover, unless it is brought directly into contact with the affected cells, retinol tends to be metabolised into substances that are not desireable in wound healing3. Therefore, in order to be delivered for wound healing, the retinol needed to be packaged in a cell-friendly fashion.
Amorphous calcium poly-Phosphate was studied for three main reasons. It is an anti-bacterial; it appears to be very important in breaking down ruptured tissue scaffolds, and in blood clotting5, although the exact mechanism for this is the subject of debate4. It may additionally facilitate the actions of retinol, because as bound strings or clusters of appoximately 30 phosphate ions, the amorphous polyphosphate is readily taken into cells6.
In the study, the most successful form within which to co-deliver poly-phosphate and retinol proved to be a 200-350nm nanosphere made up of c. 90% calcium poly-phosphate and 10% retinol. These structures were produced by precipitating out calcium poly-phosphate in the presence of retinol over three days. These structures were then incorporated into poly-lactide and ethylene glycol solution (both degradable, biocompatible polymers). Some some samples of solution were additionally enriched with molecular retinol.
These solutions were electrospun and collectred using Spraybase’s rotating drum collector, into a porous, gas-permeable mat of 3µm fibers, embedded with these therapeutic nanospheres. Spraybase proved well able to handle this, and the several other tested solutions, producing plenty of consistent fibers for further study. The fibers were cut up, placed in wells, and seeded with cells in vitro.
To test whether these materials might promote a healthy healing process, the researchers checked whether the cells were behaving as they ought for an effective healing process with minimal scarring.
- They assessed how each fiber type moderated the growth and proliferation of cells.
- They interpreted the changing concentration of leptin, a fat-regulation hormone which is known to be momentarily upregulated in healing tissues7, and moreover to be necessary for wound healing in mice8.
- Additionally, they measured the production of Fatty Acid Binding Protein 4, which is also associated with improving the motility of replacement cells during the healing process9.
Retinol-enriched polyphosphate nanospheres, encapsulated in poly-lactide fibers, and electrospun by Spraybase’s spinneret proved the most effective: these dressings were richly proliferated with seeded cells.
There is more progress to be made before such bioactive dressings become routine in the treatment of chronic wounds. The team intend to investigate how to better control the degradation rate of these structures; determine exactly how they influence the cellular uptake of retinol; and investigate methods with which to stabilise the calcium poly-phosphate component of the treatment.
- W.E.G Müller, et al. Biochemistry and Biophysics Reports 3, (2015) 150-160. doi: 10.1016/j.bbrep.2015.08.007
- M. Abrigo, et al. Macromol. Biosci. 14 (2014) 772-92. doi: 10.1002/mabi.201300561
- Bailly, J., et al. Experimental dermatology 7.1 (1998) 27-34. doi: 10.1111/j.1600-0625.1998.tb00299.x
- Smith SA, et al. Proc Natl Acad Sci USA 103(4) (2006) 903-908. doi: 10.1073/pnas.0507195103
- L. Faxälv, et al. Blood 122 (2013) 3818-3824. doi: 10.1182/blood-2013-05-499384
- W.E.G. Müller, et al. Materials Lett. 148 (2015) 163-166. doi: 10.1016/j.matlet.2015.02.070
- Murad, Ali, et al. The FASEB journal 17.13 (2003) 1895-1897. doi: 10.1096/fj.03-0068fje
- Friedman, Jeffrey M., and Jeffrey L. Halaas. "Leptin and the regulation of body weight in mammals." Nature 395.6704 (1998) 763-770. doi: 10.1038/27376
- Y. Kusakari, et al. Mol. Cell. Biochem. 284 (2006) 183-188. doi: 10.1007/s11010-00509048-8