Silk Microsphere Encapsulation of Wound Healing Peptides for Regenerative Medicine.
- Chronic wounds are comorbid with diseases that are on the rise, such as diabetes mellitus and atherosclerosis, and as such present a growing problem to the medical community. Although there is a range of treatment options available, from hyberbaric oxygen treatments to tissue grafts, there has been an increasing interest in the use of bioactive peptides, specifically those involved in angiogenesis... read more, for the treatment of chronic wounds. In accordance with this, two peptides were developed in the Herman laboratory, UN3 and Comb1. UN3 is a peptide isolated from platelet releasate, whereas Comb1 is a combinatory peptide synthesized from the EGF-like domains of fibrillin 1 and tenascin X, two noncollagenous ECM peptides. Both of these peptides have been shown to stimulate angiogenesis in vitro. However, in order to facilitate controlled and predictable release of the peptides they were tested in a silk microsphere drug delivery system. This system has the benefits of being biocompatible and biodegradeable, undergoes processing under ambient conditions, and can be modified to change drug delivery rates. In this study, preliminary evaluations of the release profile of biotinylated-Comb1, FITC-Comb1, and UN3 from silk microspheres were performed, and the bioactivity of the peptides after they were released was assessed with an in vitro tube formation study. It was found that all three peptides showed a characteristic release profile that fit a logarithmic regression curve with high correlation, and that silk microsphere delivery was more efficient for FITC-Comb1 and botinylated-Comb1 than UN3. It was also shown in vitro that silk microspheres loaded with the angiogenic peptides stimulated significantly greater angiogenesis than the serum control at the seven hour time point, as measured by total tube proliferation. Future work should focus on conducting in vivo studies with the silk microsphere drug delivery system and in optimizing the microspheres for more sustained release.read less