ETRS Young Investigator Award Winner
Thermosensitive Biomimetic Polyisocyanopeptide Hydrogels May Facilitate Wound Repair
Roel Op 't Veld, Hans Von Den Hoff, Onno Van Den Boomen, Ditte Lundvig, Ewald Bronkhorst, Paul Kouwer, John Jansen, Frank Wagener, Alan Rowan
Radboud University Medical Centre, Gelderland, Netherlands
Following wounding, a complex cascade of events is initiated to stop blood loss, to eliminate invading pathogens, and ultimately, to promote tissue integrity and homeostasis. However, when wound repair is interrupted severe fibrosis and scar formation can occur. Since wound dressings need to be changed regularly, this results in "ripping open" the wound area, which is painful and hampers tissue regeneration. Unfortunately, the current wound dressings are not ideal. Recently, a novel poly-isocyanopeptide (PIC) hydrogel has been developed that is thermosensitive and could facilitate in safer and painless dressing renewal. The material is liquid at cold temperatures, and gelates when temperature rises (> ~16°C). It possesses unique strain stiffening capabilities that are also similar to the natural extracellular matrix. We postulated that both this synthetic PIC hydrogel and RGD-functionalized PIC hydrogel allow normal wound repair without excessive cytotoxic or pro-inflammatory complications in full thickness wounds in the dorsal skin of mice.
We demonstrated the functionalization of PIC polymer side-chains with RGD peptides through click-chemistry. Following application of the cold liquid PIC dressings onto the wound, it immediately gelated, covering it completely. Wound closure was not hampered by the PIC hydrogels and not changed when compared to wounds without gel. No giant cells were present in wounds with or without the synthetic gel. Moreover, no inflammatory or fibrotic reactions were evoked by the biomimetic synthetic gel as we demonstrated no increase in macrophages, myofibroblasts, collagen formation, or angiogenesis. By contrast, a small but significant decrease in granulocyte recruitment was observed. Addition of RGD did not result in further changes in inflammatory cell recruitment. The observed decrease in granulocyte influx following hydrogel application is likely related to decreased bacteria influx, because the nanosized pores of the gel prevent entry. The biocompatibility and absence of adverse effects makes this tunable hydrogel highly suitable for development into a wound plaster and for targeting the different phases of woundrepair.
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