Search

Wounds often result in scarring, prolonged morbidity, and loss of function. New interactive and modifiable hydrogel wound dressings are being developed for these injuries. Polyisocyanopeptide (PIC) gel is a promising thermosensitive hydrogel having several characteristics that can facilitate wound repair, including ease of application/removal and strain-stiffening properties that mimic extracellular matrix components. However, it is unknown whether the PIC gel remains in the wound for a clinically relevant time period. Therefore, PIC polymers were functionalized with a DTPA group allowing labelling with Indium-111 ( 111 In). Following application of this radiolabelled gel to splinted and non-splinted murine full-thickness skin wounds the signal was monitored using SPECT/CT imaging for 7 days. The SPECT signal from the PIC gel was highly stable and covered the complete wound area. Non-bound 111 In-EDTA was rapidly cleared via the kidneys to the urine. The impact of PIC gels on wound repair was further studied visually and histologically. Radiolabelled PIC gel was observed to move both over and under the skin, while histological analysis demonstrated that part of the gel became encapsulated within the wound repair tissue, but did not delay wound closure or otherwise impair wound healing. This work illustrates for the first time the use of 111 In-labelled PIC gels for diagnostic and monitoring purposes and describes the use of PIC in the (non-)splinted murine skin wound model. It was found that PIC gels remained in splinted and non-splinted full-thickness skin wounds during wound repair. This warrants the continuation of developing the PIC gel into a clinically advanced wound dressing.

Changing wound dressings inflicts pain and may disrupt wound repair. Novel synthetic thermosensitive hydrogels based on polyisocyanopeptide (PIC) offer a solution. These gels are liquid below 16 °C and form gels beyond room temperature. The architecture and mechanical properties of PIC gels closely resemble collagen and fibrin, and include the characteristic stiffening response at high strains. Considering the reversible thermo-responsive behavior, we postulate that PIC gels are easy to apply and remove, and facilitate healing without eliciting foreign body responses or excessive inflammation. Biocompatibility may be higher in RGD-peptide-functionalized PIC gels due to enhanced cell binding capabilities. Full-thickness dorsal skin wounds in mice were compared to wounds treated with PIC gel and PIC-RGD gel for 3 and 7 days. No foreign body reactions and similar wound closure rates were found in all groups. The level of macrophages, myofibroblasts, epithelial migration, collagen expression, and blood vessels did not significantly differ from controls. Surprisingly, granulocyte populations in the wound decreased significantly in the PIC gel-treated groups, likely because foreign bacteria could not penetrate the gel. RGD-peptides did not further improve any effect observed for PIC. The absence of adverse effects, ease of application, and the possibilities for bio-functionalization make the biomimetic PIC hydrogels suitable for development into wound dressings., (Copyright © 2018 Elsevier Ltd. All rights reserved.)