No abstract

Herein, we report on the precise design of a modular fusion protein amenable to the construction of nanocapsules by nanoprecipitation. The central squid suckerin-derived peptide block provides structural stability, whereas both termini from spider silk fibroins make the protein highly soluble at physiological pH, a critical requirement for the nanoprecipitation process. With this design, nanocapsules consisting of fusion protein shells and oily cores with sizes in the range of 190−250 nm are built in a straightforward manner.

Chronic wounds are non‐healing wounds characterized by a prolonged inflammation phase. Excessive inflammation leads to elevated protease levels and consequently to a decrease in growth factors at wound sites. Stem cell secretome therapy has been identified as a treatment strategy to modulate the microenvironment of chronic wounds via supplementation with anti‐inflammatory/growth factors. However, there is a need to develop better secretome delivery systems that are able to encapsulate the secretome without denaturation, in a sustained manner, and that are fully biocompatible. To address this gap, a recombinant squid suckerin‐spider silk fusion protein is developed with cell‐adhesion motifs capable of thermal gelation at physiological temperatures to form hydrogels for encapsulation and subsequent release of the stem cell secretome. Freeze–thaw treatment of the protein hydrogel results in a modified porous cryogel that maintains slow degradation and sustained secretome release. Chronic wounds of diabetic mice treated with the secretome‐laden cryogel display increased wound closure, presence of endothelial cells, granulation wound tissue thickness, and reduced inflammation with no fibrotic scar formation. Overall, these in vivo indicators of wound healing demonstrate that the fusion protein hydrogel displays remarkable potential as a delivery system for secretome‐assisted chronic wound healing.

and A. Miserez. Squid suckerin-spider silk fusion protein hydrogel for delivery of mesenchymal stem cell secretome to chronic wounds.