PORTFOLIO

Hard-to-heal wounds represent a major medical problem for individual patients and due to the high associated healthcare costs also for society at large. Notably, most patients recovering from wounds develop scars after wound closure. Scars do not only have an aesthetic impact, but depending on their location they can greatly compromise the mobility of a patient if e.g. extended over a joint. Current wound treatment approaches focus mainly on the protection of the wound from a healing-unfriendly environment, mostly neglecting the prevention of scar formation. A scaffold that not only promotes wound healing but at the same time also prevents scar tissue formation could thus have a tremendous impact on current wound treatment procedures.

The aim of the current project is to develop a synthetic and bioactive 3D scaffold based on the FDA-approved material P4HB, addressing two key aspects of wound healing simultaneously, i.e. stimulating correct skin regeneration and prevention of scar formation. P4HB-scaffolds with defined micro- and macrostructure to steer the response of skin cells and tailored properties for drug- release and scaffold degradation rate to parallel tissue regeneration will be developed. In order to evaluate the feasibility of the envisioned approach and to optimise the scaffold properties, the degradation velocity and drug release pattern will be studied; the ability to support cell/tissue ingrowth into the scaffold and bioactivity of the foam scaffolds to prevent the formation of contractile skin cells, key players in scarring, will be investigated. Ultimately, the functionality of the foam to support tissue regeneration and to prevent scar formation in vivo will be verified in excisional wounds in rats.

The vision of this project is to develop a novel synthetic and bioactive scaffold that not only promotes wound healing but also prevents scar tissue formation; a medical need that, despite affecting millions of patients each year, has not been addressed sufficiently to date. By using the FDA approved P4HB as scaffold material, faster translation into clinics can be expected. In case of success an impulse towards a complete new class of wound treatment products could be given that may not only be used for hard-to-heal wounds, but also for acute wounds or wounds resulting from planned surgeries.

In the course of this project, we have successfully developed biodegradable 3D polymer (Poly-4-hydroxybutyrate (P4HB)) scaffolds with tunable pore sizes in the range of interest and high interconnectivity. Prepared P4HB materials allowed attachment and invasion of skin cells (i.e. fibroblasts) and were found to be cytocompatible. Two natural drugs that counteract the formation of contractile skin cells have been identified and concentration ranges where these drugs are active but not cytotoxic could be defined. Interestingly, the two drugs showed synergistic effects, which suggests that they affect skin cells via different mechanisms. P4HB foams were successfully loaded with the most promising drug candidate. We observed a homogenous distribution of the drug inside the polymer foam and a continuous longterm release. Furthermore, in in vitro studies we demonstrated that the biofunctionalized foams inhibited myofibroblast formation and had an antiinflammatory effect on macrophages. Finally, as an ultimate proof of concept, the excellent bioactivity of our newly developed scaffolds could be demonstrated with improved wound healing in a small animal model.

In preperation

Wundschaum aus Kurkuma, SRF, Sendung «Pulsmix», 26.8.2019
Kurkuma soll Wunden heilen, Pro7, Sendung «Galileo», 20.8.2019
Kurkuma-Schaum hilft der Wundheilung, scinexx, 19.8.2019
Schaumstoff mit Kurkuma soll die Wundheilung verbessern, Pharmapro.ch, 15.8.2019
Coverage in numerous other media