Immunomodulatory injectable microporous hydrogel scaffolds for the promotion of dermal healing in chronic wounds

• Applicant: Dr. Lucas Schirmer
• Subject Area: Dermatology ; Biomaterials
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387673810

According to the World Health Organization, each year between five to seven million chronic and complex wounds occur in North America alone. The treatment of these persistent dermal injuries remains a major issue in modern medicine as no therapy addressing the cause is yet available. While the inflammatory process is an essential step in physiological wound healing, chronic wounds remain in a constant self-sustaining state of inflammation. In these pathogenic wound environments, the ratio of inflammatory and anti-inflammatory cytokines is highly biased to the pro-inflammatory side, thus causing decreased cell proliferation, reduced matrix deposition and eventually delayed wound closure. Advanced wound care materials based on naturally occurring biopolymers such as hyaluronic acid, might offer a novel approach to support the healing process: as such biomaterials that mimic extracellular matrices (ECM) and thereby enable control over cell fate decisions through exogenous signals can be utilized to resolve the underlying pathophysiology of chronic wounds. We, therefore, propose an interdisciplinary research approach to employ microporous annealed particles (MAP) hydrogels based on hyaluronic acid in combination with the sustained delivery of TSG-6 as an immunomodulatory mediator for the control of inflammation in chronic wounds. The microporous annealed particle hydrogels, developed by Prof. Tatiana Segura’s lab, are based on preformed microgel beads that are crosslinked in situ. They combine a number of characteristics making them highly suitable for the application in dermal wound healing: due the in situ crosslinking, they can be formed in tight contact with the tissue to mechanically support the dermal tissue. They provide a physiological environment for the proliferation of new tissue through their high water content. Lastly, through their unique assembly strategy from preformed microgels and the resulting porosity, they allow fast cell invasion and sustained degradation of the material. TSG-6 (Tumor necrosis factor-inducible gene 6 protein), an immunomodulatory mediator secreted by mesenchymal stem cells during the wound repair, presents an interesting tool for the provision of an anti-inflammatory and pro-regenerative wound environment.The proposed project aims to explore these applications and further extend the MAP hydrogels through the incorporation of the glycosaminoglycan hyaluronic acid with anti-inflammatory and pro-regenerative properties and functionalization with TSG-6, a hyaluronic acid-binding protein with additional anti-inflammatory effects. The insights gained from this research project might further the future development of novel wound dressings designed to accelerate the repair processes in patients suffering from chronic wounds.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Tatiana Segura, Ph.D.