Design of Thiomers for In-Situ 3D Bioprining

In-situ 3D bioprinting is revolutionizing the field of tissue engineering, offering a game- changing approach for the repair and regeneration of damaged tissuesdirectly at the site of injury. By enabling the on-demand fabrication of complex tissue structures, this technology holds immense promise for personalized, real-time medical interventions. However, the journey from lab to clinic presents critical challenges, particularly when it comes to ensuring tissue adhesion, biocompatibility, and structural integrity under real-world conditions. At the heart of this innovation lies the development of bioinksspecialized materials that support cell viability and tissue development. Among them, hydrogels stand out for their unique ability to mimic the extracellular matrix (ECM). In this groundbreaking project, researchers focus on a highly promising class of hydrogels based on thiolated polymers, known as thiomers. These materials form disulfide bonds with tissue surfaces, offering strong adhesive potential. Yet, one major hurdle remains: achieving robust and lasting adhesion in tissues that are constantly in motionsuch as the heart, esophagus, gastrointestinal mucosa, and lungs. Addressing this unmet need, the project sets out to develop next-generation thiolated polysaccharide-based bioinks engineered for high-performance adhesion in dynamic biological environments. Led by Professor Andreas Bernkop-Schnürch, the research team is pursuing a dual strategy. First, they are designing interpenetrating polymer networks to reinforce tissue anchoring. Simultaneously, they are exploring targeted tissue pretreatments that optimize the adhesive interaction between the bioink and the biological substrate. In addition, the project investigates how crosslinking mechanismsparticularly the degree and timing of crosslinkingaffect the mechanical strength, elasticity, and overall performance of the printed constructs. A wide range of thiolated polysaccharides and crosslinkers are synthesized, systematically analyzed, and evaluated in both in vitro and in vivo models. This is the first study dedicated to enhancing the adhesive properties of bioinks for in-situ bioprinting on moving tissues, marking a significant milestone in the field. The project includes: (i) The design of novel thiomers and crosslinkers, (ii) The discovery of effective tissue pretreatment strategies, and (iii) The development of new test methodologies for dynamic adhesion performance. With its innovative approach, this research aims to accelerate the clinical translation of in-situ 3D bioprinting and pave the way for next-generation, patient-specific solutions in tissue repair and regenerationeven in the most challenging and dynamic environments.