Periodic Reporting for period 1 - SYNMAT FOR ORGANOIDS (High-throughput and reproducible development of intestinal organoids by microfluidics encapsulation in synthetic niches for intestinal bowel disease research)
Berichtszeitraum: 2022-07-01 bis 2024-06-30
Inflammatory bowel disease (IBD), which comprises Crohn’s disease and ulcerative colitis, represents a significant and growing health burden worldwide. Current treatments for IBD primarily focus on managing symptoms and inflammation but often fail to address underlying tissue damage or support long-term healing. As a result, many patients experience recurrent exacerbation of symptoms and complications, reducing their quality of life. Furthermore, conventional therapies can lead to significant side effects and, in some cases, become less effective over time. The lack of regenerative treatment options highlights a crucial gap in IBD management, underscoring the need for innovative therapeutic strategies that not only control inflammation but also promote tissue repair and regeneration. IBD affects millions globally, with increasing incidence and prevalence. This chronic condition places a heavy burden on healthcare systems due to frequent hospitalizations, expensive treatments, and the need for long-term care. Beyond its healthcare impact, IBD affects the daily lives of patients, often leading to reduced work productivity and social limitations. Developing regenerative medicine approaches for IBD would not only alleviate patient suffering and improve quality of life but also reduce healthcare costs associated with chronic care and repeated interventions.
This project aims to develop an innovative regenerative approach for IBD treatment through the encapsulation of intestinal spheroids in synthetic microgels. Specifically, the objectives include:
• Engineering of Synthetic Microgels: Develop a microgel platform optimized for the encapsulation and survival of intestinal spheroids derived from induced pluripotent stem cells. The microgels will be designed to provide a supportive environment that mimics the natural extracellular matrix and promotes the growth and function of the spheroids.
• Intestinal Spheroid Encapsulation and Functionality: Assess the ability of encapsulated intestinal spheroids to restore epithelial integrity, reduce inflammation, and secrete protective factors within an inflammatory environment. The spheroids will be tested for their potential to promote tissue regeneration in vitro.
This project aims to develop an innovative regenerative approach for IBD treatment through the encapsulation of intestinal spheroids in synthetic microgels. Specifically, the objectives include:
• Engineering of Synthetic Microgels: Develop a microgel platform optimized for the encapsulation and survival of intestinal spheroids derived from induced pluripotent stem cells. The microgels will be designed to provide a supportive environment that mimics the natural extracellular matrix and promotes the growth and function of the spheroids.
• Intestinal Spheroid Encapsulation and Functionality: Assess the ability of encapsulated intestinal spheroids to restore epithelial integrity, reduce inflammation, and secrete protective factors within an inflammatory environment. The spheroids will be tested for their potential to promote tissue regeneration in vitro.
In the first stage of the project, I successfully developed an ultrafast and facile technique to fabricate degradable synthetic microgels for cell encapsulation. These microgels were fabricated using microfluidic devices, enabling precise control over their size and structure. By applying ultraviolet (UV) light, I was able to crosslink the polymeric matrix in a controlled manner, leading to the creation of microgels with tunable degradation properties. This degradation is facilitated by the incorporation of a protease-sensitive crosslinker into the polymeric matrix, allowing for a controlled degradation of the microgel in response to specific enzymatic triggers. Human mesenchymal stem cells (hMSCs) were chosen as the proof of concept for cell encapsulation within these microgels and they demonstrated excellent cell viability and functionality after encapsulation, remaining viable over extended culture periods. These results support the potential of these microgels for use in various regenerative medicine applications.
The next phase of the project will focus on using these microgels to encapsulate intestinal spheroids, which will be derived from induced pluripotent stem cells. This step is critical for exploring the potential of these microgels as cell carriers in the context of regenerative medicine, particularly for treating IBD. The ability to encapsulate complex multicellular structures like intestinal spheroids represents a significant advancement in the development of in vitro models for disease modeling and therapy.
The next phase of the project will focus on using these microgels to encapsulate intestinal spheroids, which will be derived from induced pluripotent stem cells. This step is critical for exploring the potential of these microgels as cell carriers in the context of regenerative medicine, particularly for treating IBD. The ability to encapsulate complex multicellular structures like intestinal spheroids represents a significant advancement in the development of in vitro models for disease modeling and therapy.
This project aims to significantly advance current cell encapsulation techniques and regenerative medicine by developing degradable synthetic microgels specifically designed for encapsulating stem-cell-derived intestinal spheroids. To date, no microgel-based approach has been described that effectively encapsulates these spheroids, which can serve as cell carriers with potential applications in regenerative medicine. By the end of the project, we intend to deliver a scalable, validated microgel platform that ensures long-term viability and functionality of encapsulated cells, with a particular focus on treating IBD. The incorporation of protease-sensitive crosslinkers will allow for precise control over degradation, creating a dynamic, tissue-like environment that better supports cell behavior and tissue regeneration. One key advantage of using synthetic polymers, such as polyethylene glycol (PEG)-based microgels, over natural polymers or Matrigel is the ability to precisely tailor the material properties, including degradation rates, stiffness, and bioactivity, which can be optimized for specific therapeutic applications. In contrast, natural polymers often have batch-to-batch variability, limited control over their mechanical properties, and can introduce unwanted immunogenic responses. Additionally, synthetic polymers can be easily modified to include specific functional groups, enhancing cell-matrix interactions in a more controlled and predictable manner. If successful, this project could have a significant socio-economic impact, offering a potential alternative to chronic medication and frequent clinical treatments for IBD, thereby reducing healthcare costs and improving quality of life of IBD patients. Beyond IBD, the versatile nature of these microgels could have broader applications in treating other chronic diseases, establishing a new class of adaptable biomaterials for regenerative therapies.