Overview

Adhesives are present in many aspects of modern life, from household repairs to industrial large-scale applications. However, these synthetic adhesives often raise serious environmental and health concerns due to their non-biodegradable properties and toxicity [1]. Simultaneously, the global demand for adhesive products continues to rise, with the industry expected to grow by approximately one billion USD from 2023 to 2024 and annual global consumption reaching 24.7 million metric tonnes [2][3]. Not only that, but the medical industry heavily relies on adhesives, with devices such as ECG sensor patches, insulin pumps, and glucose sensors [4]. Unfortunately, those patches peel off prematurely, and the adhesives used in these applications can lead to allergic reactions and dermatitis. These factors can cause severe problems for patients, especially those with chronic conditions like diabetes [5].

Target Users and Problem Statement

Our project, Synhesion, addresses a pressing need in diabetes care by creating bio-based, hypoallergenic adhesives suitable for medical patches. This innovation is crucial for the 537 million people worldwide living with diabetes, many of whom use insulin pumps and continuous glucose monitors (CGMs) (Fig. 1) [6]. Currently, these devices depend on synthetic adhesives, which often cause skin irritations, allergic reactions, or premature detachment [4][7]. Losing these devices can be very expensive and pose serious health risks. As insulin pumps and glucose monitors cost up to 5,000 USD, it is vital to ensure the patches stay in place without causing life-threatening complications.

Through surveys and interviews with diabetes patients, the Diabetes Association of Lithuania, and healthcare specialists, we identified that these adhesive-related issues significantly impact quality of life. Therefore, developing an adhesive solution that mitigates these problems is critical to improving patient care and safety.

Proposed Solution

Synhesion offers a revolutionary solution by leveraging genetically engineered Escherichia colito produce bio-based adhesives derived from the polysaccharides, called holdfast, from Caulobacter crescentus. Bacterial adhesives produced by C. crescentus are among the strongest known biological adhesives and exhibit biocompatibility, making them ideal for medical applications [8][9]. By transferring the holdfast-producing system into E. coli, we can take advantage of its well-established culturing techniques to achieve scalable, cheaper, 7 times faster, controllable, and efficient production [10][11]. This allows us to create a natural adhesive that is not only stronger than traditional superglue but also reduces the risk of skin irritation and allergic reactions, providing a skin-friendly alternative for medical patches [9].

Implementation and Use Case

Synhesion offers a sustainable, biodegradable alternative to synthetic adhesives and helps people with diabetes. This new adhesive, developed through synthetic biology tools, targets individuals who rely on insulin pumps and glucose sensors. Through our innovative approach, we aim to significantly enhance the daily lives of diabetes patients worldwide, providing them with a safer and more reliable adhesive solution.

User-friendly Industrial Production of Adhesives

Monitoring and ensuring optimal bacterial growth conditions can often be time-consuming due to the long periods required for bacteria to grow and replicate. We used the Scrum framework to implement the remote monitoring system (see Software) for our bioreactor (see Hardware), delivering features incrementally and refining the product through user feedback. This allowed us to address the real-time needs of our wet lab and future scalability, which directly influenced the system’s functionality.

The development started with defining the Minimum Viable Product (MVP) and progressed through several iterations:

• MVP1: A website capable of storing bioreactor temperature and pH readings.
• MVP2: Remote control of the bioreactor’s mixing speed and temperature.
• MVP3: Turbidity monitoring to track bacterial growth.
• MVP4: An alert system sending notifications when readings exceed preset thresholds.
• MVP5: Glucose concentration monitoring and an automated feeding mechanism for bacterial growth optimization.

This iterative process ensured that the bioreactor system met the lab’s needs while automating data collection and reducing the time required for supervision.

Architecture

The architecture of the bioreactor monitoring system included several key components (Fig. 2):

1. PostgreSQL Database: Stored all bioreactor data and control settings.
2. Python Flask Server: Acted as the backend, providing data handling and automated processes.
3. Arduino Client: Collected real-time bioreactor measurements and sent them to the server.
4. React Web Client: Allowed users to monitor and control the bioreactor remotely.

By integrating these components, we created a fully automated and remotely accessible system for bioreactor management, ensuring scalability for large-scale adhesive production.

Future Prospects and Industrial Applications

In addition to benefiting diabetes patients, our bio-based adhesives present exciting opportunities for broader applications in medical devices and industrial manufacturing. The polysaccharide-based holdfast produced by C. crescentus can be adapted for various industries, from eco-friendly construction materials to medical equipment, contributing to a more sustainable and health-conscious world. Our technology also positions Synhesion as a key player in the shift towards greener alternatives in the adhesive industry.

Challenges and Considerations

Synhesion still needs to overcome some challenges. For example, our polysaccharide is not easily purifiable at the moment, necessitating more research and experiments to produce actual adhesives. Furthermore, we must test the produced polysaccharide on its adhesive properties, degradation, and biocompatibility. In this way, the adhesive properties will be improved to meet the needs of various medical and industrial applications.

Intellectual Property and Startup Development

Throughout our iGEM journey, we have consulted with experts to turn Synhesion into a viable startup (see Entrepreneurship). With guidance from Dr. Eglė Radzevičienė, a patent attorney specializing in intellectual property, we explored our product’s patentability. Once we received feedback on our foundational results, verifying and legitimizing our work, we started the process of obtaining a patent. Financial challenges are being addressed with the help of Violeta Sutkienė from METIDA, who introduced us to reimbursement options to cover part of the patent fees. We are preparing to enter the Baltic Sandbox Ventures pre-accelerator program for financial support, moving closer to securing our intellectual property and launching our startup.

Adaptability of Polysaccharide Synthesis Beyond the Glue

Medical research constantly looks for new ways to deliver drugs and gene editing systems without harming healthy cells. These drugs require high specificity without alerting the immune system. Liposomes are spherical-shaped vesicles that comprise phospholipid bilayers and resemble the structure of cell membranes. They are used as nanocarriers for their unique biocompatibility properties, biodegradability, and low immunogenicity [12]. Human cells use uniquely recognizable glycolipids as markers for cell-to-cell communication and immunogenic responses. Therefore, glycolabeled membranes are the perfect target for specialized drug delivery. [13]. This is where our characterized system comes into play - glycosyltransferases of the holdfast synthesis system could be involved in polysaccharide assembly on lipid carriers (Fig. 3). This results in creating a custom liposome labeling strategy and provides a strong foundation for tunable glycolipid assembly.