Team:CCU Taiwan/Implementation
Team:CCU Taiwan/Implementation
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Overview
In response to the increased threat imposed by antimicrobial resistance (AMR), when microbes no longer respond to medicines [1], our team came up with a solution of using antimicrobial agents–Antimicrobial peptides (AMPs) and AMP linked with a Trans-Activator of Transcription (TAT-AMP)–which are short-chain peptides that will not easily generate drug resistance in bacteria. Since wounds are one of the most common locations of bacterial infection, we came up with an antimicrobial dressing–AgenT Dressing to tackle such problems. To implement our work beyond the laboratory, we focused on AgenT Dressing’s target user, innovative design, and safety. To bring impact beyond the iGEM competition, we indicated the challenge and future work our team encountered during the competition period, as a cornerstone for future product optimization or just to spark more creative ideas.
Target Users
AMPs alone can tackle a wide spectrum of bacteria, both Gram-positive and Gram-negative, including S. aureus; E. coli; and P. aeruginosa [2]. Bacteria hiding inside cells are harder to cope with TAT, which is derived from the transcription protein TAT in HIV-1, can act as a Trojan horse carrying cargoes into cells [3]. When linked with AMP (TAT-AMP), it can penetrate the cell membrane to kill intracellular bacteria, achieving both intra- and extracellular sterilization. Our target users are those whose wounds are more likely to develop or already suffer from bacterial infections, which can be divided into two main groups:
Innovative Design
To meet different demands in wound care simultaneously, we designed a composite dressing that combines three different functional layers as described below:
Polyurethane film is widely used in wound care since it can block external contamination and easily adhere the dressing to wounds. While adhering to the skin, it is non-toxic and breathable. Therefore, we use it as our outer layer to prevent further infection and to apply the dressing conveniently.
In wound treatment, it is not only necessary to prevent outer microbial infection but also to deal with the continuous secretion of wound exudate. We selected alginate and chitosan as the ingredients of the middle layer due to their high absorbability and non-toxicity properties. At the same time, it can provide an appropriate environment for healing by absorbing excessive secretions from the wound.
The inner layer is mainly composed of collagen, combined with our antimicrobial agents to sterilize the wound. Collagen is widely used in skin tissue engineering since it can stimulate the deposition of collagen fiber and granulation tissue in the wound bed. Antimicrobial agents in the collagen layer can achieve both intra- and extracellular sterilization. Therefore, this contact layer could promote wound healing and has anti-infective properties at the same time.
For more AgenT Dressing design details, click here.
Safety
Our product, AgenT Dressing, is a novel biocompatible antimicrobial dressing. There are two aspects to user safety, the dressing itself and antimicrobial agent. Each layer of the dressing in AgenT is harmless to the human body. The outer layer, polyurethane, is a common material applied in medical treatment since it is non-toxic to human skin. As for middle and inner layers, alginate, chitosan, and collagen are also non-toxic and biodegradable materials, which will not have a negative impact on the environment.
Regarding the antimicrobial agents, the AMPs released in the environment may sterilize the nearby microbes, just as other antibiotics. However, because the AMPs are sensitive to the environmental proteases, temperature changes, or pH changes, we believe that the activity of AMPs will not last too long. Therefore, they won’t significantly cause stress to the environment. The concentration of the antimicrobial peptides and
TAT48-57 linked with DPK-060 is below the concentration causing cytotoxicity. As a result, our peptides will not harm the cells. Furthermore, the concentration of TAT48-57 linked with DPK-060 entering the cells will be below 5 μM. At this concentration, the peptides will not escape from the endosome [4]. DPK-060 cleaved by cathepsin S can’t escape from phagolysosomes either. To sum up, the peptides won’t encounter other organelles and damage them.
Challenge & Future Work
Aiming to implement our idea in the existing competitive wound dressing market, the challenges AgenT Dressing faced included:
1. The high cost of the raw materials (collagen layer) might challenge our vision of providing affordable wound dressing to the market.
2. Highly competitive wound dressing market.
3. We only focused on limited wound types at the current stage.
4. We only focus on one format of the product-wound dressing.
Our solutions to these challenges will require future work:
1. The ionic crosslinking between alginate and chitosan of the middle layer may affect AMPs, which are positively charged. Thus we selected collagen as the dressing’s base layer as the platform for AMPs because we thought that a protein coating layer could decrease the ionic influence from the middle layer. In the future, we hope to test substitute materials such as gelatin to obtain similar effects but at a lower cost.
2. Seeking the best market fit, we attained a preliminary understanding of the wound dressing market (click here for more information) for future execution.
3. Since different wound types require specific wound treatments, we will design exclusive dressings combining our antimicrobial agents in the future, such as changing the size and shape to apply on specific wounds. In the future, we will also try other materials for preparation to improve the function of our dressings and achieve better treatment efficiency at lower costs.
4. In the future we will be working on product diversification that utilizes our antimicrobial agents.
References:
1. World Health Organization (2020). Antimicrobial Resistance.
2. Patrulea, V., Borchard, G., & Jordan, O. (2020). An Update on Antimicrobial Peptides (AMPs) and Their Delivery Strategies for Wound Infections. Pharmaceutics, 12(9), 840.
3. Madani, F., Lindberg, S., Langel, U., Futaki, S., & Gräslund, A. (2011). Mechanisms of cellular uptake of cell-penetrating peptides. Journal of biophysics (Hindawi Publishing Corporation : Online), 2011, 414729.
4. Duchardt, F., Fotin-Mleczek, M., Schwarz, H., Fischer, R., & Brock, R. (2007). A comprehensive model for the cellular uptake of cationic cell-penetrating peptides. Traffic (Copenhagen, Denmark), 8(7), 848–866.
