Perspectives

We realized early on that there are many interesting applications for our chosen sub elements, and as we got to talk with different experts, we saw even more opportunities. On this page we have highlighted some of the most interesting applications, to give you a broader perspective of the true potential of each sub element. We have also included some of the high school students' ideas from the workshops. So take a look and be inspired to how Bacto-Aid’s sub elements can be integrated in your future.

Bacteriocins

The promising MIC results of the bacteriocins gives us the opportunity to use them as a supplement to traditional antibiotics, thus facing the evolution of antimicrobial resistance (AMR). Here is some of the ideas for their future applications.

Combination of traditional antibiotics with bacteriocins (Top)

The bacteriocins could serve as a supplement to traditional antibiotics, since our purified bacteriocins are capable of inhibiting the growth of Methicillin Resistant S. aureus strains. It could also be hypothesized that a combination of traditional antibiotics with bacteriocins could elicit a synergistic effect towards resistant bacterial strains. This leaves us with the opportunity to shift the balance of resistance. This could prevent the evolution of antimicrobial resistance against traditional antibiotics Dan, Y., et al. (2012). "Bacteriocins Produced by Lactic Acid Bacteria a Review Article." APCBEE Procedia 2: 50-56..

Combination with pulsed electric fields (Top)

A combination of bacteriocins and technologies, such as pulsed electric fields, enables us to disrupt the cellular membrane for penetration of the cell and have been suggested to be highly effective Dan, Y., et al. (2012). "Bacteriocins Produced by Lactic Acid Bacteria a Review Article." APCBEE Procedia 2: 50-56.. This method could be a way for us to give the hybrid bacteriocin Laterosporulin-ThuricinS access to cross the cell membrane of P. aeruginosa. This technology can also be a way for us to optimize the effectiveness of the bacteriocins generally.

Bacteriocins as probiotics (Top)

Probiotics are living microorganisms that when consumed in modest amounts, it confer to health benefits for the host. Studies have demonstrated the impact of bacteriocin-producing strains’ ability to compete within complex microbial communities and thereby influence the health of the host. It was shown that bacteriocins are able to directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota. This can have an influence on the host immune system Dobson, A., et al. (2012). "Bacteriocins Bacteriocin production: a probiotic trait?" Appl Environ Microbiol, 78, 1-6.. However, when using bacteriocins as probiotics it is important to make a thorough evaluation of the ethical aspects of it, as well as a risk assessment.

It is suggested that probiotics producing bacteriocins could lead to positive probiotic functionality in a number of ways:

• Bacteriocins could function as colonizing peptides, facilitating the introduction and dominance of a producer into an already occupied niche, thereby facilitating the competition of probiotic bacteria with the unfavourable resident bacteria.
• Bacteriocins could act as antimicrobial peptides that directly inhibits competing strains or pathogens.
• Bacteriocins could function as signalling peptides that either 1) signals other bacteria through quorum sensing and bacterial cross talk within microbial communities, or 2) through signalling cells of the host’s immune system Dobson, A., et al. (2012). "Bacteriocins Bacteriocin production: a probiotic trait?" Appl Environ Microbiol, 78, 1-6..

Ointment against MRSA (Top)

Purified or partially purified bacteriocins hold great promise in treating an unhealthy bacterial flora by targeting pathogenic bacteria. They may be employed as pharmabiotics or novel alternatives to existing antibiotics. Promising results have been shown in fighting MRSA with purified bacteriocins Dobson, A., et al. (2012). "Bacteriocins Bacteriocin production: a probiotic trait?" Appl Environ Microbiol, 78, 1-6.. Hans Jørn Kolmos suggested that we could use pure bacteriocins in a ointment, which can be applied at the nostrils to avoid MRSA that typically niches here. Applying the bacteriocins at the nose will make their effect most effective on carriers.

Bacteriocins for medical equipment (Top)

It has been proven that surgical suture coating with antimicrobial peptides incorporated is more effective than the Vicryl Plus Antimicrobial Suture against S. aureus in time-kill experiments Li, Y., et al. (2012). "New bactericidal surgical suture coating" Langmuir : the ACS journal of surfaces and colloids., 28(33), pp. 12134–9.. There lies therefore great potential in using bacteriocins for medical equipment.

Spider Silk

Recombinant spider silk can be used for many purposes. Today’s goal for wound treatment is a patch that can provide protection, care and minimize the amount of pain, the patient might experience. During our project with creating Bacto-Aid, we found out that the silk’s potential is great. Here is some of the ideas for its future application.

Creation of skin cell culture (Top)

It has been a goal for many years to get a material that is as close to human skin as possible, because skin grafting from other parts of the body or donors is often limited. There has also been tentatives of combining it with keratinocytes and fibroblasts to create a skin cell culturing. It was also shown that spider silk could guide the proliferation of the cells in the proper directions (staying in the frame) Wendt, H., et al. (2011). "Artificial skin--culturing of different skin cell lines for generating an artificial skin substitute on cross-weaved spider silk fibres." PLoS ONE, 6(7), pp. e21833..

Antimicrobial gauze (Top)

As an alternative to our Bacto-Aid, our hybrid silk could be used as an antimicrobial gauze. The gauze could then be used for larger wounds and for wounds producing a lot of fluids. The fluids was a problem that Laura Jakobsen made us aware of, and the gauze could be a way of solving this. An addition to this idea would be to dip the gauze into the analgesic Ibumetin.

Soft implants (Top)

Soft implants have been subject of interest the last couple of years. Here it has been suggested that spider silk could be braided in a structure and grafted to the bone Li, G., et al. (2015). "Silk-based biomaterials in biomedical textiles and fiber-based implants." Adv Healthc Mater, 4, 1134-51.. This would allow quicker healing of the bone and ensure the creation of proper bone structure.

Nerve scaffolds made of spider silk have likewise shown great potential. Usually bigger motor neurons will not regenerate if degraded or cut. Silk as nerves, could lead to the gain of motoric activity in extremities that could otherwise not be regained after major accidents Li, G., et al. (2015). "Silk-based biomaterials in biomedical textiles and fiber-based implants." Adv Healthc Mater, 4, 1134-51..

Some types of silk have great mechanical strengths and they can therefore be used as an artificial ligament or tendon. The combination of silk with stem cells could allow cells to proliferate and differentiate into the proper type of cells. This could potentially make tendons and ligaments heal, a thing that does not occur naturally Li, G., et al. (2015). "Silk-based biomaterials in biomedical textiles and fiber-based implants." Adv Healthc Mater, 4, 1134-51..

Textiles made from silk (Top)

Silk could be used as a textile for surgeons or for patients with skin disorders. The spider silk is compatible with today’s sterilization process, making it possible to use silk for different forms of medical interventions. Already existing silk products have shown good results towards reducing the reaction of the disease in question Li, G., et al. (2015). "Silk-based biomaterials in biomedical textiles and fiber-based implants." Adv Healthc Mater, 4, 1134-51..

PHB

Previous iGEM teams (Tokyo Tech 2012 and Imperial College team 2013) have retrieved promising results in improving the production of PHB. With our introduction of a secretion system, the PHB production might end up being a financially beneficial solution to the current plastic consumption. Here is some of the ideas for PHB’s future application.

Implants and coating for guided bone regeneration (Top)

PHB is biocompatible and biodegradable. This makes it well suited for application inside the human body due to the hydrolysis of the polymer that produces a ketone body, commonly found in blood Rodriguez-Contreras, A., et al. (2016). "Modification of titanium surfaces by adding antibiotic-loaded PHB spheres and PEG for biomedical applications." J Mater Sci Mater Med, 27, 124.. These properties gives PHB the capability to become an implant that could be broken down slowly under the healing process of the bone. The slowly degradation of the plastic makes it useful to guide the bone regeneration. Using PHB as an implant could allow us to 3D print the structure of a joint, and by that fulfill the medical field’s wish to create treatments adapted to each patient.

This type of plastic is also suitable for load-bearing orthopedic implants, as the moduli of elasticity, tensile strength and strain properties of PHB are similar to bone material Meischel, M., et al. (2016). "Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications." J Mech Behav Biomed Mater, 53, 104-18.. PHB’s strong alkaline ester linkages makes its surface more hydrophilic. This gives human osteoblasts the opportunity to proliferate and inhibit the growth of S. aureus on the surface of the implant Karahaliloglu, Z., et al. (2015). "Antibacterial Nanostructured Polyhydroxybutyrate Membranes for Guided Bone Regeneration" J Biomed Nanotechnol, 11, 2253-63. Karahaliloglu, Z., et al. (2015). "Antibacterial Nanostructured Polyhydroxybutyrate Membranes for Guided Bone Regeneration" Hua Xi Kou Qiang Yi Xue Za Zhi, 18, 215-8.. PHB will therefore be able to create a secluded space, where it is possible to avoid infection and the formation of fibrous connective tissue.

Coating of implants in combination with antimicrobial compounds (Top)

Today’s implants could also be improved by a bactericidal coating of PHB. Implants used today are often made of titanium, which have no bactericidal effect. When inserted into the body, a bacterial contamination could create a biofilm, which could resolve in an infection and a necessity to remove the implant again Connaughton, A., et al. (2014). "Biofilm disrupting technology for orthopedic Implants: What’s on the horizon?" Frontiers in Medicine, 22.. PHB could be loaded on the surface of the implant as spherical micro- or nano particles loaded with antibiotics or bacteriocins, as suggested by Morten Østergaard Andersen. The bacteriocins will be released continuously and thereby prevent infections and biofilms.

Intracellular drug delivery (Top)

One of today’s issues among drug delivery systems in the human body, is when a drug has to be transported intracellularly. PHB nanoparticles can cross the plasmalemma, thereby solving one of our treatment limitations Kapoor, S., et al. (2016). " Intracellular delivery of peptide cargos using polyhydroxybutyrate based biodegradable nanoparticles: Studies on antitumor efficacy of BCL-2 converting peptide, NuBCP-9." FInt J Pharm, 511, 876-89..

There is, likewise, an increasing wish to create a personalized treatment to each patient. To avoid side effects and fulfill today’s wish, an in vivo drug delivery gel based on PHB could provide a non-invasive, local and steady release of medicine. In the example of cancer, the degradability of PHB is taken in advantage by incorporating the chemotherapeutic into the gel. As the gel is degraded, the medicine is released. Adding or changing components of the gel, changes the rate of which the medicine is released, thus allowing customization Wu, L. Y., et al. (2016). " PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors." Adv Healthc Mater..

Future market for PHB (Top)

Plastic is a big part of many daily routines. Biodegradable plastic, produced by E.coli, has a huge potential, because it can possibly replace conventional plastic. The main thing that withholds this from happening, is the price. PHB is today far too expensive compared to the traditional production. Nevertheless further improvement in mass production of biodegradable plastic offers a wide spectrum of usage, e.g. in the agricultural and horticultural sector, for food, medicine packaging and much more " PlasticsEurope ". Hopefully, this breakthrough will happen within the next 10-20 years and thereby change the plastic market drastically. The price of one kilo Polystyrene (used commonly in today’s tableware) is between 0.50-1.29€ " Plasticker". PHB’s price is however, very high at the moment. A price around 1.5 - 2€ pr/kilo may rise the interest of PHB for future investors.

Our contact with several plastic companies gave us hope for this to happen, but they also pointed out, that it is the customers that should be convinced if they were going to implement PHB in their company.

In a not so distant future...

Ideas from high school students (Top)

We asked the students to imagine how our project would be incorporated in 50, 100 and 150 years in our everyday lives. They were especially very interested in the future prospects of bacteriocins. Some of their ideas are presented here.

50 years

• Bacto-Aid can prevent scar tissue creation
• it will be possible to buy Bacto-Aid at the local pharmacy and grocery stores. Hospitals will use it and it will be a part of people’s first aid kit
• Bacto-Aid will be in spray form
• Bacto-Aid can treat people with psoriasis

100 years

• bacteriocins could be a composite of makeup, shampoos and creams to prevent infections
• bacteriocins could be applied on door handles to prevent bacteria to spread
• disinfection gels will contain bacteriocins. Hans Jørn Kolmos also told us that resistance towards disinfection gels has become more common. We are therefore obliged to invent a new alternative
• Bacto-Aid can now be bought as a cream and in a tablet form. The tablet will be able to cure internal infections
• the bacteriocins will be incorporated in bedclothes
• apply bacteriocins in chewing gum
• Bacto-Aid as a special bandage for people with amputated bodies

150 years

• here we might go back to the antibiotics we know today
• chip in the body which sends out bacteriocins when needed, e.g. for old people
• bacteriocins will make our food last longer
• bacteriocins will be in medical suits and operation gloves

Roger, over and out (Top)

These are just a few examples of the possible applications, that our project contains. We have mainly focused on the medical sector, but other applications can be assumed as well. It is just the beginning and as Thomas Edison said: “There’s a way to do it better - find it”. The foundation for our idea has now been made, but we will continue to improve our idea and hopefully one day we will end up with a sustainable product, which we can commercialize.

We look forward to present our project in Boston, and hear about all the other iGEM projects.

Thank you for reading our interactive lab book, we hope you enjoyed the tour!

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