Team:Aalto-Helsinki/Applied Design
Applied Design
Our Applied Design page tells where we found inspiration from and how we gathered and utilized the knowledge in order to create new kind of design by using input coming from synthetic biology.
Early Research
When we started to research and design the laboratory part of our project around the antimicrobial dermcidin, we did not have any clear conclusion of the possible application and design. Fortunately, instead we had a large number of ideas. The first approach was to use dermcidin in a hospital environment, because we knew it would be active against some most common hospital bacteria. During the ideation processs, we decided to include a cellulose binding domain together with dermcidin in order to enable binding with cellulose-based materials that are widely used in hospitals. We were also pondering whether dermcidin could be used as a sterilization spray or as a coating on different surfaces or door handles, or if it could be used in diapers, cellulose-based catheters and implants.
During the process we arranged several meetings with professionals from many different fields. We went to those meetings with an open mind to be able to reflect our ideas with professionals and get tips and guidance to be able to develop the design further.
In the beginning of our project on May we had a meeting with Tarja Jalava, a researcher from Bayer. Because of a confidentiality agreement we cannot elaborate more.
First, we focused on wound care because the initial idea was to create an antimicrobial wound care product, akin to a bandage, dressing or an antimicrobial gel by using dermcidin instead of, for example, silver. We met the dermatologist Kirsi Isoherranen and the wound care nurse Ulla Väänänen from Skin and Allergy hospital of HUS. They introduced us to the versatile world of wound care products and we were able to follow wound care patient reception and saw how different products are used in action.
Ulla Väänänen showing us an antimicrobial gel, which is used in wound care.
We also visited another hospital, Jorvi, and met with the burn wound specialist Andrew Landlord there. We learned about the different techniques and products used when treating burns, but since the usage of antimicrobial agents was minimal, especially in the early stages of healing burns, we decided not to focus too much on this subject.
Changing the Topic from Wound Care to Acne
Although the field of hospital products was really promising for new solutions based on dermcidin, we were slightly unsure if that track was the correct choice for us. We wanted to execute a project that would increase the knowledge of synthetic biology and the possibilities it represents. We felt that a specialized hospital product would be a too narrow approach and would make it hard to communicate with people outside the scientific circles. After long discussions between our team members, we decided to focus on another idea we had had from the early beginning in our heads – skin care and especially acne.
What Is Acne
Acne is a result of four abnormal processes. The male hormones induce the excessive production of sebum in the hair follicles. This excess sebum causes dead skin cells to stick together resulting in a blocked hair follicle. This is called a microcomedone. Inside the clogged pore, the biofilm formation by certain strains of the skin commensal, in particular Propionibacterium acnes, causes inflammation by activating the innate immune system. Several pro-inflammatory chemical signals that are known to contribute in the comedo formation are released due to the inflammation caused by P. acnes. These chemical signals attract white blood cells to the hair follicle, resulting in a pimple. [1] [2] [3] [5]
Antibiotics are widely used in acne treatments, but many countries have reported that around 50 % of P.acnes strains are resistant to them.[2] Antimicrobial peptides, or AMPs, have been suggested as an alternative for antibiotics, which was good news for us. What encouraged us more was a study stating that acne patients had reduced expression of dermcidin on their skin, which, when fixed, we hoped would result in fewer pimples. [4] Acne is such a common problem around the world that it was easy to find information about it and stories about people struggling with acne. We still wanted to dig deeper and arranged meetings with professionals who are specialized in treating acne.
We met Antti Lauerma from Skin and Allergy hospital of HUS in order to learn more about acne and especially how acne patients are diagnosed in hospitals and what kind of medication they are using. We learned that it is not only bacterial infection causing the acne skin to produce pimples and pustules, but it can also be caused by washing the skin too much, which can easily result in drying of the skin, and the dry skin and dead skin causes more infection by blocking pores.
To get a better sense of the bigger picture, we also talked with Ida-Maria Rantala, who is a cosmetologist focused on acne patients. She told us about the treatments they are using in beauty clinics and what are the biggest trends in a beauty and skin care markets at the moment.
We got a feeling that people suffering from acne are desperately ready to commit to really heavy and sometimes painful treatments to cure acne or to make it at least a bit better. We learned about the dramatic side effects caused by some medications and about the surprisingly expensive prices of treatments and products that are commonly used against acne.
more than half of the face is involved
Meeting and talking with professionals was really important and we gained a lot of new knowledge. But most inspiring and touching were our talks with normal people who shared their stories regarding acne really openly. We interviewed 4 people about their acne. We also conducted a survey, where we collected information about people’s acne, causes, levels, backgrounds and most importantly about the products they are using to treat their acne. We wanted to know what kind of products people are willing to use and what kind of skin care routines acne patients have. We learned that people suffering acne were more willing to spend money and time on skin care in order to get their acne better. They were also more open for new products than we anticipated and willing to try different treatments and methods.
more than half of the face is involved
Acne is not only a nasty disease but it can also cause low self-esteem and mental problems. These were some of the things we talked about with Pepita Hänninen psychotherapist focused on working with young people. She thinks that the problem should not be belittled, since it can have a major impact on young people. Hänninen thinks that acne can worsen a person’s mental state if they are already feeling insecure or depressed, but the skin condition itself is rarely the main cause of mental health problems.
Design Process
After interviewing people and going through skin care products, acne products and medication already existing on the market, we had a picture in our heads of what our product should be like. Antimicrobial, natural and sustainable, purifying and exfoliating scrub that is simple and cheap to produce and easy to use. We wanted to create a natural substitute product for heavy treatments and medicines that are currently used for acne.
Porifi – Purify Your Pores from Acne Bacteria
Porifi is an everyday exfoliating scrub for cleaning your pores from acne bacteria. This refreshing and rich exfoliating formula gently removes dead skin while supporting the skin's natural dermcidin balance and helping your skin to prevent acne bacteria.
Considering our concept and product design, the end product needs to be safe to use on the human skin on an everyday basis. We are lucky in this regard, as the dermcidin peptide (DCD-1L) we worked with is already present on the human skin. The only thing that needs to be considered is whether abnormally high concentrations of the peptide risk the development of bacterial resistance to it. In that case, the body would lose its natural mechanism of defense against acne among other pathogens. One article hypothesizes, however, that it may be much less likely that resistance develops to this peptide, as the peptide is evolutionarily very recent and resistance would require big changes in the constitution of the bacterial cell wall or membrane.
Cellulose Hydrogel
Cellulose hydrogel
We wanted to use as natural materials as possible and still focus on cellulose materials. Finland is a country of wood based biomaterials and especially cellulose so it was really a matter of national pride to proceed in that direction with the application design. We decided to work with Carboxymethylcellulose (CMC) -based hydrogel because it was a really fascinating and a new material for us, but had already been proven to be non-toxic and is widely used in the food industry and as a base material in pharmaceuticals.
Carboxymethylcellulose (CMC) from CP Kelco
pH measurements for cellulose hydrogel
With CMC we got a lot of support from Aalto Bioproduct Centre and Andreas Lindberg. He gave us two CMC powders and advised us with other versatile cellulose materials.
Maisa making and experimenting with cellulose hydrogel samples
After all the research, reflection, ideation and interviews, the product design process itself was pretty simple. We made several hydrogel mixtures with different textures and densities. We experimented with those and selected the best and most promising ones and measured the viscosity.
Viscosity of the hydrogel was really important property because we wanted structure to be dense enough to be able to mix the hydrogel with exfoliation beads, but not too sticky or neither too heavy. Viscosity also greatly affects consumer perception of the product, being often mentally linked to product quality and richness. The perfect, desirable structure of the hydrogel would be gel that softens and gets less viscous as it is rubbed onto warm surfaces like skin. We conducted measurements using a Brookfield rotational viscometer with RV spindles.
Viscometer and spindles
During the viscosity measurement, we kept the temperature constant at 24 - 25 °C and measured the hydrogel viscosity at different spindle speeds (0.1 - 200 rpm). We decided to test the hydrogel samples at a broad range of speeds due to its non-newtonian behaviour which means that its viscosity decreases under shear strain (shear-thinning effect). Moreover, assuming that the cosmetic will undergo different shear stress rates while scooping out from the package, keeping still on fingers, and applying on face by rubbing, we were interested in how viscosity under these conditions would change. We neglected, however, to measure the effect of temperature.
The results of our measurements confirmed the non-newtonian behaviour of the CMC-based hydrogel. As it is shown in the graph below, when the shear stress increases the viscosity decreases for all samples. The viscosity changes by one or two orders of magnitude with applied shear stress, depending on the CMC grade and concentration. However, the change in viscosity is also completely and near instantaneously reversible, and the original viscosity is retained when the shear stress stops.
Exfoliants
When we were selecting the perfect material for the exfoliation beads, the most important point was to be environmentally friendly and to avoid all kinds of microplastics and synthetic materials. First, we were thinking about biodegradable cellulose based beads, but due the lack of time we decided to go with ground peach pits. We tested different grades of ground peach pits with different hydrogels. We were also critical of microbeads, which many cosmetic companies use as exfoliating agents in their products. Microbeads are tiny plastic particles which end up in the oceans, as they cannot be effectively filtered from the waste water with current methods. After, through plankton, they start to accumulate in fish and fish-eating birds. Cosmetics are one of the major sources for microplastics that end up in the environment. In the beginning of 2017, microplastics were already detectable from table salt. Microbeads could be replaced with an alternative that does not have such a huge impact to the environment. Currently, it is common to scrub one’s face with granulated sugar, but for commercial exfoliation products an insoluble option should be used. We thus introduced ground peach seeds as a replacement to combat the trend of microplastics! Our end product is therefore environmentally friendly, and is safe to discard in the biowaste and the sink.
Picture on left: Filters for the grinding machine
Picture on right: Anderas Lindberg helping us with the grinding machine
We used natural beads made of peach pits. We grinded them to achieve beads of different particle sizes: coarse (heavy), medium (mix) and fine. Then, we added them to hydrogel samples to get different compositions of our gel. The viscosity also impacts the sedimentation rate of the exfoliating beads suspended in the hydrogel.
Different samples of hydrogel mixed with exfoliants
After testing several different mixtures and compositions of hydrogel and exfoliants, we decided to use 3 % mixture of CMC 50 000 high molecular weight together with heavier exfoliant beads. In the proto sample stage, this felt like the best combination on the skin and also the viscosity of the hydrogel was high enough.
The final mixture
Preservatives
During the design process we contacted Andrzej Urlinski from the Urlinski company in order to receive input on our product from a professional manufacturer. The Urlinski company designs and manufactures the equipment for production of cosmetics and pharmaceuticals. Urlinski pointed out the problems associated with a preservative-free, biomaterial based product, which later turned out to be real problem, because some of our samples spoilt when stored at room temperature. We concluded that a bio-based product gets contaminated and degraded too easily, especially if the product is stored at room temperature and handled with bare hands. We also discussed about this problem with Andreas Lindberg and his suggestion was to store the product in the fridge instead of mixing it with synthetic materials. We later tested the affect of temperature on microbial growth in our samples and the results were a significant reduction in microbial growth.
Left and middle figures: Severely degraded 3 % Cekol 50000 W with medium exfoliant - hydrogel turned into cloudy liquid after 2 weeks; Right figure: Growing mold in 7 % Cekol 2000 with heavy exfoliant.
Due to the problem with microorganism growth in the hydrogels, we decided to check the effect of adding a preservative on the solution stability. We picked the benzyl alcohol for a trial, because it is used in a wide variety of cosmetic formulations [7]. According to Cosmetic Ingredient Review, it is safe to use in cosmetic products at concentrations of up to 5 %. However, in the European Union, benzyl alcohol is only allowed at a maximum concentration of 1 % in ready for use preparation [8].
On one hand, benzyl alcohol can be considered as a natural ingredient, as many plants, fruits, and teas have it as a component. On the other hand, the cheaper synthetic version is usually used in products, which is produced by mixing benzyl chloride with sodium hydroxide. Other ‘natural’ alternatives are also available and could be also considered in the future.
Benzyl alcohol is a colorless liquid and has a mild, pleasant aromatic scent, so it is used not only as a preservative but also as a fragrance ingredient. We assumed that our cosmetic product should be odorless or with subtle aroma. However, during testing benzyl alcohol as the preservative, we got annoyed with its perfumed smell. After mixing the components, the smell was not so irritating anymore, but it is important to consider the influence of preservatives and other additives on the finished product aesthetics such as odor, color and viscosity.
Moreover, the interaction of benzyl alcohol or other preservatives with the dermcidin should be investigated in the future to provide the anti-acne features of our product. The testing we carried out with benzyl alcohol turned out to be promising and within one week no microorganism growth was found in the hydrogel samples. In the future, more test are required and we were also taking into account the possible effect of sterilization of the beads and good manufacturing practice to avoid contamination.
Sterilized peach beads.
Package
In package design, we had several potential material candidates, like biodegradable polylactic acid (PLA), paper and wood. We decided to go with a wooden package, because we had a somewhat humorous idea of a wood based product packaged inside a wooden package. With a wooden package we also represented Finnish nature, which served as an inspiration in the whole design process. The final package is made out of flamed birch wood, which has a naturally beautiful structure and outlook. Our product name was laser engraved on top of the package and the ingredient information can be engraved on bottom of the package. In actual commercial production process, a wooden package will most probably be too expensive, but now we wanted to focus on a show piece, an idea of a beautiful package that can be used after the product has run out. With a wooden package we will likely also get more attention. In the future, the package could be a PLA tube or a coated paper tube which is easy to recycle or burn.
Making the package for prototype sample
Future Work
We had two possible paths to proceed with the application prototype in the time limits of iGEM competition. We had a possibility to make an early prototype product sample with the correct materials and compositions, or a look-alike product that effectively mimics the functionality of the final end product. We decided to to proceed with the look-alike product in order to have an understandable sample in the end to show and to create a visual, concrete concept around our research and product. Next steps with the product development would be to bring dermcidin and the hydrogel together and testing the activity in final product and how it works on skin.
Our aim was to not only to create an innovative and eco-friendly product by combining together a problem, synthetic biology and product design; another purpose of our product concept was to be able communicate about synthetic biology via our product and concept. We wanted to create a beautiful, easy to approach product concept and brand that has strong commercial potential. We created a business plan for our product which can be found here .
References
[1] Aslam, I; Fleischer, A; Feldman, S. 2015. "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs (Review). 20 (1): 91–101. Accessible at: [here].
[2] Walsh,T; Efthimiou, J; Dréno, B. 2016. Systematic review of antibiotic resistance in acne: an increasing topical and oral threat 16: e22–32. Accessible at: [here].
[3] Beylot, C; Auffret, N; Poli, F; Claudel,J.-P; Leccia, M.-T; Del Giudice, M.-T; Dreno, B. 2013. Propionibacterium acnes: an update on its role in the pathogenesis of acne Volume 28, Issue 3.March 2014
Pages 271–278. Accessible at: [here].
[4] Nakano, T; Yoshino, T; Fujimura, T; Arai, S; Mukuno, A; Sato, N; Katsuoka, K. 2015. Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris. 95(7):783-6. . Accessible at: [here].
[5] Das, S; Reynolds, R. 2014. Recent Advances in Acne Pathogenesis: Implications for Therapy Volume 15, Issue 6, pp 479–488. Accessible at: [here].
[6] Nguyen, C. M., Beroukhim, K., Danesh, M. J., Babikian, A., & Koo, J. (2016). The psychosocial impact of acne, vitiligo, and psoriasis: a review. Clinical, cosmetic and investigational dermatology, 9, 383.
[7] Nair B., 2001. Final report on the safety assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. Publication. Accessible at: [here].
[8] Benzyl alcohol - CosIng Database. Data sheet. Accessible at: [here].
