Skin Science

Research Blog

Question and Answer session with our General Manager

Some key questions were posed to our General Manager, Alex Chapman to find out his thoughts on his role, the company and Labskin. We managed to find some time with him in his busy schedule and ask these questions………

Describe your typical day as the General Manager at Innovenn.

A typical day is extremely varied and depends on what customer interactions are occurring at the time and will influence the whole day, but generally there is usually a mixture of working through projects with different customers, which can all be at various stages from initial conversations through quotes to reporting. There is quite a lot of work required on reviewing the financial aspects of supplying services and Labskin to large companies, this can take quite a lot of time. Internally, I keep the team up to date with the various external activities and respond to any internal issues that arises. I am also actively involved in the Sales and Marketing aspect of the company where I produce and update marketing material such as application notes, the website and things like that.

What has surprised you the most since starting at Innovenn?

The most surprising aspect since joining would be the amount of work required on evaluating and continually assessing the company’s finances. There is a lot more interaction with our parent company Integumen and our suppliers and customers, which I didn’t appreciate beforehand.

What is your favourite part of your role?

I’m still relatively new to the role and this area of science, but there is always something new to address. It can sometimes it can be frustrating, particularly when you need to resolve issues revolving around the shipment of Labskin into certain countries, but I love learning something new and this job provides me with that opportunity.

What do you see Innovenn becoming and evolving into?

For me, our unique offering of our in-depth understanding of Labskin makes it an ideal research tool so I see Labskin and Innovenn becoming a key research partner for our customers. We are already moving into the direction of using the model to assess skin metabolism and drug penetration, as well as creating healthy and diseased models. I truly believe our future will be providing the model to the scientific community as a medium throughput in-depth research platform.

Conference attendance in June 2018

Innovenn has been extremely busy recently and managed to attend three different conferences around the world in 10 days. We were fortunate to be at the 3D Cell Culture 2018 conference in Freiburg (Germany) as well as the Advanced Cell Culture: A Practical Approach conference in London (UK). We also presented at Lucideon’s Innovation for Industry Forum – Advancing Formulations in Stoke-on-Trent (UK).

Both the cell culture conferences highlighted the work being conducted into developing more complex in vitro models to help the drug discovery stages of the R&D process in the pharmaceutical industry. There was an emphasis on creating organoid’s by exposing cells (e.g. stem cells) to artificial signalling microenvironments in constructs, which mimic organs. There were sessions based on increasing the complexity of skin models to incorporate immune cells (macrophages) as well as integrating a skin model with a two-organ-chip containing endothelial cells to create a vascularised skin equivalent model.

However, the forum at Lucideon highlighted how the personal health care industry is trying to create products for a global market. Companies are trying to develop new products with core key ingredients, which can be adjusted in concentration to satisfy all their customer’s desires, needs and wants around the world within a fast-paced environment.

Here at Innovenn, we are always excited to hear what is happening in the scientific community and there is no better way than by attending conferences.

Current research into skin conditions/diseases – Part 2

The incidences of skin cancer across the world continue to rise annually where 95% of these cancers are caused by the transformation of normal melanocytes into melanoma cells and transformation of epidermally derived cells into non-melanoma skin cancers, including basal cell carcinomas. Keratinocyte carcinomas (KCs) are the most common malignancies worldwide and exceed the combined prevalence of all other cancers. It has been shown that prolonged UV light exposure is the most common cause for developing skin cancer along with genetic and environmental factors. There is a lot of research looking into the underlying molecular mechanisms of the disease to help with the development of new drugs and therapies.

New biologics are currently being developed, which target specific pathways in the cells to encourage the body’s immune system to remain active and kill the cancer cells. Other biologics are focusing on targeting proteins, which are being expressed by the cancer cells to block them from growing or spreading to other parts of the body. Therefore, identifying molecules, which encourage cancer progression and developing ways to disable them through the development of new drugs, is crucial in tackling advanced tumours. Pharmaceutical companies are spending hundreds of millions ($) on developing new cancer drugs with several new ones in the latter stages of clinical trials.

Current research into skin conditions/diseases – Part 1

Approximately 2-3% of the world’s population suffering with psoriasis or some form of eczema such as atopic dermatitis whereas, approximately 20 % of children around the world have eczema. Currently, there is a lot of research being conducted to obtain a greater understanding of mechanisms involved in atopic dermatitis and psoriasis to help people suffering from these chronic conditions. Research has shown that even though psoriasis and atopic dermatitis share similarities where both diseases exhibit dermal changes, influx of immune cells in the dermis and lower epidermis as well as epidermal hyperkeratosis, there are distinct immunological differences. New research has shown cytokines IL-23/IL-17A play an important role in plaque psoriasis whereas, cytokines IL-4 and IL-13 have been found to have a prominent role in atopic dermatitis. The new knowledge gained through these studies have allowed for the development of new drugs to inhibit specific cytokines produced by the immune response. Big pharmaceutical companies are driving the development of new drugs targeting the immune response and there are several going through the various stages of clinical trials. This means there is a vast amount of work being conducted to create and identify novel immunologic molecules thought to be relevant in patients with atopic dermatitis, which may provide targeted therapies within the next few years. All the research investigating the diseases to identify key mechanisms and molecules involved will allow the development of new anti-inflammatory drugs that could be either stand-alone treatments or be combined with existing therapies.

All this research into these diseases will help alleviate the symptoms experienced by the millions of sufferers around the world.

Our Team

We are extremely fortunate to have staff members who have over 10 years’ experience in producing our living skin equivalent model called Labskin. Here at Innovenn, we provide a unique experience where we have a truly multi-disciplinary environment where all members work alongside each other. This allows the company to combine all the relevant expertise across multiple disciplines in one place where we are able to discuss cell biology, microbiology and chemistry in depth, which in turn creates an innovative team. We are privileged to have a team consisting of 7 highly trained scientists who all have specialisms in skin biology. This environment allows us to discuss and apply our individual experiences to improve Labskin through the development of more complex models as well as applying the best technique to analyse these.

We have several team members who have worked to numerous regulatory standards (ISO 9001, GLP, GMP and UKAS), whilst other members have worked extensively in academic institutions. This diversity in the team allows an open and creative environment, whilst using the best regulatory practices set out by our own quality assurance manager.

With all the diverse and skilled team members working at Innovenn means we are able to continually develop and improve our model as well as our services to suit any need.

 

 

 

 

 

 

 

 

 

Reasons behind 3D in vitro models

Using in vitro models are important tools for biological research and cell-based assays to predict drug activity, metabolism and toxicity in vivo. 2D monolayer culture systems have become extremely important as in vitro tools within the pharmaceutical industry at the drug discovery stage of their research and development programme. This is purely down to the assay being simple, fast, cost effective and reducing the number of animals being used within the study. The low percentage (approx. 10%) of compounds actually progressing through clinical stages of drug development has been linked to the lack of clinical efficacy and/or unacceptable toxicity. It has been shown that a portion of these failures at phase III clinical trials lead back to the cellular responses to the drug obtained from the 2D systems as they do not represent in vivo responses. The cells within in vivo environments are mostly surrounded by other cells and encased within extracellular matrix creating a three-dimensional setting, these monolayer cultures lack the native 3D environment.

These subsequent drug failures to market have led to the development of 3D in vitro models, which allows cells to grow or interact with their three-dimensional surroundings as cell are embedded within an artificial scaffold to mimic the in vivo environment. Numerous studies have shown cells grown within in 3D in vitro models to be more physiologically relevant and with improved biological functionality. The cells in these models mimic in vivo cellular morphology, proliferation, differentiation, response to stimuli, drug metabolism, gene expression and protein synthesis as well as general cell function.

Living skin equivalent models, such as Labskin provide a more realistic in vitro environment where they are able to provide a better representation of biological responses compared to in vivo skin.

Possible models created with Labskin

Due to Labskin consisting of a co-culture of primary dermal fibroblasts and keratinocytes, the model provides an excellent platform to create more complex models. Here at Innovenn, we are in the process of increasing the model complexity and become a promising alternative to immunologically different in vivo models and scarce ex vivo skin explants.

Two years ago, Labskin was treated with a cytokine (IL-22) to induce psoriatic skin by mimicking the inflammatory response. Additionally, a cytokine cocktail (IL-4, IL-13, TNF-α and IL-31) was added to another in vitro skin model managed to induce atopic dermatitis like features. Other atopic dermatitis models have tried to obtain a better representation of the chronic disease where lymphocytes were added to the model to induce the disease condition.

Other living skin equivalent models have also been modified to mimic melanoma (a type of skin cancer). The addition of human malignant melanoma cells with the keratinocytes within the model has shown to closely follow the progression of melanoma in vivo.

These more realistic diseased models provide a fantastic platform to study and obtain a greater understanding of the disease whilst being used as a tool to develop therapeutic treatments for these conditions. As we are continually developing our Labskin model and you have any suggestions about what type of model you would be interested in working with, please do not hesitate to contact us via our email on the website.

Ways to analyse Labskin

We thought it would be great to write a little segment on the different ways to analyse Labskin to obtain a better picture of the information, which can be gathered from Labskin. The amount of information gained from analysing Labskin is phenomenal, particularly recently with the rapid development of high throughput techniques such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. These techniques provide a deeper understanding the changes are occurring at the gene, transcription, protein and metabolite level in the skin when Labskin has been altered in any way e.g. the addition of products/microflora to the Labskin. The integration of multi-omic data and joint modelling allows a greater understanding of the Labskin’s systems biology interaction with a particular drug or micro-organism.

Labskin can also be assessed by different types of microscopy including light, fluorescence, scanning electron and transmission electron microscopy. This type of analysis is able to provide anatomical, immunological and biochemical information by imaging specific areas in tissues, such as Labskin by using appropriately-labelled antibodies to bind specifically to their target antigens in situ. This type of information provides the spatial relationship of labelled proteins throughout the tissue sample. Additionally, inflammatory responses from Labskin can be easily analysed by an enzyme-linked immunosorbent assay (ELISA) where proteins, such as cytokines have been secreted into the media.

A vast array of biological information may be obtained from the analytical techniques described above but analysis of Labskin is not limited to only these techniques.

Benefits of using Living Skin Equivalents

There are substantial benefits of using living skin equivalent (LSE) models, such as Labskin. These models have the potential to accurately assess the skin’s biological processes to a wide variety of different stimuli/products including but not limited to cosmetics, pharmaceuticals, sun creams, wound dressings and wound therapies. These models are able to investigate the effect of chemical corrosiveness on the skin, phototoxicity of substances and toxicity of various chemicals without the need of testing on animals.

LSEs are a cost effective, viable alternative to animal testing and are capable of providing a reliable screening platform to test drug penetration across the epidermis into the dermal layer. This has become particularly important to new chemicals being released within the EU as there are regulations in place, which prohibit the development and testing of cosmetic and pharmaceutical ingredients on animals.

These models are highly flexible in their use as they are able to create a variety of experimental conditions in one single platform. Also, LSEs are produced within the laboratory in a controlled environment therefore, reducing model variation between and within batches. Another benefit of using LSE models is that they are created with human primary cells and it has been scientifically reported pre-clinical studies using rodents and other small animals have limited biological translation to humans due to differences in their biological responses/structure. For examples, there are differences in the anatomy, hair abundance and in the process of healing wounds (human skin heals via the re-epithelialisation through the migration of keratinocytes whereas, rodents heal wounds by contracting the wound site).

All these factors highlight the huge benefits LSE models have to the research and regulatory community within a laboratory setting.

Attendance to Wounds UK Infection Day and 5th SIG Mass Spectrometry Imaging Symposium

The week commencing the 16th April, Innovenn was lucky enough to present at the 5th SIG Mass Spectrometry Imaging (MSI) Symposium at Sheffield Hallam University and attend the Wounds UK Infection Day at York Racecourse.

The MSI Symposium gave a fantastic overview of the latest research being conducted across the world in both academia and industry. There were subtle differences in the use of MSI in research between industry and academia. There was definitely an emphasis on MSI as part of a complimentary analysis technique in a multimodal approach to discover a drug’s mode of action whereas, academia is advancing the technique to get the best spatial resolution and optimising deposition and ionisation strategies to detect a wider range of analytes. The diversity in the information gained from using this technique was highlighted in all the talks and posters presented at this thought provoking conference. We would also like to congratulate Cristina Russo from Sheffield Hallam University for winning best poster, especially as her PhD is using Labskin to assess the quantitation limits of MALDI-MSI.

We attended the Wounds UK Infection Day as delegates and we were extremely fascinated to hear about all the research going on at hospitals to help alleviate wound infections. There were a lot of discussions on the antibiotic resistance crisis and implementing new strategies to prevent surgery site infections by improving the perioperative care (thorough skin preparation prior to surgery and antibiotic administration immediately after surgery). There was a definite key message to take home highlighting wounds are dynamic environments and preventative is better than cure.

Here at Innovenn, we love being involved in current research and listening to all the novel work being conducted around the world.

Potential applications of Labskin

Our product, Labskin, is extremely versatile and can be used for a number of different applications. We are fortunate enough to be able to conduct research in-house as well as collaborating externally with research partners. The number of publications in peer review journals using Labskin, highlight the diversity and adaptability of Labskin in a variety of applications in which Labskin may be used for in research. In-house service facilities and external projects have used Labskin to test the potency of product ingredients and formations as well as drug penetration efficacy. However, recently there has been particular interest in understanding the interactions between the product and cultured microflora on Labskin. These more complex models provide a better representation of human skin through mimicking natural skin microflora or opportunistic pathogenic strains in a controlled environment. Therefore, providing more realistic in vitro alternatives to animal testing.

Our external collaborations have used Labskin to assess the product’s responses along side in depth cellular responses. These responses have been explored either directly through genomic and proteomic analysis or in-directly through secretion analysis. Enzymatic activity in Labskin have been assessed after the application of specific drug compounds, which was then compared against ex vivo human skin to create a xenobiotic metabolism database. Additionally, Labskin has been used as a platform for wound healing biomarker discovery, which may be used to help identify whether a wound is starting to heal or develop into an infected/chronic wound.

The diversity and versatility of the use of Labskin provides an excellent in vitro platform to explore human skin responses within a laboratory setting.

In-house R&D programme

As a company, we are extremely fortunate to have multi-disciplinary research amenities where we are able to combine cell culture and microbiology facilities next to each other. This allows us to conduct numerous in-house research and development programmes to test Labskin’s capabilities within a novel environment. Recently, we have been particularly focused on creating models with different microflora on Labskin to create more realistic in vitro skin models. Projects have included creating models, which mimic human in vivo pathogenic fungal colonisations (Dermatophytes) on the skin or human native bacteria. At the minute, there is a global interest in the benefits of applying prebiotics to aid growth or activity of beneficial microorganisms on the skin to recalibrate the skin to a create healthy microbiome. We have been involved in some fascinating projects where we are simulating the effects of different prebiotics on Labskin inoculated with various strains of bacteria.

Over the last couple of years, we have also developed a model to replicate the initial wound healing response and create an infected model, which simulates the processes found in vivo. From this project we were able to identify wound healing markers, which help identify whether a wound is healing in a clinical setting. We are extremely pleased with these results and these have been recently accepted in the International Journal of Cosmetic Science. Following the success of the project, the model is being developed further to create a wound consisting of biofilms to replicate chronic wounds.

We are proud of all the in-house projects we have undertaken and looking forward to unravelling all the capabilities Labskin has to offer and creating new and varied models.

External Collaborations

Labskin is currently being incorporated into some fantastic projects in research institutes around the UK. Following previous successful projects using Labskin at Sheffield Hallam University, we continue with our collaboration with Professor Malcolm Clench. There are currently three PhD projects, which all use Labskin to assess drug penetration, drug metabolism and cancer development. The drug penetration project is coming to an end and has generated novel results quantitatively assessing fungicide penetration through the epidermis using different product formulations. This work is currently being written up to be published in the very near future and we are extremely excited with the results. We will keep you updated with all the developments of the paper once it has been accepted and published.

Since last year, we have been working with Dr Raechelle D’Sa from the University of Liverpool on a project using Labskin to test innovative antimicrobial bandages for the treatment of wound infections. The project wants to assess the efficacy of bandages containing nitric oxide releasing nanoparticles on wounded and infected Labskin. This project is still in its infancy and preliminary work is still being conducted but we are extremely happy to be involved with this.

As a company, we are thrilled about all the projects being undertaken at the minute with Labskin and cannot wait for all the new results being generated.

 

 

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