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Peripheral Nervous System Tissue Engineering for Medical and Cosmetic Testing Applications

Periodic Reporting for period 2 - PLATFORMA (Peripheral Nervous System Tissue Engineering for Medical and Cosmetic Testing Applications)

Reporting period: 2021-10-01 to 2022-09-30

What is the problem being addressed?
Advances in the treatment of many human health conditions depend on access to representative testing systems that allow researchers to quickly evaluate the potential of new drug therapies. In some fields, the options are limited and efforts to reduce the amount of animal testing used are also creating a strong need to find better solutions. In the field of research focused on Amyotrophic lateral sclerosis or ALS, a progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, there are a distinct lack of model systems that are sufficiently representative of the human condition which is hindering the investigation and development of effective treatment options. Similarly in the field of cosmetic testing, previously very reliant on animal testing, better and better alternatives are needed to ensure that cosmetics are developed that reach the highest safety standards possible.

Why is it important for society?
The average incidence rate of ALS worldwide is about one in 50,000 people per year that equates to about 5,760 to 6,400 new diagnoses per year. According to some estimates, the number of cases of ALS in the world will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. The largest increase will be seen in Africa with 116%, followed by Asia with 81% and South America with 73%. ALS is fatal. The average life expectancy after diagnosis is two to five years, but some patients may live for years or even decades. (The famous physicist Stephen Hawking, for example, lived for more than 50 years after he was diagnosed.)

Testing represents an important part of a cosmetic product registration process. Cosmetic products have to undergo all the required testing defined in the EU Cosmetics Regulation (EC) 1223/2009 in order to be compliant and more importantly, to prove they are safe for use under reasonably foreseeable conditions.

What are the overall objectives?

Skin Module will be a world first, a commercially available innervated human skin tissue model. It allows studies and testing of Peripheral Nervous System (PNS) responses to external stimuli in a physiologically relevant context. This module itself can be used to investigate activities of both dermal and nerve cells at the same time. When a stimulus is introduced on the skin layer, responses of skin cells and activities of sensory neurons (e.g. pain & itch) can be recorded simultaneously. The Applications of the Skin Module are as follows:

• Peripheral neurotoxicity testing of cosmetics, pollutants, and transdermal delivery of new therapeutics, etc.
• Development of wound healing assays and wound healing therapeutic strategies
• Studies of interactions of human sensory neurons and dermal tissue

Muscle Module is an innovative motor neuron-skeletal muscle tissue model. It allows non-invasive recordings of neuromuscular transmission in real time. The Applications of the Muscle Model are as follows:
• Investigation of human neuromuscular junction formation and signal transmission upon administration of therapeutic agents.
• Studies of muscular atrophies & motor neuron diseases with genetically engineered or patient derived cells.
• Long-term monitoring and analysis of drug effects (toxicity and efficacy) with live 3D imaging and electro-physiological recordings.
PLATFORMA has achieved significant results over the two years of endeavour. The beneficiaries have succeeded in developing a fully functional assay ready model for the motor neuron-muscle 3D module, this model displays functional neuromuscular junction characteristics and is able to show functional differences between ALS motor neurons and wildtype neurons when controlling muscle contractility. Miniaturizing the motor neuron module to a 48 well format has also made this a commercially viable system leading to engagement in the market with customers for the motor neuron-muscle module. The sensory -skin module demonstrates sensory neuron / skin innervation but due to its complexity still requires further development, for cell environmental support and sensory neuron growth and connections to the skin layer. Trialing the use of /HaCat cells instead of Keratinocytes to mitigate some issues has yielded positive results which will be explored beyond the funded period of the project.

COMMUNICATION, DISSEMINATION and EXPLOITATION –The promised impacts at the end of the project have not been realized in full. The Muscle-Motor Module has achieved expected levels of technology readiness, but the Skin-Sensory Module has not been able to resolve problems in getting interconnections between all of the layers. Nevertheless, the potential in the Muscle-Motor Module is already being pursued in the marketplace by and it is hoped that a scaffold, cells, media package will be marketed to interested users in the future. The development of the 3D scaffolds has reached the expected level of technology readiness, but the Photonic characterisation system has been hampered by too many cell culturing challenges, meaning validation is not complete.
The Skin Module will be championed by partner StratiCELL who have the belief in the concept, expertise, and relevant market knowledge to convert latent and explicit customer interest into downstream demand facilitated by the development of a skin-sensory assay for cosmetic and dermatologic testing. This project is offering disruptive testing services for early discovery and preclinical studies related to sensory skin disorders. The services will be used to screen efficacy of compounds but also topical formulations and finished products, enabling simultaneous testing of more compounds at lower cost and characterization of their mechanisms of action. This offer can also be customized to each customer’s case. The development of the Skin Module is aligned with the EU’s directive of eliminating animal models in cosmetics testing and reducing such use in drug development. The human Skin Module will be the world’s first commercially available in vitro innervated skin testing platform allowing StratiCELL to contribute in the development of a new market in cosmetic testing (sensorial-related wellbeing and sensitive skin) and offering highly relevant alternative testing offers for drug development (itch and pain).

The Muscle Module will be championed by partner Axol who have identified an urgent market need amongst pharma-biotech companies for disease-relevant human neuro-muscular models in physiologically relevant 3D culture, as well as instant functional read-out on drug responses. Amyotrophic lateral sclerosis (ALS), a progressive fatal motor neuron degenerative disease affecting 222,801 patients in 2015 globally, is of particular interest amongst Axol’s current customers.
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