Hyposkin® human skin models

Live immune response to subcutaneous injection

The HypoSkin® live human skin model

First-in-human data generation for subcutaneous injections

HypoSkin® human skin models currently offer the closest alternative to directly injecting a compound in an actual person’s skin. They are designed to help drug and vaccine developers accelerate the selection of viable drug candidates. Thanks to our unique technology, the models help you obtain relevant and accurate first-in-human data when it comes to injection site reactions, immunology or metabolism. A quick overview of what HypoSkin® can do for you:

Immunocompetent

HypoSkin® models hold the features and functionalities of in vivo human skin, with all skin and immune cells, to generate predictive human data.

Standardized

The models are standardized for reproducible research and testing on real, live human epidermis, dermis and adipose tissue.

Injection

The HypoSkin® model is the only human skin model on the market to study live response to subcutaneous and intradermal injection.

Platform

HypoSkin® is suitable for a broad range of applications, from injection site reactions over medical devices to studying bolus injections.

Human immune response to your drug

A full week of testing opportunities

Due to the current lack of research tools to study response to injections in humans, the development of injectable therapeutics remains challenging, with animal testing as the only option. To date, Genoskin’s HypoSkin® model is the only human skin study platform in the world that allows studying subcutaneous and intradermal injection in humans without harming either humans or animals. HypoSkin® models provide crucial information on the response of real, live human skin and immune cells to drugs, vaccines and medical devices. The skin is bio-stabilized thanks to our patented technology, which allows keeping real human skin alive for 7 days. This approach helps us provide a highly relevant and reliable solution to pharmaceutical, biotech, cosmetic and chemical companies to test their compounds on and in real human skin for an entire week.

The HypoSkin® project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 816289 (SME Instrument).

Study human immune cell response to derisk drug development

Live human immune cells in their native environment

Mast cells
Mast cells
Natural killer cells
Natural killer cells
Macrophages
Macrophages
Neutrophils
Neutrophils
T-cells
T-cells
Langerhans cells
Langerhans cells

Human skin is much more than an excellent tool to study the response of structural cells, such as melanocytes, keratinocytes, sebaceous glands, etc., to formulations. Real human skin also possesses an extraordinary diversity of immune cells that are involved in drug-induced immunotoxicity (Tokura et al., 2021 & Kabashima et al., 2019). The immune cells we find in the skin (resident memory CD4 and CD8 T lymphocytes, dendritic cell subsets, innate lymphoid cells, natural killer cells, macrophages, mast cells, some B-cells and others… ) are also present in other human organs (Nguyen et al., 2019). In real skin, immune and structural cells constantly interact together to form a true ecosystem, which is key to apprehending human immunological response to drugs and formulations prior to clinical trials.

Dendritic cells
Dendritic cells
Basophils
Basophils
Innate lymphoïd cells
Innate lymphoïd cells
B-cells
B-cells
Eosinophils
Eosinophils
Monocytes
Monocytes

HypoSkin®, a flexible study platform for first-in-human data

Easy & relevant study results for research on injections

The HypoSkin® model contains live human epidermis, dermis and adipose tissue. It is the only model on the market that allows for research on subcutaneous injection in human skin, but it also is suitable for studies on infusion and intradermal injection of all types of biologics and small molecule drugs.

Photo showing subcutaneous injections on HypoSkin

Subcutaneous Injection & Infusion

Intradermal injection of HypoSkin

Intradermal Injection

A wide range of applications

Explore all the possibilities of immunocompetent human skin

The HypoSkin® model is suitable for a wide range of applications, including first-in-human efficacy and toxicity studies, prior to clinical trials. The model allows for in-depth immunology studies in order to provide a window to the immune response of the human body after drug or vaccine administration. Below, you’ll find some examples of the types of studies you can conduct with the HypoSkin® model.

Immunotoxicity

Immunoprofiling

Bolus injection

Medical devices

Dermal filler characterization

Bolus
Image of subcutaneous bolus injection of 100µL of contrast agent in the HypoSkin® model at D1. The image illustrates the validity of the HypoSkin® model in terms of homogeneous diffusion, similar to what would happen in a human test person. Images were acquired in collaboration with Laurent Malaquin – EliA Group – LAAS CNRS & Paul Duru – Toulouse Institute of Fluid Mechanics

Scientific validation in terms of skin structure

Human skin structure is maintained for 7 days

Since it is real human skin, HypoSkin® has the same structure and composition as in vivo human skin. Hematoxilin & Eosin staining shows that the tissue and cellular structures of all three skin layers (i.e. epidermis, dermis and hypodermis) are preserved. The images reveal a mature stratum corneum, a dermal-epidermal junction with the same key features as real human skin, a preserved basal layer and rete ridges. The images also illustrate that HypoSkin® integrity is preserved for up to 7 days.

HypoSkin Epidermis & Papillary Dermis - Day 0
Epidermis & Papillary Dermis - Day 0
HypoSkin Epidermis & Papillary Dermis - Day 3
Epidermis & Papillary Dermis - Day 3
HypoSkin Epidermis & Papillary Dermis - Day 7
Epidermis & Papillary Dermis - Day 7
HypoSkin Reticular Dermis - Day 0
Reticular Dermis - Day 0
HypoSkin Reticular Dermis - Day 3
Reticular Dermis - Day 3
HypoSkin Reticular Dermis - Day 7
Reticular Dermis - Day 7
HypoSkin Subcutaneous tissue - Day 0
Subcutaneous tissue - Day 0
HypoSkin Subcutaneous tissue - Day 3
Subcutaneous tissue - Day 3
HypoSkin Subcutaneous tissue - Day 7
Subcutaneous tissue - Day 7

Scientific validation in terms of immune cell presence

Functional & activatable human immune cell response

Thanks to Genoskin’s proprietary technology, all skin-resident immune cells remain functional for over a week during experimentation. In the image below, HypoSkin® immune cells are characterized using our dedicated MANTIS® spatial biology platform. As shown in the image, HypoSkin® contains a normal, functional and activatable population of immune cells, including myeloid cells (Langerhans, Dendritic cells, Mast cells, Macrophages…).

Diversity of myeloid cells in HypoSkin® at D1 of culture. Acquisition made thanks to our proprietary spatial biology solution, MANTIS and using the Myeloid Cells panel

Diversity of myeloid cells in HypoSkin® at D1 of culture. Acquisition made thanks to our proprietary spatial biology solution, MANTIS and using the Myeloid Cells panel (markers: CD45 – CD1c – CD207 – Tryptase – HLA-DR – Siglec 8 – CD123 – MPO – CD68).

Single Cell RNA sequencing on HypoSkin

Analysis of the main cell subpopulations found in HypoSkin® at D1 of culture. After RNA extraction from HypoSkin®, we analyzed the model with Next Generation single cell RNA sequencing. 15,000 cells and more than 9,000 genes were analyzed.

Example of application

Toxicity assessment services

Immunotoxicity

Local immune burst & inflammatory event associated with skin-resident immune cell or mast cell activation is mostly caused upon injection of biologic drugs.

Cytotoxicity

Local toxicity causing cell death and necrosis is mostly caused upon injection of small molecule drugs.

Contact Us

Should you need more details on our HypoSkin® model and its applications, don’t hesitate to contact us.

Scientific publications using HypoSkin®

See how others use the HypoSkin® model to generate results

August 2022 - Immortalized human myoblast cell lines for the delivery of therapeutic proteins using encapsulated cell technology

November 2021 - A suspended layer additive manufacturing approach to the bioprinting of tri-layered skin equivalents

July 2021 - Poster - Mitigation of Injection Site Reactions after Subcutaneous Administration of Dalcinonacog Alfa (DalcA) in Hemophilia B Using Preclinical Models

July 2021 - Poster - Assessing subcutaneous injection site reactions by leveraging immunocompetent human skin and artificial intelligence

December 2020 - Standalone or combinatorial phenylbutyrate therapy shows excellent antiviral activity and mimics CREB3 silencing

August 2019 - Near-infrared light activable hydrogels for metformin delivery

  • Near-infrared light activable hydrogels for metformin delivery
    • Published in Nanoscale – 2019 Aug 29;11(34):15810-15820
      • Li Chengnan, Quentin Pagneux, Anna Voronova, Alexandre Barras, Amar Abderrahmani, Valérie Plaisance, Valerie Pawlowski, Nathalie Hennuyer, Bart Staels, Lea Rosselle, Nadia Skandrani, Musen Li, Rabah Boukherroub, Sabine Szunerits

December 2018 - Poster - A fully functional ex vivo human skin model to study human skin microbiome

January 2018 - Poster - Evaluation of local inflammatory reactions following subcutaneous injection of a pro-inflammatory cocktail in a fully human ex vivo skin model

Not sure if HypoSkin® is the model you need?

Don’t hesitate to get in touch to explain your project. Our experts are here to help you out.