A cryomicroneedle patch ready for deployment.
A cryomicroneedle patch ready for deployment.
Source: Chang et al. /DOI number: 10.1038/s41551-021-00720-1

Cryomicroneedles for intradermal therapeutic cell delivery

A research team led by City University of Hong Kong (CityU) scientists recently developed a new generation of microneedles technology which allows the intradermal delivery of living cells in a minimally invasive manner.

Their experiment showed that vaccination using therapeutic cells through this ground-breaking technology elicited robust immune responses against tumours in mice, paving the way for developing an easy-to-use cell therapy and other therapeutics against cancers and other diseases.

The new technology "cryomicroneedles" are the icy microneedles shorter than 1 mm and can deliver therapeutic cells into the skin layers. "It is a skin patch-like device that can load, store, and intradermally deliver the living mammalian cells," explained Dr Xu Chenjie, Associate Professor at the Department of Biomedical Engineering (BME) at CityU.

Cell therapy, also called cell transplantation, is a therapy in which living cells like immune cells or stem cells are injected, grafted or implanted into a patient to achieve a medicinal effect. Advances in cell therapies have brought promising treating approach for previously intractable diseases like cancers. "But many problems related to the application of cell therapy yet to be solved," said Dr Xu. 

For example, the therapeutic cells are currently delivered by either surgical grafts or bolus injection. These methods are invasive, painful, complicated, low-efficient, and they bring the risk of infection and require experienced professionals to implement. It is also hard to store and transport the current solution-like formulations of cell therapeutics.

Schematic illustration of the transdermal delivery of cells using...
Schematic illustration of the transdermal delivery of cells using cryomicroneedles.
Source: City University of Hong Kong

To solve this challenge, Dr Xu and his team at CityU have developed these cryomicroneedles that carry and deliver living cells into the skin. By putting the patch-like device on the skin, the microneedles would penetrate through the skin, detach from the patch base and then melt. The loaded cells were released, and subsequently migrated and proliferated inside the skin. This innovative device can be stored for months in refrigerators. It is also easy for transportation and deployment.

As a proof-of-concept, the researchers explored cell-based cancer immunotherapy through intradermal delivery of ovalbumin-pulsed dendritic cells. In the study, vaccination with this device elicited robust antigen-specific immune responses and provided strong protection against tumour in mice, which were superior to the therapeutic outcomes by conventional standard vaccination methods such as subcutaneous and intravenous injection.

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"The application of our device is not limited to the delivery of cells. This device can also package, store, and deliver other types of bioactive therapeutic agents, such as proteins, peptides, mRNA, DNA, and vaccines. I hope this device offers an easy-to-use and effective alternative method for the delivery of therapeutics in clinics," Dr Xu said.

The research was published in Nature Biomedical Engineering.

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