Needle-free cutaneous delivery of living human cells by Er:YAG fractional laser ablation

ABSTRACT

Background: Dermatological diseases, including most skin cancers and rare genetic conditions frequently originate in the epidermis. Targeted, topical cell-based therapy is a promising therapeutic strategy. Here, we present the first report demonstrating that fractional laser ablation enables local ‘needle-free’ intraepidermal delivery of living human cells.

Methods: The cells penetrated porcine ear skin via microchannels created by Er:YAG fractional laser ablation; cell delivery was quantified using a haemocytometer. Cutaneous distribution was confirmed visually by laser scanning confocal microscopy and histological analysis.

Results: Total cell delivery (sum of amounts permeated and deposited) after 24 h increased from 5.7 ± 0.1 x10⁵ to 9.6 ± 1.6 x10⁵ cells/cm² when increasing pore density from 300 to 600 pores/cm², – corresponding to 19- and 32-fold increases over the control. At 600 pores/cm², cell deposition was 136-fold greater than cell permeation – the latter most likely due to transport from micropores into appendageal pathways. Production of GFP post-delivery confirmed cell remained viability.

Conclusion: The results demonstrate the feasibility of using controlled laser microporation to achieve local ‘needle-free’ cutaneous delivery of living human cells to the epidermis and dermis. This raises the possibility of using this technique for targeted new approaches for dermatological therapy in these regions.

KEYWORDS:

• Topical delivery
• Er:YAG laser
• fractional laser ablation
• epidermis
• living cells
• cell therapy
• skin

Acknowledgments

We thank our colleagues Prof. Urs T. Ruegg, Dr. Olivier Dorchies and Ophélie V. Pattey (Pharmacology group, School of Pharmaceutical Sciences, University of Geneva, Switzerland) for technical assistance with the histochemical studies. We would like to thank Prof. Leonardo Scapozza, Dr. Remo Perozzo and Dr. L Pernot (Pharmaceutical Biochemistry group, School of Pharmaceutical Sciences, University of Geneva, Switzerland) for reviewing the manuscript and providing the HEK-GFP cells, respectively. Finally, we would like to acknowledge our colleague Dr. Yogeshwar Bachhav for help with the laser device and Dr. Arne Heinrich (Pantec Biosolutions AG) for laser technical support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Swiss Commission for Technology and Innovation (CTI: 9307.1 PFLS-LS) Pantec Biosolutions AG and the National Natural Science Foundation of China (Grants No. 31200640/C0508 and 21135004/B050901).