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. 2026 Mar 1.
doi: 10.1002/lsm.70115. Online ahead of print.

Comparative Evaluation of R134a and HFO-1234ze Cryogen Spray Cooling Using a Mouse Model With Controllable Epidermal Pigmentation

Wangcun Jia  1 , Yurie Jeong  1 , Crystal Huynh  1 , Oswald Lai  1 , Emily Nguyen  1 , Grant Swajian  2 , Jade Niu  1 , Ayana Kashikar  1 , Joshua Khaw  1 , Hong Pu  3 , Bernard Choi  1   4 , John D'Orazio  3 , J Stuart Nelson  1 , Bahman Anvari  2
Affiliations

Comparative Evaluation of R134a and HFO-1234ze Cryogen Spray Cooling Using a Mouse Model With Controllable Epidermal Pigmentation

Wangcun Jia et al. Lasers Surg Med. .

Abstract

Objectives: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance.

Methods: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1re/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold to suprathreshold injury conditions, with cryogen assignment randomized. Hypopigmentation at Day 7 served as the primary injury endpoint and was scored independently by three blinded raters. Surface cooling induced by each cryogen was measured separately using thin-film thermocouples on a skin phantom, and subsurface temperature distributions were estimated using one-dimensional transient heat-transfer modeling.

Results: Mean hypopigmentation scores did not differ significantly between R134a- and HFO-1234ze-cooled sites across the full range of pigmentation and fluence studied (p = 0.46). Heat-map analysis and regression modeling confirmed that hypopigmentation increased with fluence and darker pigmentation but was independent of cryogen type. Surface temperature measurements using skin phantom revealed that R134a produced more aggressive transient cooling than HFO-1234ze, reaching approximately 10°C lower minimum temperatures. However, numerical modeling of skin cooling using heat flux inferred from phantom measurement showed that this surface advantage decayed rapidly with depth, resulting in ≤ 2°C-3°C differences within the viable epidermis.

Conclusions: Despite differences in surface cooling magnitude, R134a and HFO-1234ze provided equivalent epidermal protection under clinically relevant conditions. These findings support HFO-1234ze as an effective, lower-GWP alternative to R134a for CSC in laser dermatologic applications.

Keywords: dermatologic laser surgery; hydrofluoroolefin; melanin; temperature measurement; transgenic mice.

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References

    1. J. S. Nelson, “Dynamic Epidermal Cooling During Pulsed Laser Treatment of Port‐Wine Stain: A New Methodology With Preliminary Clinical Evaluation,” Archives of Dermatology 131, no. 6 (1995): 695–700.
    1. J. S. Nelson, T. E. Milner, B. Anvari, B. S. Tanenbaum, L. O. Svaasand, and S. Kimel, “Dynamic Epidermal Cooling in Conjunction With Laser‐Induced Photothermolysis of Port Wine Stain Blood Vessels,” Lasers in Surgery and Medicine 19, no. 2 (1996): 224–229.
    1. W. K. Nahm, M. M. Tsoukas, V. Falanga, P. A. Carson, N. Sami, and D. J. Touma, “Preliminary Study of Fine Changes in the Duration of Dynamic Cooling During 755‐nm Laser Hair Removal on Pain and Epidermal Damage in Patients With Skin Types III‐V,” Lasers in Surgery and Medicine 31, no. 4 (2002): 247–251.
    1. H. A. Waldorf, T. S. Alster, K. McMillan, A. N. B. Kauvar, R. G. Geronemus, and S. J. Nelson, “Effect of Dynamic Cooling on 585‐nm Pulsed Dye Laser Treatment of Port‐Wine Stain Birthmarks,” Dermatologic Surgery 23, no. 8 (1997): 657–662.
    1. C. Chang and S. J. Nelson, “Cryogen Spray Cooling and Higher Fluence Pulsed Dye Laser Treatment Improve Port‐Wine Stain Clearance While Minimizing Epidermal Damage,” Dermatologic Surgery 25, no. 10 (1999): 767–772.

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