Simulating High-Altitude Hypoxic Conditions Delays Wound Healing In Rats

Siyuan Cai; Guang Yao; Liheng Lin; Zijian Chen; Jin Linbo; Ziyi Zhou; Shiqi Zhou; Pinwen Wang; Zhen Cai; Dongli Fan; Yuan Lin; Yiming Zhang

doi:10.3791/71250

Research Article

Simulating High-Altitude Hypoxic Conditions Delays Wound Healing In Rats

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DOI:

10.3791/71250

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June 5th, 2026

Siyuan Cai^*¹^,²^,³^,⁴ , Guang Yao^*²^,³^,⁵^,⁶ , Liheng Lin^*⁷ , Zijian Chen¹ , Jin Linbo¹ , Ziyi Zhou¹ , Shiqi Zhou¹ , Pinwen Wang¹ , Zhen Cai⁴ , Dongli Fan¹ , Yuan Lin²^,³^,⁵^,⁶ , Yiming Zhang¹

¹Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, Army Medical University, ²School of Materials and Energy, University of Electronic Science and Technology of China, ³State Key Laboratory of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, ⁴Department of Plastic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, ⁵Shenzhen Institute for Advanced Study, University of Electronic Science and Technology of China, ⁶Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, ⁷Department of Anesthesiology, The First People's Hospital of Longquanyi District

^* These authors contributed equally

Summary

This study developed and preliminarily validated a rat model of delayed wound healing under high-altitude hypobaric hypoxia conditions.

Abstract

High-altitude hypobaric conditions may cause prolonged wound hypoxia and impaired healing, yet standardized models remain scarce. In this study, we developed a wound delayed healing model and preliminarily validated it by simulating high-altitude hypoxia using a controlled hypobaric system. Rats were housed at simulated altitudes of 3000 m (air pressure: 70.1 kPa, partial oxygen pressure: 14.7 kPa) to 8000 m (air pressure: 35.6 kPa, partial oxygen pressure: 7.5 kPa) to determine safety thresholds, with oxidative stress and skin hypoxia assessed. Results showed increased mortality risk at simulated 6000 m altitude, with tolerance observed below 5000 m. Elevated altitudes were associated with worsening oxidative stress and increased skin hypoxia; exhibited altitude-dependent delays in wound healing, reduced perfusion, suppressed collagen remodeling, and exacerbated inflammatory responses. Despite upregulation of vascular regenerative factors, microvascular density decreased. Overall, this study developed and preliminarily validated a rat model suitable for investigating mechanisms and interventions in high-altitude hypoxia-induced chronic wounds.

Introduction

Skin wound repair presents a widespread and significant clinical challenge. From acute trauma to various types of non-healing wounds, these conditions impose a persistent burden on healthcare systems and patients' quality of life¹^,²^,³^,⁴^,⁵^,⁶. Wound healing is not a singular event but a highly coordinated, overlapping multistage process: inflammatory cells, stromal cells, keratinocytes, and the microvascular system collectively rebuild barriers and remodel tissues under ....