The effects of hypoxia environment at high-altitudes on inflammation and angiogenesis in wound healing process:A meta-analysis and review

BACKGROUND: High-altitude hypoxia increasingly draws attention for its effects on wound healing. Because oxygen critically regulates inflammation and angiogenesis, hypoxic conditions often delay tissue repair. However, studies disagree on how hypoxia specifically alters inflammatory pathways and angiogenic responses. To resolve these discrepancies, we performed a systematic review and meta-analysis synthesizing existing evidence to quantify the impact of high-altitude hypoxia on inflammation and angiogenesis during wound healing. OBJECTIVE: To systematically investigate the impact of low-oxygen environments at high altitudes on wound healing and to establish a theoretical basis for developing wound-care and intervention strategies suitable for high-altitude conditions. DESIGN: Meta-analysis and Review. SETTINGS: Wound Healing in Hypoxic Exposure at High-Altitudes. PARTICIPANTS: 8 studies. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL). We included Randomized controlled trials and animal experiments on plateau hypoxia exposure and wound healing from the early years to 11 January 2026. Two researchers independently checked the literature, extracted data and assessed quality. We analyzed the data using RevMan 5.3 and sensitivity analysis to evaluate heterogeneity and robustness using one-by-one exclusion. RESULTS: We included 8 studies in the meta-analysis, we found that wound healing rate of high altitude group was lower than control group (SMD = -3.31, 95% CI -4.72 to -1.91, P < 0.05) and CD31 expression was lower in high altitude group than control group (SMD = -2.57, 95% CI -4.31 to -0.83, P < 0.05). Sensitivity analysis showed robustness. Pool effect size of IL-1β did not differ significantly between the groups (SMD = 1.47, 95% CI -2.4 to 5.36, P > 0.05). CONCLUSIONS: Current evidence from animal models suggests an association between high-altitude hypoxia and delayed wound healing, which may be linked to reduced expression of the angiogenesis marker CD31. The role of specific mediators like IL-1β remains unclear due to inconsistent findings across studies. Overall, the existing research, which is limited in both scope and methodological diversity, precludes definitive conclusions. This suggests that in high-altitude clinical settings, greater attention may be required for wound care, and future research could explore targeted adjunctive interventions. REGISTRATION: The meta-analysis protocol is registered with PROSPERO under registration number CD420251250487, Registered 11/01/2026. the implementation follows the registered protocol.