Transfection of Hypoxia-Inducible Factor-1α in Wound Healing: A Systematic Review
In brief
HIF-1α gene delivery triples angiogenesis and shrinks wound area in mice
In seven pre-clinical studies, local application of HIF-1α increased angiogenesis-related gene expression two- to three-fold, boosted circulating angiogenic cells ten-fold, and reduced wound size compared with controls. Treated wounds showed more mature vessels and less necrosis, but the evidence is limited to normal and diabetic mouse models, so human safety and efficacy remain untested.
- Journal
- The Journal of surgical research (Q1)
- Published
- 17 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Mirza Farhana Iqbal Chowdhury, Amid Yazdani, Anum Iqbal, Afroza Rahman, Tanzeela Sameen Saeed, Muhammad Ramish Saeed, et al.
- PMID
- 42753360
- DOI
- 10.1016/j.jss.2026.08.018
Why clinicians should know about it
- Picked for Histology (top studies of the week, 20 September 2026): HIF‑1α transfection for wound healing
- Picked for Surgical Oncology (top studies of the week, 20 September 2026): HIF‑1α transfection wound healing systematic review
Abstract
INTRODUCTION: Hypoxia-inducible factor-1α (HIF-1α) has emerged as a promising target for enhancing wound healing. Here, we conducted a systematic review to evaluate the efficacy of HIF-1α in improving wound healing. METHODS: We included the latest randomized controlled trials, quasi-experimental studies, nonrandomized trials, controlled before-after studies, analytical studies (cohort study, case-control study), and comparative cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. We searched the databases, including PubMed, the Cochrane Library (Cochrane Central Register of Controlled Trials-CENTRAL), EMBASE, and Scopus, until March 15, 2025. Seven studies reporting accelerated healing via the local application of HIF-1α in normal and diabetic mice were included. RESULTS: A two- to three-fold increase in the expression of angiogenesis-related genes (vascular endothelial growth factor, Acta2, and Pecam1) and a 10-fold increase in circulating angiogenic cells were observed in the treated wounds. Vessel maturity in HIF-1α treated wounds increased compared with control, across the included studies. Statistical significance was set at P < 0.05 for angiogenesis and vessel maturity. Significant upregulation of HIF-1α, vascular endothelial growth factor, placental growth factor, and platelet-derived growth factor-B messenger RNA levels was observed (P < 0.05). Histological evidence of increased neovascularization with increased endothelial and smooth muscle cell densities compared to the control groups was observed. Combination therapy with HIF-1α plasmid significantly reduced the wound area (P < 0.05). Angiogenesis, tissue perfusion, and cell homing were three times higher in wounds with HIF-1α transfection. HIF-1α-treated flaps showed significantly less necrosis (P < 0.05) than those in the control group. CONCLUSIONS: HIF-1α-treated wounds showed increased wound healing along with improved neovascularization, vessel maturity, tissue perfusion, and cell homing. We suggest that future studies are warranted on HIF-1α's efficacy and safety in clinical trials in revolutionizing the wound healing arena.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.