Medical Journal of the Islamic Republic Of Iran

en Graphene Oxide and Reduced Graphene Oxide for Diabetic Wound Healing in Animal Models: A Systematic Review of Preclinical Evidence Endocrinology Endocrinology Systematic Review Background: Diabetic wounds result in significant morbidity, and current treatment options frequently yield incomplete healing. Graphene-derived nanomaterials, including GO and rGO, possess multifunctional properties that may facilitate tissue repair. This systematic review assessed animal evidence regarding their therapeutic effects and reported safety.    Methods: Following PRISMA 2020 guidelines, PubMed, Web of Science, and Scopus were searched up to March 15, 2025, for animal studies involving graphene-derived nanomaterials in diabetic full-thickness wounds. Study characteristics, outcomes, mechanisms, and safety findings were extracted. The risk of bias was assessed using SYRCLE. Due to heterogeneity, the synthesis was narrative.    Results: Twenty-three rodent studies met the inclusion criteria. GO and rGO were mainly incorporated into hydrogels, while fewer studies used scaffolds, microneedles, suspensions, or injections. Compared with untreated, vehicle, material-only, or standard-care controls, graphene-based treatments were generally associated with accelerated closure and more favorable repair markers, including collagen deposition, re-epithelialization, VEGF/CD31 expression, and reduced levels of IL-6, TNF-α, or NLRP3. Functionalized systems predominantly combined graphene with antibacterial, photothermal, nitric oxide-releasing, metal-ion, or bioactive components. SYRCLE assessment indicated a predominantly unclear risk of bias, primarily due to limited reporting of allocation concealment, random housing, and blinded outcome assessment. No significant local or systemic toxicity was reported during the short follow-up, although safety evaluation was limited.    Conclusion: Graphene-derived nanomaterials appear promising for diabetic wound repair in preclinical models. However, the evidence is limited by small-animal studies, short follow-up periods, heterogeneous formulations, and incomplete long-term biodistribution and safety assessments. Standardized preclinical studies, dose-response evaluations, and clinical trials are necessary prior to translation.   Animal models, Diabetic wounds, Graphene oxide, Reduced graphene oxide, Hydrogels, Nanomaterials, Wound healing 948 969 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-8751-4&slc_lang=en&sid=1 Roya Ghafoury royaghafoury@gmail.com 2003194753284600100809 2003194753284600100809 No Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Afsoon Mahmoodpour dr.afsoonmahmoodpour@gmail.com 2003194753284600100810 2003194753284600100810 No Endocrine Research Center, Institute of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Nahid Hashemi-madani nahid.hashemimadani@gmail.com 2003194753284600100811 2003194753284600100811 No Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Zahra Emami emami.z@iums.ac.ir 2003194753284600100812 2003194753284600100812 Yes Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran Manizhe Ataee Kachuee manizhe.ataei64@gmail.com 2003194753284600100813 2003194753284600100813 No Department of Radiology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran Mohammad E. Khamseh khamseh.m@iums.ac.ir 2003194753284600100814 2003194753284600100814 No Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran