{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T12:18:24Z","timestamp":1769257104477,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes\u2014including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality\u2014were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 \u00b1 12 years; diabetes duration 18 \u00b1 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p &lt; 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-\u03b1). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies.<\/jats:p>","DOI":"10.3390\/cells14151196","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T10:48:08Z","timestamp":1754304488000},"page":"1196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microvascular, Biochemical, and Clinical Impact of Hyperbaric Oxygen Therapy in Recalcitrant Diabetic Foot Ulcers"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-9948","authenticated-orcid":false,"given":"Daniela","family":"Martins-Mendes","sequence":"first","affiliation":[{"name":"RISE-Health, School of Medicine and Biomedical Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Avenida Fernando Pessoa 150, 4420-096 Gondomar, Portugal"},{"name":"CECLIN\u2014Centre of Clinical Studies, Hospital Fernando Pessoa, Avenida Fernando Pessoa 150 S\u00e3o Cosme, 4420-096 Gondomar, Portugal"},{"name":"Fernando Pessoa-Biomedical Health Sciences (FPBHS), FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, University Fernando Pessoa, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"},{"name":"Bomedicine Department, Faculty of Medicine, University of Porto, Alameda Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-4565","authenticated-orcid":false,"given":"Raquel","family":"Costa","sequence":"additional","affiliation":[{"name":"Centro de Biotecnologia e Qu\u00edmica Fina Laborat\u00f3rio Associado, Escola superior de Biotecnologia, Universidade Cat\u00f3lica Portuguesa, R. de Diogo Botelho 1327, 4169-005 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-7670","authenticated-orcid":false,"given":"Ilda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Bomedicine Department, Faculty of Medicine, University of Porto, Alameda Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]},{"given":"\u00d3scar","family":"Camacho","sequence":"additional","affiliation":[{"name":"Hyperbaric Medical Unit, Unidade Local de Sa\u00fade de Matosinhos, E. P. E (Entidade P\u00fablica Empresarial), R. de Dr. Eduardo Torres, 4464-513 Senhora da Hora, Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazer, R. de Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-5450","authenticated-orcid":false,"given":"Pedro Barata","family":"Coelho","sequence":"additional","affiliation":[{"name":"RISE-Health, School of Medicine and Biomedical Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Avenida Fernando Pessoa 150, 4420-096 Gondomar, Portugal"},{"name":"CECLIN\u2014Centre of Clinical Studies, Hospital Fernando Pessoa, Avenida Fernando Pessoa 150 S\u00e3o Cosme, 4420-096 Gondomar, Portugal"},{"name":"Fernando Pessoa-Biomedical Health Sciences (FPBHS), FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, University Fernando Pessoa, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"},{"name":"Hospital de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal"}]},{"given":"V\u00edtor","family":"Paix\u00e3o-Dias","sequence":"additional","affiliation":[{"name":"Internal Medicine Department\u2014Centro Hospitalar de Vila Nova de Gaia\/Espinho EPE, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"Carla","family":"Lu\u00eds","sequence":"additional","affiliation":[{"name":"RISE-Health, School of Medicine and Biomedical Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Avenida Fernando Pessoa 150, 4420-096 Gondomar, Portugal"},{"name":"CECLIN\u2014Centre of Clinical Studies, Hospital Fernando Pessoa, Avenida Fernando Pessoa 150 S\u00e3o Cosme, 4420-096 Gondomar, Portugal"},{"name":"Fernando Pessoa-Biomedical Health Sciences (FPBHS), FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, University Fernando Pessoa, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"},{"name":"Bomedicine Department, Faculty of Medicine, University of Porto, Alameda Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-8255","authenticated-orcid":false,"given":"Ana Cl\u00e1udia","family":"Pereira","sequence":"additional","affiliation":[{"name":"RISE-Health, School of Medicine and Biomedical Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Avenida Fernando Pessoa 150, 4420-096 Gondomar, Portugal"},{"name":"CECLIN\u2014Centre of Clinical Studies, Hospital Fernando Pessoa, Avenida Fernando Pessoa 150 S\u00e3o Cosme, 4420-096 Gondomar, Portugal"},{"name":"Fernando Pessoa-Biomedical Health Sciences (FPBHS), FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, University Fernando Pessoa, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3984","authenticated-orcid":false,"given":"R\u00faben","family":"Fernandes","sequence":"additional","affiliation":[{"name":"RISE-Health, School of Medicine and Biomedical Sciences, Fernando Pessoa University, Fernando Pessoa Teaching and Culture Foundation, Avenida Fernando Pessoa 150, 4420-096 Gondomar, Portugal"},{"name":"CECLIN\u2014Centre of Clinical Studies, Hospital Fernando Pessoa, Avenida Fernando Pessoa 150 S\u00e3o Cosme, 4420-096 Gondomar, Portugal"},{"name":"Fernando Pessoa-Biomedical Health Sciences (FPBHS), FP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, University Fernando Pessoa, Pra\u00e7a de 9 de Abril 349, 4249-004 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7780-0901","authenticated-orcid":false,"given":"Jorge","family":"Lima","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, 4200-465 Porto, Portugal"},{"name":"Pathology Department, Faculty of Medicine, University of Porto, Alameda Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-5541","authenticated-orcid":false,"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"Bomedicine Department, Faculty of Medicine, University of Porto, Alameda Prof Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2337\/diacare.27.5.1047","article-title":"Global prevalence of diabetes: Estimates for the 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