{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:31:04Z","timestamp":1777948264649,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004513","name":"Harry Crossley Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004513","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Topically applied autologous blood clot therapy (TABCT) is a low\u2010cost regenerative modality proposed for complex wounds, yet its biological mechanism of action remains poorly defined. We investigated whether factors released from autologous blood clots promote peripheral blood mononuclear cell (PBMC) chemotaxis and fibroblast migration, and whether these effects are altered in individuals with metabolic syndrome\/type 2 diabetes (MetS\/DM). Twenty\u2010two participants (controls\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912; MetS\/DM\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) were recruited. Autologous clots were generated ex\u00a0vivo, cultured for 24\u2009h, and the secretome analysed for total protein, PDGF\u2010BB, P\u2010selectin and CCL\u20105. PBMC basal activation (ROS production, phagocytosis, migration, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    flux) was assessed, followed by live\u2010cell chemotaxis assays. Human dermal fibroblast migration was evaluated using a scratch assay. MetS\/DM\u2010derived PBMCs demonstrated heightened basal activation, including increased ROS production, migration velocity and sustained intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    flux. Clots from MetS\/DM participants released less total protein but significantly higher P\u2010selectin levels, consistent with platelet hyperactivation. Despite containing measurable growth factors, clot\u2010derived secretomes did not significantly enhance PBMC migration velocity or distance travelled, although directionality modestly increased. Similarly, secretome exposure failed to stimulate fibroblast\u2010mediated wound closure (&lt;\u200930% closure across groups). Pretreatment of blood with metformin, prednisone or amoxicillin had negligible effects on secretome composition or functional outcomes. These findings demonstrate that while TABCT\u2010derived secretomes exhibit chemotactic properties, they do not substantially promote immune cell recruitment or fibroblast migration in\u00a0vitro. The clinical benefits of TABCT may therefore be attributable primarily to its fibrin scaffold properties rather than bioactive factor release. Further mechanistic and translational studies are warranted.\n                  <\/jats:p>","DOI":"10.1111\/wrr.70153","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:31Z","timestamp":1774843951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autologous Blood Clot Therapy for Wounds: Investigating the Chemotactic Effect on\n                    <scp>PBMCs<\/scp>\n                    and Fibroblasts in Diabetes"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-5058","authenticated-orcid":false,"given":"Kayla","family":"Howard","sequence":"first","affiliation":[{"name":"Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine &amp; Health Sciences, Stellenbosch University  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Dhanraj","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine &amp; Health Sciences, Stellenbosch University  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-5019","authenticated-orcid":false,"given":"Kayleigh","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine &amp; Health Sciences, Stellenbosch University  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-2939","authenticated-orcid":false,"given":"Mari","family":"van de Vyver","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research Group, Department of Medicine, Faculty of Medicine &amp; Health Sciences, Stellenbosch University  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509359125"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2022.01.006"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1698674"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1657928"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.25270\/wnds\/22011"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2009.03.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002198\u20108"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom16020335"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2016.25.11.680"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2025.07.050"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.25270\/wnds\/22061"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.7547\/20\u2010140"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1479164113500680"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201022\u20100271"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imj.2025.100211"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2015.0635"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.791899"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.70155"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.7196\/SAMJ.2022.v112i10.16527"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010018\u20100783\u2010z"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1072288"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010025\u201006429\u2010z"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08\u20101308"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2013.37.6.423"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/2632010X231205366"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9030236"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050813"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111779"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186559"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1272809"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13112694"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/CWCMR.S189836"},{"issue":"9","key":"e_1_2_12_34_1","first-page":"317","article-title":"Efficacy and Safety of a Novel Autologous Wound Matrix in the Management of Complicated, Chronic Wounds: A Pilot Study","volume":"28","author":"Kushnir I.","year":"2016","journal-title":"Wounds"},{"issue":"7","key":"e_1_2_12_35_1","first-page":"84","article-title":"Safety and Efficacy of an Autologous Blood Clot Product in the Management of Texas 1A or 2A Neuropathic Diabetic Foot Ulcers: A Prospective, Multicenter, Open Label Pilot Study","volume":"30","author":"Snyder R. 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