{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:03:58Z","timestamp":1790229838481,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Three-dimensional (3D) bioprinting enables fabrication of bioink-based scaffolds that mimic native tissue architecture. This systematic review aims to evaluate the safety profile and healing times of 3D-bioprinted scaffolds clinically tested in human lower limb ulcers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science were searched from January 2000 to June 2025. Inclusion criteria encompassed only clinical studies; animal,\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and non-clinical reports were excluded. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for randomized controlled trials and the Methodological Index for Non-Randomized Studies (MINORS) for non-randomized studies. Results were synthesized narratively due to clinical and methodological heterogeneity across studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 476 records screened, eight studies met the inclusion criteria: two randomized controlled trials and six single-arm studies. The combined sample size across all studies was 139 patients. Both RCTs reported a statistically significant reduction in time to complete epithelialization versus standard dressings. In the single-arm studies, &amp;gt;80% of ulcers achieved complete epithelialization within 12 weeks. No treatment-related serious adverse events were reported. Risk-of-bias assessments identified methodological limitations across studies (variable randomization and blinding, small sample sizes, and limited follow-up).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current clinical evidence indicates that 3D-bioprinted scaffolds, particularly Autologous Minimally Manipulated Homologous Adipose Tissue (AMHAT) and polylactic-acid gelatin constructs, represent a promising and apparently safe approach to accelerate ulcer healing and improve cosmetic outcomes. However, the number of patients included in each study were small with relatively short follow-up. Larger, high-quality randomized trials with longer follow-up are needed to confirm efficacy and long-term safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1912135","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:37:41Z","timestamp":1790228261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical trials on 3D bioprinted scaffolds for lower extremity vascular, diabetic and pressure ulcers: a systematic review"],"prefix":"10.3389","volume":"14","author":[{"given":"Lok Lam Lorraine","family":"Cheng","sequence":"first","affiliation":[{"name":"Division of Vascular & Endovascular Surgery, Department of Surgery, Queen Mary Hospital, University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Chit","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Vascular & Endovascular Surgery, Department of Surgery, Queen Mary Hospital, University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiu Che","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Vascular & Endovascular Surgery, Department of Surgery, Queen Mary Hospital, University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.3390\/polym16172456","article-title":"Application of 3D-Printed bioinks in chronic wound healing: a scoping review","volume":"16","author":"Abuhamad","year":"2024","journal-title":"Polymers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"464","DOI":"10.3390\/pharmaceutics14020464","article-title":"The 3D bioprinted scaffolds for wound healing","volume":"14","author":"Antezana","year":"2022","journal-title":"Pharmaceutics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e4588","DOI":"10.1097\/GOX.0000000000004588","article-title":"Autologous minimally manipulated homologous adipose tissue (AMHAT) for treatment of nonhealing diabetic foot ulcers","volume":"10","author":"Armstrong","year":"2022","journal-title":"Plast. 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