Clinical trials on 3D bioprinted scaffolds for lower extremity vascular, diabetic and pressure ulcers: a systematic review

Abstract

Aim 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. Methods 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, in vitro, 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. Results 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, >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). Conclusion 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.