Cellular, Acellular, and Matrix‐Like Placental Products for Diabetic Foot Ulcers: A 12‐Week Randomised‐Trial Meta‐Analysis

ABSTRACT

Placental‐derived cellular, acellular, and matrix‐like products (CAMPs) are widely used as adjuncts to standard care for diabetic foot ulcers (DFUs), but trials differ in product class, comparator, and healing window. We estimated the effect of adjunctive placental‐derived CAMPs on complete wound closure at a single, clinically meaningful 12‐week endpoint. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261399700) and reported per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020, with search reporting guided by PRISMA‐S. PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched through 21 June 2026 for randomised or quasi‐randomised trials comparing a placental, amniotic, chorionic, amnion‐chorion, placental membrane, or umbilical cord‐derived product plus standard care against standard care or a non‐placental control in adults with active DFUs. The primary outcome was complete wound closure at 12 weeks. Risk ratios (RRs) were pooled in a random‐effects model (inverse‐variance, restricted maximum likelihood [REML], Hartung‐Knapp). Risk of bias was assessed with the Cochrane Risk of Bias 2 tool (RoB 2) for the 12‐week outcome and certainty with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Prespecified sensitivity analyses included odds ratios, leave‐one‐out, product‐class subgroups, and exclusion of high‐risk‐of‐bias studies. Of 474 records, 14 randomised articles were retained; 9 standard‐care‐controlled comparisons (944 participants) provided extractable 12‐week complete‐closure data for the primary analysis. Complete closure occurred in 298 of 505 product‐treated participants (59.0%) versus 157 of 439 controls (35.8%). Adjunctive CAMPs increased the likelihood of closure (RR 1.70, 95% confidence interval [CI] 1.31–2.20). Heterogeneity was moderate (I ²  = 51.9%) and the prediction interval crossed the null (0.93–3.11). The effect was robust to leave‐one‐out analysis (RR 1.59–1.81), an odds‐ratio model (odds ratio [OR] 3.36, 95% CI 1.68–6.71), and exclusion of the single high‐risk‐of‐bias trial (RR 1.73, 95% CI 1.29–2.33). Certainty was moderate, downgraded once for inconsistency. Adjunctive placental‐derived CAMPs improve 12‐week complete closure of DFUs compared with standard care, with moderate certainty. The wide prediction interval indicates that the average benefit may not be reproduced by every product, population, or setting, underscoring the need for product‐specific, standard‐care‐anchored trials and for coverage policy grounded in endpoint‐specific randomised evidence.

Trial Registration: Registration number: CRD420261399700.