Summary:
In patients with complex diabetic foot ulcers (DFUs) involving exposed bone, tendon, muscle, and/or joint capsule with controlled osteomyelitis, adjunctive cryopreserved ultra-thick human amniotic membrane derived from umbilical cord (cUC) demonstrated comparable healing rates to standard of care (SOC) alone, which included debridement, wound management, offloading, and systemic antibiotics, though it was associated with similar adverse event rates.
| PICO | Description |
|---|---|
| Population | Adults with complex diabetic foot ulcers (DFUs) exhibiting exposed bone, tendon, muscle, and/or joint capsule, with controlled osteomyelitis. |
| Intervention | Adjunctive treatment with cryopreserved ultra-thick human amniotic membrane derived from umbilical cord (cUC), applied at baseline and reapplied every ≥4 weeks if healing stalled, for up to 4 applications. |
| Comparison | Standard of care (SOC) alone: surgical debridement, bone resection as needed, appropriate wound dressings, offloading strategies, and a 6-week course of systemic antibiotics. |
| Outcome | Complete healing at 26 weeks occurred in 66.1% (cUC + SOC) vs. 59.8% (SOC alone) (p = 0.40); at 50 weeks, healing rates were 77.1% vs. 71.6% (p = 0.29). Adverse event rates were comparable (89.8% vs. 87.3%). Though not statistically significant, cUC showed a trend toward higher long-term healing with fewer applications. |
Clinical Context
Diabetic foot ulcers (DFUs) remain one of the most devastating complications of diabetes, affecting approximately 15-25% of diabetic patients during their lifetime. Complex DFUs—those involving exposed bone, tendon, muscle, or joint capsule—present particular challenges, with healing rates far below simpler wounds and amputation risk substantially elevated. These wounds often fail to respond to standard care alone, creating urgent need for advanced wound therapies.
Human amniotic membrane has emerged as a promising biological wound covering, containing growth factors, cytokines, and extracellular matrix components that promote tissue regeneration. The amnion provides a scaffold for cell migration, delivers anti-inflammatory and antimicrobial properties, and does not elicit immune rejection. Cryopreservation allows storage and on-demand availability while maintaining biological activity.
Ultra-thick amniotic membrane derived from umbilical cord (cUC) represents an advancement over standard amnion preparations, with greater tissue thickness potentially providing enhanced growth factor delivery and longer-lasting wound coverage. This trial evaluated cUC in the most challenging DFU category—complex wounds with controlled osteomyelitis—where few therapeutic options exist.
Clinical Pearls
1. No Statistically Significant Benefit Over SOC: While cUC showed numerically higher healing rates (66.1% vs 59.8% at 26 weeks), the difference was not statistically significant (p=0.40). This highlights that in well-managed complex DFUs, excellent standard care may be equally effective as adding advanced biologics.
2. Controlled Osteomyelitis Doesn’t Preclude Healing: Both groups achieved substantial healing rates despite the presence of controlled osteomyelitis, demonstrating that aggressive wound management with appropriate infection control enables healing even in this challenging population.
3. Fewer Applications May Achieve Similar Results: The cUC protocol used fewer total applications compared to some other advanced wound therapies, yet achieved comparable outcomes. This has practical implications for treatment burden and cost considerations.
4. Safety Profile Comparable: Adverse event rates were similar between groups (89.8% vs 87.3%), indicating cUC doesn’t add significant safety concerns beyond those inherent in managing complex DFUs.
Practical Application
This trial’s results suggest that while cUC is safe and may offer modest benefit trends, it should not be considered first-line for all complex DFUs. Reserve advanced biologics for wounds clearly failing adequate standard care. The excellent healing rates in the SOC arm (59.8% at 26 weeks) reinforce that meticulous standard wound care—debridement, offloading, infection control, appropriate dressings—remains the foundation of DFU management.
When considering cUC, ensure standard care has been optimized first: adequate vascular perfusion, appropriate offloading device, infection controlled, and regular sharp debridement. Cost-benefit discussions with patients should acknowledge the lack of statistical superiority over SOC in this trial.
For patients with complex DFUs and controlled osteomyelitis, this study provides reassurance that aggressive wound care can achieve healing in the majority—a hopeful message for patients facing potential amputation.
Broader Evidence Context
Previous studies of amniotic membrane in simpler DFUs showed more robust benefit over standard care. The attenuated benefit in this trial may reflect the complexity of wounds studied or the high quality of SOC provided. Guidelines recommend considering advanced biologics when standard care fails, but this trial suggests the threshold for failure should be clearly defined.
Cost-effectiveness analyses of advanced wound therapies typically assume superiority over SOC; neutral results like these complicate reimbursement and utilization decisions.
Study Limitations
The trial may have been underpowered to detect a modest but clinically meaningful difference. Definition of “controlled osteomyelitis” varied across sites. The high healing rate in the SOC arm suggests enrolled centers had exceptional wound care expertise, which may not be generalizable to all practice settings.
Bottom Line
Cryopreserved ultra-thick amniotic membrane (cUC) did not significantly improve healing rates over standard of care in complex diabetic foot ulcers with controlled osteomyelitis, though numerical trends favored cUC. Both groups achieved substantial healing (~60-77%), emphasizing that excellent standard care remains the cornerstone of complex DFU management.
Source: Caporusso J, et al. “A Multi-Centre, Randomised, Controlled Clinical Trial Assessing Cryopreserved Ultra-Thick Human Amniotic Membrane in the Treatment of Complex Diabetic Foot Ulcers.” 2025. Read article
