Diabetic foot ulcers (DFUs) affect approximately 15–25% of people with diabetes over their lifetime and remain a leading cause of non-traumatic lower-limb amputation worldwide. Standard wound care — debridement, offloading, infection control, and moist wound management — achieves healing in many cases, but a significant proportion of DFUs remain chronic and difficult to close. Over the past decade, an expanding body of peer-reviewed research has examined biologic and growth factor therapies as adjuncts to standard care, aiming to stimulate the cellular and molecular processes that drive tissue repair. This post reviews the current clinical evidence for three main categories of these treatments: platelet-rich plasma, recombinant growth factors, and stem cell therapies.
Platelet-Rich Plasma: Building the Evidence Base
Platelet-rich plasma (PRP) is an autologous blood product prepared by centrifuging a patient’s own blood to concentrate platelets and their associated growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and epidermal growth factor (EGF). These mediators play central roles in angiogenesis, fibroblast recruitment, collagen synthesis, and re-epithelialization — processes that are dysregulated in chronic diabetic wounds.
A 2023 systematic review published in Frontiers in Endocrinology analyzed 15 randomized controlled trials (RCTs) involving over 1,000 patients with DFUs and found that PRP significantly improved complete wound healing rates compared to conventional care (Zhao et al., 2023). A concurrent systematic review and meta-analysis in the Journal of Orthopaedic Surgery and Research, covering 1,559 patients across multiple RCTs, reported that PRP reduced time to complete healing and increased the likelihood of full wound closure (Chen et al., 2023). The safety profile was favorable — PRP did not increase wound complications or recurrence rates compared to standard treatment. A 2025 meta-analysis in Acta Diabetologica corroborated these findings, estimating approximately 3.7-fold higher odds of complete healing in the PRP group versus conventional care (Moura et al., 2025).
Despite these encouraging results, variability in PRP preparation protocols, platelet concentration thresholds, and application frequency limits direct comparisons across studies. Larger, standardized RCTs are needed to establish optimal treatment parameters.
Recombinant Growth Factors: From Becaplermin to Novel Agents
The concept of delivering specific growth factors topically to chronic wounds has been pursued since the 1990s. Becaplermin (recombinant human PDGF-BB) remains the only growth factor therapy approved by the U.S. FDA for DFUs, and clinical trials established that it significantly increases the incidence of complete wound closure compared to placebo gel when used alongside good wound care. However, its adoption has been tempered by concerns about a potential association with increased cancer risk at high cumulative doses, though subsequent analyses have not confirmed a clear causal relationship.
A comprehensive systematic review in Advances in Wound Care (2022) examined 41 clinical trials across a range of topical biologic agents — including fibroblast growth factors (FGFs), epidermal growth factor, and human amnion/chorion allografts — in chronic diabetic wounds (Lev-Tov et al., 2022). The review found that dehydrated human amnion and chorion allograft (dHACA) and hypothermically stored amniotic membrane products consistently increased rates of complete ulcer healing and reduced wound size compared to standard care. FGF-1, while showing a modest benefit in some studies, demonstrated inconsistent results. These findings highlight that the clinical impact of growth factor therapies varies considerably by agent and formulation.
Stem Cell Therapies: Promising Early Data
Stem cell-based approaches represent the frontier of regenerative medicine for DFUs. Mesenchymal stem cells (MSCs) — derived from bone marrow, adipose tissue, umbilical cord, or placenta — exert wound-healing effects through paracrine signaling, secreting a range of cytokines and growth factors that promote angiogenesis, reduce inflammation, enhance extracellular matrix remodeling, and recruit local repair cells.
A 2022 review in Cells summarized preclinical and early clinical evidence, concluding that both autologous and allogeneic MSCs appear safe and show measurable improvements in wound closure and perfusion in DFU patients, with emerging signals of reduced amputation risk (Gao et al., 2022). A 2025 systematic review and meta-analysis in BMC Medicine found that stem cells from multiple tissue sources promoted wound healing in DFUs, though variability in stem cell origin, administration route, and co-interventions made cross-study comparisons challenging (Liu et al., 2025). Bone marrow-derived and adipose-derived MSCs showed the most consistent benefit in included trials. Larger, phase III RCTs are now underway to better define efficacy, safety, and optimal delivery methods.
Key Clinical Takeaways
The evidence supports biologic and growth factor therapies as adjuncts — not replacements — for comprehensive diabetic foot wound care, which continues to rely on thorough debridement, pressure offloading, glycemic optimization, vascular assessment, and infection management. Autologous PRP has the most consistent RCT evidence for improving complete healing rates in DFUs without increasing harm. Recombinant growth factors like becaplermin remain FDA-approved adjuncts with established efficacy; amniotic membrane products also demonstrate meaningful wound closure benefits. Stem cell therapies hold substantial promise, particularly for patients with concurrent peripheral arterial disease and impaired tissue perfusion, though evidence from large, well-controlled trials is still maturing.
As this field evolves, clinicians managing DFUs benefit from remaining current with published systematic reviews and international guidelines to identify which patients are most likely to respond to these adjunctive therapies and to integrate them appropriately within a structured, multidisciplinary care framework.
References
- Zhao M, et al. Platelet-rich plasma for the treatment of diabetic foot ulcer: a systematic review. Frontiers in Endocrinology. 2023;14:1256081.
- Chen H, et al. Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcer healing: a systematic review and meta-analysis of randomized controlled trials. Journal of Orthopaedic Surgery and Research. 2023;18(1):394.
- Moura J, et al. Efficacy and safety of platelet-rich plasma versus conventional care in diabetic foot ulcers: a meta-analysis of randomized controlled trials. Acta Diabetologica. 2025.
- Lev-Tov H, et al. Topical biological agents as adjuncts to improve wound healing in chronic diabetic wounds: a systematic review of clinical evidence and future directions. Advances in Wound Care. 2022;11(9):474–494.
- Gao F, et al. Stem cell-based therapeutic strategies in diabetic wound healing. Cells. 2022;11(19):2979.
- Liu Y, et al. Impacts of stem cells from different sources on wound healing rate in diabetic foot ulcers: a systematic review and meta-analysis. BMC Medicine. 2025;23(1):76.
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