Stem Cells, Exosomes, and Biologics: Do They Work in Wound Care?

Discover how stem cells, exosomes, and biologics support chronic wound healing. Learn benefits, evidence, and best practices in modern wound care.

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10/20/20257 min read

Restorigin™ amniotic membrane applied to a leg ulcer

Advanced biologic therapies — including stem cells, exosomes (extracellular vesicles), and other biologics such as growth factors and skin substitutes — have generated real excitement in wound care. For clinicians and patients dealing with chronic wounds (diabetic foot ulcers, venous leg ulcers, pressure injuries), these products promise to move a stalled wound toward closure by improving cell signaling, reducing inflammation, promoting blood vessel growth, or providing a temporary skin matrix. At the same time, evidence varies by product class, condition, and study quality. This guide explains the current evidence, practical uses, safety and cost considerations, and how these options fit into standard wound-care pathways.

Short summary: Some biologics show promise. Skin substitutes and select growth-factor products have RCT evidence for specific indications; stem cell and exosome therapies show encouraging early data (preclinical and small clinical studies), but larger, higher-quality trials and standardization are still needed.

What we mean by “stem cells,” “exosomes,” and “biologics”

Stem cell therapies in wound care typically use mesenchymal stem/stromal cells (MSCs) or other progenitor cells derived from bone marrow, adipose tissue, umbilical cord, or skin. MSCs may be applied directly (injected or placed in a matrix) or used to seed grafts. They are thought to act largely through paracrine signaling (releasing cytokines and growth factors).
Exosomes (a form of extracellular vesicle, EV) are tiny, cell-derived particles containing proteins, RNAs and lipids. They’re increasingly studied as a cell-free way to deliver the beneficial signaling effects of stem cells without transplanting live cells. Preclinical models show exosomes promote angiogenesis, re-epithelialization, and collagen remodeling.
Biologics is a broad term that includes living skin substitutes (e.g., bilayered cell-based products), acellular matrices, recombinant growth factors (e.g., PDGF/becaplermin), and platelet-rich plasma (PRP). These products act by replacing or enhancing the wound environment to support healing. Some biologics are FDA-cleared for specific wound types.

What does the evidence say (by product class)?

Skin substitutes and cellular/tissue-based products

There is moderate-quality clinical evidence that certain skin substitutes can improve healing rates for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) when used in addition to standard care (debridement, offloading, compression as appropriate). Health-technology assessments and randomized trials have shown improved closure rates for several products, although results vary by product and ulcer type. Insurance coverage decisions (e.g., Medicare Local Coverage Determinations) reflect selective evidence-based use. Clinicians should follow product instructions and use skin substitutes as part of a comprehensive wound-care plan.

Recombinant growth factors

Topical recombinant PDGF (becaplermin) has RCT evidence demonstrating improved healing in some DFUs, and it remains an option for selected, non-healing neuropathic ulcers. However, clinicians weigh benefits against cost and contextual factors (eg, infection control, offloading). Recent guidance and reviews place growth factors as adjunctive treatments in appropriate cases.

Platelet-rich plasma (PRP)

Systematic reviews and meta-analyses indicate that autologous PRP (injected or topically applied) can improve healing rates for DFUs versus standard care in several trials, though heterogeneity in PRP preparation and application makes broad conclusions difficult. PRP is used as a biostimulatory adjunct when other measures alone are insufficient.

Mesenchymal stem cells (MSCs) and cell therapies

Preclinical studies and small clinical trials suggest MSCs (bone marrow–, adipose-, or umbilical-derived) may accelerate wound closure via anti-inflammatory and pro-angiogenic actions. Recent systematic reviews of stem cell therapy in chronic wounds summarize encouraging signals for safety and potential benefit, but they also note that study sizes are small, methods vary, and long-term data are limited. Consistency of cell source, dose, delivery method, and regulatory oversight are key issues that remain to be standardized.

Exosomes and other extracellular vesicles (EVs)

Exosomes are an active area of research. Animal and early human studies show exosome-based approaches promote angiogenesis, re-epithelialization, and collagen deposition, which may help chronic wounds heal. Reviews in the last few years highlight exosomes’ potential as a cell-free biologic with lower immunogenicity risk than cell transplants. However, clinical trials are early-stage, and manufacturing/characterization standards for EV products still need broad consensus.

How strong is the evidence overall?

In short: varies by product.

For skin substitutes and some growth-factor products, there is randomized controlled-trial evidence of benefit in selected ulcer types (DFU, VLU), and health-technology assessments back their conditional use.
For PRP, the evidence is growing; meta-analyses show pooled benefits for DFUs but heterogeneity and variable product preparation reduce certainty.
For stem cells and exosomes, data are mostly preclinical and early-phase clinical. Systematic reviews report promising signals, but results are preliminary and more rigorous, larger randomized trials are needed before routine adoption.

A recent network meta-analysis comparing many advanced therapies suggests that no single biologic is a universal winner for every ulcer type. The best choice depends on the wound etiology, patient factors, and the local evidence for each product.

Why these products might help

Skin substitutes provide a scaffold and living cells to jump-start granulation and epithelial migration.
Growth factors (like PDGF) supply specific signaling to recruit fibroblasts and endothelial cells.
PRP concentrates autologous growth factors to stimulate cell proliferation.
MSCs can modulate inflammation, release pro-healing cytokines, and support angiogenesis.
Exosomes carry microRNA, proteins, and lipids that alter gene expression and cell behavior in the wound bed.

Understanding mechanisms helps clinicians combine biologics with wound-bed preparation (debridement, infection control, moisture balance, offloading) so the product acts on a receptive wound.

Practical clinical considerations

Match the therapy to the wound and patient. Skin substitutes or PDGF are options for chronic DFUs or VLUs refractory to standard care. MSC or exosome therapies are promising but, in many settings, still investigational.
Do not skip basics. Biologics rarely replace the need for debridement, infection control, offloading (for DFUs), compression (for VLUs), or optimization of nutrition and perfusion. They are adjuncts.
Consider cost and coverage. Many biologics are expensive; reimbursement varies. Clinicians should document prior conservative care and follow payer criteria for advanced products (for example, Medicare local coverage for some cellular/tissue-based products).
Safety and regulation. Cell therapies and exosome products have different regulatory statuses across jurisdictions. Safety signals in trials have been acceptable so far, but long-term monitoring and standardized manufacturing are critical. Use regulated products and follow trial/registry data when available.
Quality of evidence. Evaluate the strength of evidence: RCTs and meta-analyses (for skin substitutes, PDGF, PRP) are stronger than small single-site cell therapy studies. For stem cells and exosomes, look for randomized, well-powered trials before assuming clinical benefit.

Real-world examples and standard indications

Apligraf® and other living skin substitutes have demonstrated benefits in some DFU and VLU RCTs and are widely used under specific protocols. Use as adjunctive therapy after debridement and with concurrent standard care.
Becaplermin (rhPDGF-BB) may be considered for recalcitrant neuropathic DFUs with adequate blood supply as a topical adjunct. Cost and patient selection matter.
PRP is commonly used in specialized clinics for DFUs and chronic wounds; look for standardized PRP preparation protocols and controlled data.
MSC and exosome investigational therapies: promising early results but generally recommended within clinical trials or registries until larger confirmatory studies are available.

Future directions

The next few years will likely bring:

Larger, better-designed RCTs for MSCs and exosomes.
Standardized manufacturing and potency assays for cell and EV products.
Head-to-head comparisons and health-economic analyses that clarify which biologics are cost-effective for which wounds.
Combined approaches (eg, exosome-loaded matrices or MSC-seeded grafts) designed to exploit complementary mechanisms.

Bottom line: where biologics fit in wound care today

Use biologics selectively and thoughtfully. For some chronic DFUs and VLUs, skin substitutes and selected growth-factor products have an evidence base and defined indications. PRP has supportive data but variable preparation standards.
Treat stem cells and exosomes as promising but still emerging. They offer biologically plausible mechanisms and encouraging early results, but broader clinical adoption requires larger, standardized trials and reproducible manufacturing. Until then, consider these options within trials or when institutional pathways allow.
Always pair biologics with sound wound-care fundamentals: debridement, infection control, offloading/pressure redistribution, vascular assessment, and optimization of nutrition and glycemic control. Biologics can be the “accelerant,” but they rarely replace fundamentals.

More Information

For more information on the latest effective wound care, contact us to set up a time for a call.

Sources

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* This blog is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment.

Restorigin™ amniotic membrane on a leg ulcer