When Wounds Won't Heal: Understanding Diabetic Foot Ulcers and Vascular Solutions
Every year, more than 100,000 Americans with diabetes undergo lower extremity amputations. The pathway to amputation almost always begins the same way: with a foot ulcer that won't heal. These diabetic foot ulcers (DFUs) affect approximately 6.3 million people in the United States annually, and roughly 14-24% of diabetic patients will develop a foot ulcer at some point in their lives.
Here's the concerning progression: once a diabetic foot ulcer develops, approximately 20% will lead to amputation. And for those who undergo amputation, the five-year mortality rate approaches 50-70%—worse than most cancers. These statistics reveal that diabetic foot ulcers aren't just minor complications of diabetes. They're serious medical events that, when they fail to heal, set in motion a cascade with potentially catastrophic consequences.
Why Do Diabetic Foot Ulcers Form?
Diabetic foot ulcers result from a combination of three diabetes-related complications:
1. Neuropathy (nerve damage):
High blood glucose levels damage peripheral nerves, causing loss of protective sensation in the feet. Patients can't feel pressure points, minor injuries, or developing wounds. A pebble in the shoe, an ill-fitting boot, or repetitive pressure from walking creates tissue damage that goes unnoticed until an ulcer has formed.
Motor neuropathy also causes muscle imbalances, leading to foot deformities (hammertoes, Charcot foot) that create abnormal pressure distribution and increase ulcer risk.
2. Peripheral artery disease (impaired blood flow):
Diabetes accelerates atherosclerosis, causing narrowing or blockage of arteries supplying the legs and feet. This ischemia (inadequate blood flow) is critical because wound healing requires robust circulation to deliver oxygen, nutrients, immune cells, and growth factors to the injury site.
Diabetic patients develop particularly severe peripheral artery disease, often affecting smaller, more distal vessels that are difficult to treat with conventional revascularization.
3. Immune dysfunction:
Elevated glucose levels impair white blood cell function, reducing the body's ability to fight infection. Once bacteria colonize a diabetic foot ulcer, the impaired immune response allows infection to progress rapidly, sometimes to life-threatening depths (osteomyelitis—bone infection).
The convergence of these three factors—can't feel the injury forming, can't heal it once it occurs, can't fight infection when it develops—explains why diabetic foot ulcers are so dangerous.
Types of Diabetic Foot Ulcers: Neuropathic vs. Ischemic
Not all diabetic foot ulcers are the same. Understanding the dominant pathology helps determine treatment:
Neuropathic ulcers:
These occur at pressure points on the plantar (bottom) surface of the foot—under the metatarsal heads, heel, or tips of hammertoes. The ulcers are typically painless (due to neuropathy) with good blood flow (palpable pulses, normal ankle-brachial index).
The primary problem: repetitive mechanical trauma combined with loss of protective sensation. Treatment focuses on pressure offloading (special footwear, total contact casting), infection control, and wound care. With adequate offloading and good blood flow, these ulcers often heal.
Neuroischemic ulcers:
These combine neuropathy with significant peripheral artery disease. The ulcers may occur at pressure points but also at the margins of the foot, toes, or anywhere with borderline blood flow. Pulses are diminished or absent, and vascular testing confirms ischemia.
The primary problem: inadequate blood flow prevents healing. Even with perfect offloading and wound care, these ulcers won't heal unless circulation improves. This is where the treatment challenge becomes acute—and where regenerative medicine offers potential solutions.
Standard Treatment: The Foundation of Care
Evidence-based diabetic foot ulcer management includes multiple components:
Glycemic control: Optimizing blood glucose slows neuropathy progression and improves immune function, though it won't reverse existing nerve damage.
Pressure offloading: Removing mechanical stress from the wound is essential. Total contact casting, removable cast walkers, or specialized diabetic footwear redistribute pressure away from the ulcer.
Debridement: Removing dead tissue and callus edges promotes healing and allows assessment of wound depth.
Infection control: Appropriate antibiotics for infected ulcers, aggressive surgical debridement if osteomyelitis develops.
Advanced wound therapies: Negative pressure wound therapy, bioengineered skin substitutes, growth factor applications (becaplermin gel), hyperbaric oxygen therapy—all have evidence supporting their use in appropriate contexts.
Revascularization: For ischemic or neuroischemic ulcers, restoring blood flow through angioplasty, stenting, or bypass surgery is often essential for healing.
These interventions work well when blood flow is adequate or can be restored. But a significant subset of patients—those with unreconstructable vascular disease or failed revascularization—face chronic non-healing ulcers despite optimal standard care.
The Vascular Problem: When Blood Flow Can't Be Restored
Diabetic patients with peripheral artery disease often develop particularly challenging anatomy:
Diffuse disease affecting multiple arterial segments rather than focal blockages
Involvement of below-the-knee vessels and small pedal arteries that are difficult or impossible to bypass surgically
Heavy calcification that makes balloon angioplasty ineffective
Lack of suitable vein for bypass grafting (previous vein harvest for coronary bypass, or vein damage from diabetes)
When vascular surgeons determine that revascularization isn't technically feasible, these patients enter a difficult situation: their ulcer won't heal without improved blood flow, but traditional methods to restore flow aren't possible.
This is the population most at risk for amputation—and the population where angiogenic therapy offers the most compelling rationale.
Therapeutic Angiogenesis: Growing New Circulation
The biological premise behind angiogenic therapy for diabetic foot ulcers is straightforward: if the ulcer won't heal because blood flow is inadequate, and conventional revascularization can't restore flow, can we stimulate the body to grow entirely new blood vessels to supply the ischemic tissue?
Your body attempts this naturally through wound healing and collateral vessel formation. But in diabetic patients with severe PAD, this process is profoundly impaired:
High glucose levels interfere with VEGF signaling and endothelial cell function
Advanced glycation end-products (AGEs) accumulate in vessel walls, creating a hostile environment for new vessel growth
Diabetic patients have reduced numbers and impaired function of endothelial progenitor cells—the bone marrow-derived cells that normally participate in vessel formation
Chronic inflammation produces anti-angiogenic signals that block new vessel formation
Angiogenic cell therapy aims to overcome these deficits by delivering cells that produce high concentrations of growth factors, recruit additional progenitor cells, and create a more permissive environment for new blood vessel formation.
ACP-01 for Diabetic Foot Ulcers
Hemostemix's ACP-01 (Angiogenic Cell Precursors) has been studied in patients with chronic diabetic foot ulcers that failed to heal despite standard wound care and, where attempted, revascularization.
The treatment approach:
Patient's own blood is collected and processed to isolate cells with strong angiogenic potential (autologous therapy—no immune rejection risk).
Cells are expanded in the laboratory under conditions that enhance their ability to produce vascular growth factors.
Cells are delivered via intramuscular injection into the muscles of the affected foot and lower leg, targeting ischemic tissue around the non-healing ulcer.
The delivered cells release angiogenic signals (VEGF, FGF, HGF, and others) that stimulate formation of new capillary networks, improving blood flow to the wound bed and surrounding tissue.
Clinical Evidence and Wound Healing Outcomes
Investigational Studies of ACP-01 in diabetic patients with chronic wounds have shown:
Wound healing rates: Patients with chronic non-healing diabetic foot ulcers showed improvements in wound closure rates. Some wounds that had been present for months or even years achieved complete healing after ACP-01 treatment combined with standard wound care.
Tissue perfusion: Objective measurements (transcutaneous oxygen pressure, laser Doppler flowmetry) documented improvements in tissue oxygenation, confirming that new blood vessels had formed and were delivering oxygen to previously ischemic areas.
Limb salvage: In patients facing potential amputation due to non-healing ischemic ulcers, angiogenic therapy improved limb preservation rates.
Safety: The autologous nature of ACP-01 provides an excellent safety profile with no significant adverse events related to the cell therapy itself across hundreds of treated patients.
These findings align with broader research on cell-based therapies for diabetic foot ulcers and critical limb ischemia. Multiple trials have demonstrated that angiogenic cell therapy can improve wound healing in diabetic patients with vascular insufficiency who haven't responded to standard care.
Who Should Consider ACP-01 for Diabetic Foot Ulcers?
ACP-01 is being studied for diabetic patients with foot ulcers who:
Have chronic non-healing ulcers (typically present for 12+ weeks despite standard care)
Have evidence of peripheral artery disease or ischemia (neuroischemic ulcers)
Are not candidates for revascularization, or have failed previous revascularization attempts
Continue to have non-healing wounds despite optimal wound care, offloading, and infection control
The critical distinction: ACP-01 addresses the vascular component of diabetic foot ulcers. It's most appropriate for patients whose wounds won't heal because of inadequate blood flow. Purely neuropathic ulcers with excellent blood flow may not benefit from angiogenic therapy—those typically heal with proper offloading and wound care alone.
What Patients and Caregivers Should Know
If you have a diabetic foot ulcer that isn't healing despite weeks or months of standard treatment, understanding the vascular component is critical.
Key steps:
Get vascular assessment: Ask your wound care specialist or podiatrist: 'Is inadequate blood flow preventing my wound from healing?' Request vascular testing (ankle-brachial index, toe pressures, TcPO2) to objectively measure tissue perfusion.
Explore all revascularization options: If blood flow is the problem, traditional revascularization should be attempted when possible. Consult a vascular surgeon or interventional radiologist about whether your anatomy is suitable for angioplasty, stenting, or bypass.
Consider angiogenic therapy for no-option cases: If revascularization isn't possible or has failed, research clinical trials of ACP-01 and other angiogenic therapies at hemostemixclinicaltrials.com.
Maintain comprehensive wound care: Angiogenic therapy complements but doesn't replace standard diabetic foot care: glucose control, pressure offloading, infection management, debridement. All remain essential.
Act before amputation becomes inevitable: Tissue death is irreversible. Once extensive necrosis develops, even successful angiogenesis cannot resurrect dead tissue. Earlier intervention offers better prospects for limb salvage.
Learn More About ACP-01 for Diabetic Foot Ulcers:
Visit: hemostemixclinicaltrials.com
Important Note: ACP-01 is currently being evaluated in clinical trials for diabetic foot ulcers and is not yet FDA-approved for general use. Information presented here is for educational purposes and does not constitute medical advice. Consult your physician, wound care specialist, or vascular surgeon about whether regenerative medicine options may be appropriate for your specific condition.