Consider this: a condition that affects nearly one in three people with diabetes over their lifetime, carries a five-year mortality rate rivaling many cancers, and drives more than 85% of all diabetes-related amputations has seen almost no transformative innovation in nearly 30 years. That condition is the diabetic foot ulcer (DFU), and it is long overdue for a reckoning.
A disease seen by all, but owned by few
Wound medicine is one of the most inherently multidisciplinary fields in all of healthcare. Caring properly for a diabetic foot ulcer requires coordinated effort from primary care physicians, podiatrists, vascular surgeons, infectious disease specialists, wound care nurses, nurse practitioners, physical therapists, plastic and reconstructive surgeons, among many others. On any given day, a single patient may require input from half a dozen different providers.
Compounding this fragmentation is an institutional gap: wound medicine is not a board-certified specialty under the American Board of Medical Specialties. There is no single recognized governing society with the authority to unify clinical guidelines, set training standards, or advocate collectively for patients. Instead, each stakeholder specialty develops its own guidelines relevant to its domain.
For patients, this is more than an administrative inconvenience. Chronic wounds demand clinicians willing to act outside of their defined role, not because the system incentivizes it, but because without it, the wound will not heal.
The biology of a wound that cannot heal itself
Diabetic foot ulcers do not form in a vacuum. They are the downstream consequence of years, often decades, of physiological damage. Peripheral neuropathy renders the feet insensate; patients literally cannot feel pressure points forming. Structural changes from long-standing diabetes alter foot mechanics, creating abnormal weight distribution that accelerates breakdown of skin and soft tissue. And peripheral arterial disease, present in approximately 50% of DFU patients, reduces blood flow to the extremities, robbing the body of its natural capacity to heal.
Once an ulcer forms, these same factors conspire against healing. The patient cannot feel the wound, so continues walking on it. Blood flow is insufficient to mount an effective healing response. Normal wound healing progresses through defined phases, but in the DFU patient, this sequence is disrupted. The wound becomes arrested in a chronic inflammatory state. Bacteria colonize the wound bed; biofilms form. Surrounding skin cells become senescent and exhausted. The wound essentially forgets how to heal.
A cascade with a severe end point
Left unaddressed, the consequences of a DFU follow a well-documented and destructive sequence. Infection, which affects approximately 60% of DFUs, becomes the primary driver of emergency department visits and hospitalizations. Osteomyelitis, or bone infection, occurs in roughly 15% of DFU cases, and when present, the amputation rate climbs sharply, approaching 90% in cases of severe infection combined with osteomyelitis. Even after removal of dead and infected tissue, up to 25% of patients with diabetic foot infection have persistent infection after 10–20 days, and 10–45% require readmission within one year.
Ultimately, the lifetime incidence of lower-extremity amputation among people with diabetic foot ulcers is approximately 20%. And here is a number that should stop every policymaker and payer in their tracks: 85% of diabetes-related amputations are preceded by a foot ulcer. That means the overwhelming majority of lower extremity amputations in this country are potentially preventable, if the wound is closed quickly.
Following amputation, five-year mortality reaches 50-70%,. The lifetime risk of developing a DFU is now estimated at 19–34% among people with diabetes, and it is rising as diabetes prevalence grows and our population ages. In some regions, lower extremity amputation rates have increased by as much as 50% over recent the past several years, particularly among younger patients and racial and ethnic minority populations.
Three decades of product development without a biologic approved
Given this burden, one might expect the wound care market to have experienced the kind of transformative therapeutic innovation seen in oncology, cardiovascular disease, or immunology. It has not. The last biologic therapy that received Biologics License Application (BLA) approval from FDA for a common chronic wound indication was in 1997.
The product landscape for chronic wounds has been dominated by advanced dressings and skin substitutes derived from synthetic matrices, animal tissue, or donated human tissue. While there has been a genuine explosion in branded products within these categories, the underlying advances have been incremental; new configurations of the same materials, improvements in convenience and ease of use, rather than therapies that address the root biological causes of wound chronicity.
Much of the innovation has focused on improving existing technologies rather than fundamentally addressing the underlying biology of chronic wounds.
Where the science is headed
What the oncology field has demonstrated over the past decade is that many intractable diseases may yield to therapies built from the patient’s own biology. Autologous cell therapy has substantially improved outcomes in certain hematologic malignancies, establishing proof of concept that cell-based therapies can alter the underlying course of disease. Whether analogous cell-based strategies can achieve meaningful benefit in chronic wounds is an active area of scientific investigation.
A diabetic foot ulcer is, at its core, a wound that lacks the patient’s own functioning skin cells. Traditional reconstructive surgery recognizes this reality and largely relies on autologous tissue, but those approaches struggle in the DFU setting because of the very same factors that cause ulcers: poor blood supply, insensate feet, high pressure, and systemic inflammation.
A variety of investigational regenerative medicine approaches are currently being evaluated, including autologous cellular therapies, exosome-based approaches, gene-based strategies, and other biologic technologies. Whether any of these approaches will ultimately demonstrate meaningful clinical benefit remains under active investigation.
Continued scientific investigation across multiple regenerative approaches may help expand future treatment options.
Closing wounds to give patients their lives back
For a patient with a DFU, wound closure is not simply the absence of an open wound. It means fewer clinic visits, fewer hospitalizations, fewer dressing changes, less drainage, less home nursing. It means greater mobility, restored independence, and freedom from the constellation of oppressive downstream complications that make life with an unhealed DFU so difficult.
Most importantly, it means breaking a sequence of events that leads to amputation and premature death. We know that a foot ulcer precedes amputation in more than 85% of diabetes-related amputations. Closing ulcers quickly is a clear intervention point in that sequence.
For the millions of patients living with diabetes and at risk for foot ulceration, it offers an opportunity to reduce the risk of downstream complications.
Picture: tuk69tuk, Getty Images
Dr. Ned Swanson is the President and Chief Medical Officer at PolarityBio, where he drives the strategic vision and clinical development of innovative therapeutic solutions. Dr. Swanson brings a unique interdisciplinary perspective to regenerative medicine, holding an MD from Harvard Medical School and a degree in Bioengineering from the University of Pennsylvania. He further refined his clinical acumen and surgical skills during his Plastic Surgery residency at Johns Hopkins.
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