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Understanding and Managing Chronic Wounds in Diabetic Patients

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Navigating Acute and Chronic Wounds: From Healing Mechanisms to Innovative Therapies

Diabetes refers to a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Its prevalence is increasing worldwide. This trend is mainly driven by sedentary lifestyles, obesity, high-calorie dietary intakes, and population aging in the case of type 2 diabetes, and possibly by environmental, lifestyle-related, and early-life factors in the case of type 1 diabetes.

Among its many complications, chronic wounds represent a significant burden for both patients and healthcare systems. Diabetic patients are often affected by these wounds due to multifactorial impairments in wound healing, involving vascular, neuropathic, immune, and biochemical dysregulations. They are more prone to developing chronic wounds than the general population, with estimates suggesting that between 20% and 33% of individuals with diabetes mellitus will develop a chronic, non-healing wound in their lifetime.

These wounds contribute significantly to morbidity, reduced quality of life, psychosocial consequences, and increased healthcare costs. Beyond their local impact, chronic wounds in diabetic patients trigger a cascade of systemic effects, including infections, hospitalizations, and, in severe cases – which remain relatively frequent – limb amputations.

As diabetes becomes more prevalent, the incidence of chronic wounds is likewise expected to increase, highlighting the urgent need for better understanding and management of these complications. Although promising therapeutic developments are emerging, their implementation in routine clinical practice remains challenging.

Diabetes and Chronic Wounds

Patients with diabetes are particularly susceptible to chronic wounds, defined as lesions that fail to proceed through the normal healing phases, typically remaining unhealed after 12 weeks. According to the Wound Healing Society, chronic wounds are classified into four main categories based on their underlying causes, each presenting distinct characteristics in terms of typical location, depth, and appearance: pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers.

Leg and foot ulcers are the most common types of wounds and debilitating type of chronic wound in individuals with diabetes, affecting an estimated 19–34% of this population during their lifetime. Notably, approximately 61% of DFUs become infected, and 15% of affected patients ultimately require amputation. These wounds are not only challenging to heal but also highly recurrent, with recurrence rates of up to 40% of DFUs within one year and 65% within five years. Despite this high prevalence, no reliable predictive methods currently exist to anticipate the onset of DFUs.

Other wound types linked to diabetes include:

  • Arterial Ulcers: Diabetes is a major risk factor for arterial ischemic ulcers, more prevalent among the elderly population. These ulcers result from insufficient blood flow into the peripheral blood vessels, leading to severe pain. Around 2.1% of individuals with diabetes develop arterial ulcers.

  • Venous Ulcers: Diabetes increases the risk of venous ulcers, often as a complication of chronic venous disease. In diabetic patients, particularly among the elderly, venous leg ulcers (VLUs) are a common form of chronic leg ulcer, largely due to age-associated neuropathy and localized ischemia.

  • Pressure Ulcers: Diabetes mellitus is an independent risk factor for pressure ulcers, associated with an approximately twofold increase in perioperative risk and nearly double the incidence of pressure ulcers compared to non-diabetic individuals. This risk is further exacerbated by comorbidities such as obesity and hypertension. Diabetes influences pressure ulcer development both directly – through poor perfusion and skin alterations – and indirectly via lack of sensation perception in all medical settings.

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Pathophysiological Mechanisms Underlying Chronic Wounds in Diabetes

Wound healing is a complex, finely coordinated process that is significantly impaired in individuals with diabetes. The pathophysiology involves vascular, neuropathic, immune, cellular, and biochemical disturbances such as persistent hyperglycemia and hypoxia – often interconnected – that prevent normal progression through the healing phases.

The main mechanisms include:

  • Microvascular and Macrovascular Dysfunction: Chronic hyperglycemia levels result in both macrovascular and microvascular complications, which are united by a common platform of endothelial impairment. This vascular impairment compromises blood flow to the wound, reducing oxygen and nutrient delivery, and thereby hindering the healing process.
  • Peripheral Neuropathy: Peripheral neuropathy of the lower extremities affects approximately 66% of individuals with diabetes, with distal sensory neuropathy being the most common type. This latter is a major risk factor for DFU and can present with a wide range of symptoms, from severe pain to a completely painless form, which may present with an insensitive foot ulcer.
  • Impaired Immune Response: Diabetic wounds are characterized by persistent inflammation leading to impaired healing. In normal wound healing, the initial phase involves the rapid recruitment of inflammatory cells, particularly neutrophils and macrophages. However, in diabetic patients, neutrophil recruitment is delayed. In line with this, Sawaya et al (2020) demonstrated a decrease in both macrophage and neutrophil presence in DFUs. The dysregulation of innate immune cells – especially macrophages and their impaired interaction with neutrophils – plays an essential role in disrupted wound healing. A hallmark of diabetic wounds is the prolonged inflammatory phase, largely driven by defective macrophage polarization, where the transition from a pro-inflammatory M1-like phenotype to a pro-healing/anti-inflammatory M2-like phenotype is disrupted. In parallel, pro-inflammatory cytokines such as TNF-α and IL-6, which are essential in wound closure and repair, become dysregulated in diabetic wounds, promoting a chronic inflammatory state and impairing tissue regeneration. This inflammatory imbalance contributes to an unfavorable microenvironment for healing.
  • Defective Phagocytosis and Infection Susceptibility: The dysfunction of phagocytic cells further exacerbates this condition by impairing bacterial clearance, leading to increased intracellular bacterial load and an overall heightened susceptibility to infections.
  • Altered Cellular Function: Keratinocytes and fibroblasts exhibit diminished migration and proliferation, and in the case of keratinocytes, this leads to insufficient re-epithelization of the wound, thereby delaying tissue regeneration.
  • Growth Factor Deficiency: Decreased expression and availability of growth factors such as VEGF, PDGF, and EGF further delay the healing process by impairing angiogenesis, growth and movement of different types of cells, fibroblast chemotaxis, and matrix remodeling.
  • Impaired Angiogenesis: Endothelial dysfunction represents an underlying obstacle to effective wound healing in diabetes. This impairment stems from a multifactorial process particularly involving increased reactive oxygen species (ROS), the accumulation of advanced glycation end products (AGEs), decreased growth factors and cytokines, and altered immune cell response. As a result, angiogenesis is impaired, and when combined with a persistent inflammatory state, this hinders the progression of wound healing.
  • Extracellular Matrix (ECM) Imbalance: Diabetes is associated with impairment in the regulation of extracellular matrix (ECM), whose build-up is modulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).
  • Microbial Infection and Biofilms: Diabetic wounds are highly susceptible to microbial invasion, often resulting in the formation of biofilms, which contribute to persistent, life-threatening infections and significantly delay wound closure.
  • Other contributing factors: Additional factors, including oxidative stress, specific metabolic deficiencies, impaired physiological responses – such as hypoxia resulting from glycation of hemoglobin and alterations of red blood cells membranes and narrowing of blood vessels – further exacerbate wound chronicity.

The Dangers of Untreated Wounds: Risks and Complications

Impaired healing of diabetic wounds affects an estimated 25% of individuals with diabetes mellitus. If left untreated or inadequately managed, these chronic wounds can rapidly deteriorate, frequently resulting in severe clinical complications and incurring subsequent high psychosocial and economic burdens.

  • Infections & Gangrene: Diabetic wounds are highly susceptible to local and systemic infections, which may evolve into cellulitis, myositis, abscess formation, osteomyelitis, and septicemia . In more advanced cases, tissue necrosis may occur, potentially leading to gangrene. These complications often require aggressive treatment and hospitalization.
  • Amputation: Chronic diabetic wounds, irrespective of their anatomical location, may progress to limb amputation in advanced cases. Among these, DFU represent the principal cause of non-traumatic lower extremity amputation worldwide. Notably, DFUs precede approximately 85% of all lower limb amputations, and over 60% of such amputations occur in patients with diabetes. Contributing factors primarily include lower limb vascular disease, neuropathic abnormalities and prior vascular ulcers, poor glycemic control, the presence of infections, and the coexistence of multiple ulcerations.
  • Psychosocial Impact: Chronic wounds – especially DFU – profoundly affect patients’ quality of life. They contribute to pain, impaired mobility, and emotional distress. Emotional consequences reported include feeling sadness, fear, frustration, anxiety, loss of social confidence, powerlessness, uncertainty about the future, loss of independence, social isolation, an altered sense of self, and body image disturbance. Vileikyte et al (2020) emphasized that the loss of mobility caused by non-weight-bearing treatment is central to individuals’ experience with DFU, resulting in restrictions in activities of daily living. Moreover, several studies have demonstrated that health-related quality of life significantly improves with DFU healing, while it deteriorates in cases of non-healing or recurrence.
  • Economic Burden: Chronic diabetic wounds – particularly DFU – are associated with a significant increase in healthcare expenditures. This economic burden is primarily driven by prolonged hospitalizations, surgical procedures, outpatient/physician office visits, emergency department visits, days requiring home health care, and specialized wound care including antibiotic therapy and dressings. Rice et al (2014) reported that DFUs impose a substantial burden on public and private payers, ranging from $9-13 billion annually, in addition to the baseline costs associated with diabetes itself. Additionally, some patients face economic stress due to medical care costs and job loss.

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Managing Wounds in Diabetic Patients: Key Approaches

The cornerstone of diabetic wound management – particularly for DFUs – involves a comprehensive assessment of wound characteristics. This includes evaluating location, extent, size, depth, the type of tissue involved, presence of infection, and duration, primarily through physical and vascular examinations. Based on these findings, clinicians determine whether the patient can be treated as an outpatient or requires hospitalization.

The standard practices in diabetic wound management, particularly DFUs, involve a multifaceted approach, which typically include:

  • Assessing the ulcer grade classification,
  • Surgical debridement,
  • Appropriate dressings to maintain a moist wound environment and exudate control,
  • Off-loading,
  • Vascular assessment (status and presence of a chance for interventional vascular correction),
  • Infection control, glycemic management,
  • The use of adjuvant therapies such as:

  • Hyperbaric oxygen therapy (HBOT),
  • Negative pressure wound therapy (NPWT),
  • Topical growth factor therapies,
  • Stem cell therapies,
  • Skin substitutes.

These interventions aim to promote timely and effective wound closure while minimizing the risk of complications and recurrence. They are best coordinated by a multidisciplinary diabetic foot care team or clinic, as diabetic ulcer healing depends on multiple factors.

Given the complexity, early management of diabetic wounds, combined with regular monitoring, is essential to prevent complications. In cases of DFUs, early detection and intervention can promote healing, reduce the risk of amputation, and enhance patients’ quality of life. In light of ongoing clinical challenges, emerging therapeutic approaches – especially stimuli-responsive and multifunctional strategies – that can accelerate diabetic wound healing, holds promise for improving the efficacy of diabetic wound management.

Advances in Treatment: Current Therapies and Ongoing Research

Significant progress has been achieved in the management of diabetic wounds, largely driven by breakthroughs in tissue engineering, regenerative medicine, and precision medicine. Most current and emerging therapies – including conventional approaches and advanced adjuvant strategies – overlap with those previously discussed in our article on chronic wounds. These encompass dressings and topical products, growth factor-based therapies, skin grafts and bioengineered skin, physical methods (e.g., HBOT, NPWT, electrical therapy), platelet-rich plasma (PRP)-based treatment, and systemic therapies.

An area of increasing interest is the repurposing of clinically approved drugs for diabetic wound healing. For example, several antidiabetic medications – including insulin, metformin, some sulfonylureas, thiazolidinediones, and dipeptidylpeptidase 4 (DPP-4) inhibitors – have demonstrated diverse effects such as reduced MMPs activity, enhanced keratinocyte and fibroblast proliferation, and pro-angiogenic effects. However, it remains unclear whether this correlates clinically with improved wound healing, in some cases. Conversely, certain drugs such as anticonvulsants, steroids, antibiotics, angiogenesis inhibitors, and nonsteroidal anti-inflammatory drugs have been involved in disrupting wound healing.

A major concern in diabetic wounds is their high susceptibility to microbial colonization, particularly by biofilms. These polymicrobial biofilms are often underestimated in clinical settings, but may be responsible for the delayed healing and consequent infection chronicity in diabetic wounds, particularly in DFUs, despite the use of systemic antibiotic therapy. Appropriate treatment for the elimination of these microbial communities can halt the disease progression and, in some cases, even prevent more serious outcomes, such as amputation or death. In line with recent guidelines, the management of biofilm-associated DFU infections should follow the principles of biofilm-based wound treatment (BBWC), with a combined approach involving debridement and antibiotic therapy.

Despite the wide range of available treatments and the expanding understanding of diabetic wound healing mechanisms, there are few widely successful clinical therapies specific to diabetic wounds beyond general wound care. This highlights the necessity for more targeted, high-quality studies.

Looking ahead, personalized treatment approaches are expected to play a growing role in diabetic wound management. Smart wound dressings, hydrogels, and other technologies may enable close monitoring and timely interventions – particularly valuable for preventing non-healing wounds from progressing, as patients often fail to recognize the severity of their wounds. In addition, innovative technologies – potentially associated with emerging therapeutic pathways – newly identified therapeutic agents, and combinational approaches offer promising avenues for research and clinical translation.

Future strategies may involve combining therapies that target multiple biological pathways (e.g., modulation of the inflammatory response, disruption of bacterial biofilms) within the same healing phase or span across different healing phases. Such combinatory strategies may be applied simultaneously, sequentially, or in a flexible, adaptive manner – including combinations of bioactive compounds.

Therefore, the effective treatment of chronic diabetic wounds will likely require a multimodal and interdisciplinary approach that integrates precision medicine, advanced materials, and collaborative clinical care.

Market Trends: The Growing Demand for Diabetic Wound Care

The global chronic wound care market, particularly for DFUs, was valued at USD 2.22 billion in 2022 and is expected to reach USD 3.44 Billion by 2030, growing at a CAGR of 7.5% between 2024 and 2030. This robust expansion is mainly driven by the rising global prevalence of diabetes, the increasing prevalence of DFUs, the launch of novel active therapies, and a growing number of amputations related to these DFUs.

Rising diabetes rates in low- and middle-income countries – alongside contributing risk factors such as population aging, sedentary lifestyles, and rising obesity rates – are also anticipated to fuel market growth over the forecast period.

Alongside these epidemiological drivers, heightened awareness about diabetic wound management and improvements in healthcare infrastructure have fostered market growth.

Another major trend is the growing demand for personalized treatment solutions tailored to individual patient profiles.

In response to the worldwide rise in diabetes cases, the market is likely to witness demand for diabetic wound treatment therapies and devices.

However, the market still faces several barriers. The high cost of ulcer management and stringent regulations concerning treatment devices may limit market growth.

From a product standpoint, foam dressings are projected to hold the largest share over the forecast period, supported by recent product approvals within this category. Other categories – such as other wound care dressings, wound care devices, skin grafts, and substitutes, and growth factor-based therapies – are also expected to contribute to market expansion.

Geographically, North America was the largest regional market for diabetic wounds in 2024 and is projected to maintain its leading position in the coming years.

To better illustrate the complexity and segmentation of this dynamic market, Table 1 summarizes the main categories of products, wound types, end-users, and regional distribution.

Table 1. Market segmentation of global chronic wound care.

Product type Wound care dressings: foam dressings, antimicrobial dressings, film dressings, hydrogel dressings, alginate dressings, silver dressings, hydrocolloid dressings, hydro fiber dressings, others;

Wound care devices: NPWT devices, HBOT devices, electric stimulation devices, debridement devices, others;

Skin grafts and substitutes: autografts, allografts, xenografts, synthetic skin substitutes

Growth factors; platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), vascular endothelial growth Factor (VEGF)

Other products: wound cleansers, antiseptics, bandages and tapes
Wound type Neuropathic ulcer wounds, ischemic ulcer wounds, neuro-ischemic ulcer wounds
End-user Hospitals, specialty clinics, others
Regional segmentation North America, Europe, Asia-Pacific, and Rest of the World

Conclusion and Outlook

Chronic wounds in diabetic patients represent a growing and complex challenge, combining the rising prevalence of diabetes with the intrinsic difficulty of achieving effective and lasting wound healing. Despite advances in conventional wound care, diabetic wounds continue to exhibit delayed healing, high recurrence rates, and a significant risk of complications such as infection or amputation, severely impacting patients’ quality of life.

Looking ahead, the integration of advanced therapeutic strategies – including innovative technologies, combinational approaches, and personalized medicine – together with a deeper understanding of diabetic wound pathophysiology, offers promising avenues to improve patient outcomes. However, the development of effective therapies in this field remains highly demanding, as diabetic wounds involve multifactorial impairments (e.g., vascular dysfunction, neuropathy, immune dysregulation) that complicate both preclinical modeling and clinical trial design.

Bringing laboratory innovations to the clinic also presents significant hurdles. Translating these advances into clinically viable treatments requires addressing cost-effectiveness, navigating stringent regulatory frameworks, and ensuring that candidates meet critical criteria such as safety, reproducibility, and therapeutic efficacy.

In this increasingly complex landscape, Contract Research Organizations (CROs) have become essential partners for biotech and pharmaceutical companies seeking to bring innovative diabetic wound therapies to market. Beyond providing technical services, CROs contribute strategic value by supporting the design of disease-relevant preclinical models, the implementation of biomarker-driven clinical studies, and the navigation of complex regulatory pathways. Their multidisciplinary expertise enables sponsors to optimize development timelines, improve data quality, and accelerate the translation of innovative therapies from bench to bedside.

For companies engaged in diabetic wound care R&D, collaborating with a CRO helps to navigate scientific and regulatory complexities while focusing internal efforts on innovation and differentiation. Ultimately, these collaborations are key to transforming scientific progress into tangible clinical benefits for patients, delivering therapies that are innovative, accessible, safe, and capable of truly improving the lives of people with diabetes.

Abbreviations
AGEs, Advance glycation end products; BBWC, Biofilm-based wound treatment; CAGR, Compound annual growth rate; CAP, cold atmospheric plasma; CRO, Contract research organizations; DFU, Diabetic foot ulcer; ECM, Extracellular matrix; EGF, Epidermal growth factor; HBOT, Hyperbaric oxygen therapy; MMPs, Matrix metalloproteinases; NPWT, Negative pressure wound therapy; PDGF, Platelet-derived growth factor; PRP, Platelet-rich plasma; ROS, reactive oxygen species; TIMPs, tissue inhibitors of metalloproteinases; VEGF, Vascular endothelial growth factor; VLU, Venous leg ulcer.

Written by:

Philippe Gentine, PhD

Life Sciences R&D Expert

Edited by:

Mara Carloni, PhD

Scientific Communications & Marketing Project Leader

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