Wounds represent a significant and growing global health burden, affecting millions of individuals worldwide and placing substantial strain on healthcare systems [1]. Chronic wounds, defined as injuries that fail to progress through the normal stages of healing and that remain in a persistent inflammatory state, encompass a wide range of clinical entities. While commonly categorized by etiology into types such as venous ulcers, diabetic foot ulcers, and pressure injuries, they also include less frequently emphasized but clinically significant forms such as arterial ulcers, malignant wounds, and non-healing burns [2]. These chronic wounds are often accompanied by prolonged tissue breakdown, increased risk of infection and a profound negative impact on patients’ quality of life [3,4]. Current estimates suggest that chronic wounds affect 1% to 2% of the population in high-income countries, with even higher prevalence in older adults and individuals with comorbidities such as type 2 diabetes mellitus and peripheral vascular disease [5]. The economic burden associated with their management is staggering, accounting for billions of dollars in healthcare expenditures annually [6]. In the United States alone, chronic wound care costs exceed $25 billion per year [6], with similar trends observed in Europe and other regions [7]. These figures underscore the urgent need for a paradigm shift in understanding and managing chronic wounds.

Despite the clinical and economic significance of chronic wounds, their conceptualization remains fragmented and reductionist [8-11], with classifications primarily based on etiology rather than underlying pathophysiological mechanisms. This framework has resulted in a disjointed approach to diagnosis, treatment, and research, limiting the development of standardized and effective therapeutic strategies [8-11]. Historically, medical science has faced similar challenges in other fields, where conditions initially perceived as heterogeneous disorders were later recognized as syndromes due to shared underlying mechanisms [12,13]. Notable examples include metabolic syndrome, which integrates obesity, dyslipidemia, insulin resistance, and hypertension into a single entity, and systemic inflammatory response syndrome, which unifies diverse inflammatory states under a common physiological framework [12,13]. These shifts in conceptualization have led to more comprehensive diagnostic and therapeutic approaches, improving patient outcomes and advancing medical research.

Drawing from these precedents, we propose that chronic wounds should be redefined as a chronic wound syndrome (CWS): a framework that acknowledges their common pathophysiological pathways rather than focusing solely on their diverse clinical presentations. This shift is not merely semantic but rather an epistemological necessity that aligns with the evolution of medical knowledge [14]. The current classification system, rooted in etiology, fails to capture the complex, multifactorial, and self-sustaining nature of chronic wounds [15,16]. Chronic wounds share fundamental pathophysiological abnormalities, including dysregulated inflammation, impaired angiogenesis, cellular senescence, and extracellular matrix degradation [4,17-19]. These abnormalities are not exclusive to a single type of chronic wound but rather represent a syndromic continuum in which different wounds exhibit varying degrees of the same underlying dysfunctions [4,17-19].

Additional precedents in modern medicine support this epistemological shift. Frailty syndrome, for example, was initially perceived as a vague geriatric construct [20], but its consistent clinical presentation and shared pathophysiological basis, including sarcopenia, chronic inflammation, and endocrine dysregulation, led to its recognition as a multidimensional syndrome [20]. Likewise, post-COVID-19 syndrome has evolved from a poorly defined post-infectious state into a recognized entity with converging mechanisms such as endothelial dysfunction, autonomic imbalance, and persistent low-grade inflammation [21]. These examples illustrate how embracing a syndromic framework has facilitated diagnostic clarity, improved treatment strategies, and enhanced research standardization. Chronic wounds may benefit from a similar conceptual transition.

The aim of this review is to propose and present supporting arguments for epistemologically conceptualizing chronic wounds as a syndrome rather than a specific pathological condition.

The current conceptual framework for chronic wounds suffers from a fundamental epistemological fragmentation that hinders progress in both clinical practice and research [22,23]. Unlike other medical conditions that have transitioned from a fragmented to a syndromic model [12,13], chronic wounds continue to be treated as isolated entities with limited cross-disciplinary integration. This fragmentation manifests in several ways:

· Etiological reductionism: The conventional classification system categorizes chronic wounds based on their primary cause, leading to siloed research and treatment approaches [22,23]. While etiology is clinically relevant, it does not account for the shared molecular and cellular mechanisms that drive chronicity across different wound types [24].

· Lack of standardized therapeutic strategies: Due to the rigid classification system, therapeutic interventions are often developed in isolation for each wound type [22,23], leading to inconsistent treatment guidelines. A syndromic framework would allow targeting of cross-cutting pathophysiological mechanisms, improving consistency and efficacy in care [10,25].

· Barriers to translational research: The current classification hinders the exploration of shared biological drivers of chronicity, delaying the development of universal biomarkers and mechanism-based therapies [26].

· Challenges in clinical trial design: The heterogeneity of chronic wounds poses challenges for the design of clinical trials, particularly in-patient stratification, outcome assessment, and therapeutic response evaluation [27,28]. A syndromic model would enable a more cohesive framework for clinical research, allowing for the identification of patient subgroups based on shared pathophysiological features rather than arbitrary etiological categories.

Therapeutic fragmentation has led to documented clinical failures. For instance, the use of topical growth factors, such as recombinant platelet-derived growth factor (PDGF), has demonstrated variable efficacy when applied based solely on wound etiology [17,18,24,29]. In diabetic foot ulcers, PDGF has shown moderate healing acceleration, while in pressure ulcers with similar histopathological features (e.g., chronic inflammation and matrix metalloproteinases [MMP] overexpression), it often yields poor outcomes due to delayed administration or misaligned therapeutic targets [17,18,24,29]. However, negative pressure wound therapy (NPWT), although initially developed for traumatic and surgical wounds, has demonstrated efficacy in a broad range of chronic wound types, including diabetic foot ulcers, venous leg ulcers, and pressure injuries [17,18,24,29]. This cross-etiological applicability suggests that NPWT exerts its beneficial effects on shared pathophysiological processes, such as reducing excessive exudate, promoting perfusion, and modulating inflammation, rather than on etiology-specific mechanisms. While variations in clinical outcomes may arise depending on individual wound characteristics, the overall therapeutic utility of NPWT across diverse etiologies supports the existence of common biological dysfunctions underlying chronicity. Therefore, rather than contradicting the syndromic model, the broad applicability of NPWT reinforces the notion that chronic wounds share core pathophysiological features that transcend their etiological classification [17,18,24,29].

A conceptual understanding of these limitations and findings are essential for identifying the opportunity to redefine the traditional conception of chronic wounds (Fig. 1). Advancing the knowledge frontier requires applying knowledge construction theories in biomedicine through the cross-disciplinary integration of basic, translational, and clinical sciences [29]. Only through this approach can the full scope of considering chronic wounds as a syndrome be understood, along with its potential to improve specific outcomes in chronic wound healing.

A syndrome is a set of signs, symptoms, and pathophysiological alterations that systematically and recurrently coexist within a defined clinical entity, regardless of its specific cause [30-34]. Unlike a disease, a syndrome does not necessarily have a single, well-defined etiology but rather represents a common pathological response to various underlying conditions [33,34].

The central postulate asserts that chronic wounds should be conceptualized within a syndromic framework, where a series of shared pathophysiological processes underlie diverse clinical manifestations, and provides a reframing beyond the limits of etiological reductionism. Understanding this postulate requires consideration of three key arguments: biological, clinical, and practical, which provide insight into the genesis, progression, resolution, and prognosis of chronic wounds.

Reconceptualizing chronic wounds as a syndrome presents multiple advantages for both clinical management and scientific research:

· Improved clinical management: A syndromic framework would enable the development of comprehensive, standardized treatment protocols targeting common underlying mechanisms [57,58]. Additionally, therapeutic interventions could be tailored based on pathophysiological profiles rather than wound type, leading to more effective and personalized treatments [57,58]. This, in turn, would facilitate the integration of multidisciplinary care approaches, including plastic surgery, dermatology, vascular medicine, endocrinology, and wound care specialists through a shared conceptual framework [57,58].

· Advancement in research and biomarker development: The identification of shared molecular pathways across different chronic wounds could accelerate biomarker discovery, improving early diagnosis and treatment monitoring [59]. A syndromic approach would provide a unifying framework for investigating novel therapeutic targets, fostering innovation in wound healing research. In this context, the potential for repurposing existing drugs targeting inflammation, oxidative stress, and fibrosis could be expanded within a syndromic paradigm.

· Enhanced predictive and prognostic models: Machine learning and artificial intelligence applications in chronic wound management could benefit from a syndromic classification, allowing for more accurate predictive models of wound healing trajectories [60,61]. The development of risk stratification tools based on shared pathophysiological markers would enable earlier intervention and improved patient outcomes [60,61].

· Greater consensus in clinical guidelines and policy development: A syndromic framework would facilitate the development of universally accepted clinical guidelines, reducing variability in treatment approaches across healthcare settings. Policymakers and healthcare administrators could allocate resources more efficiently by recognizing chronic wounds as a unified syndrome with common management strategies.

While the adoption of a syndromic model may initially introduce a degree of complexity to existing treatment guidelines, this complexity is transitional. In the long term, a mechanistic framework would enable the development of streamlined, algorithm-based protocols targeting shared pathological features such as inflammation, cellular senescence, and impaired angiogenesis. This would reduce the fragmentation observed in current guidelines, where distinct protocols exist for each wound type despite overlapping therapeutic needs. Ultimately, a syndromic model would promote simplification through standardization and facilitate the creation of modular guidelines adaptable to diverse clinical contexts.

Under a syndromic framework, treatment guidelines could evolve into mechanism-driven algorithms. Rather than segregating interventions strictly by etiology, clinical pathways would be organized according to dominant pathophysiological traits, such as persistent inflammation, impaired angiogenesis, or cellular senescence, identified through biomarker profiling. For instance, patients with high inflammatory burden (e.g., elevated TNF-α or IL-6) could be directed toward anti-inflammatory or immunomodulatory therapies, regardless of wound type. These guidelines would adopt a modular design, combining foundational interventions (e.g., debridement, offloading, infection control) with targeted adjuncts tailored to the patient’s biological profile. This approach preserves the role of etiological considerations while optimizing therapeutic precision and standardization.

Redefining chronic wounds as CWS opens new avenues for standardizing diagnostic criteria, optimizing treatment strategies, and advancing research methodologies. Future efforts should focus on establishing a shared classification framework that moves beyond etiological distinctions, integrating molecular and pathophysiological markers to enhance early diagnosis and prognosis. The identification of biomarkers and predictive models will be crucial in developing personalized treatment approaches, enabling precision medicine strategies that address the underlying mechanisms rather than treating wounds as isolated conditions [60,61]. Clinical trials should also evolve to assess interventions targeting common inflammatory, angiogenic, and regenerative pathways, ensuring greater translatability across different patient populations [58,59].

From a healthcare perspective, the syndromic approach provides an opportunity to integrate multidisciplinary care models, incorporating dermatology, plastic surgery, vascular medicine, endocrinology, and rehabilitation specialists in a holistic, patient-centric framework. Additionally, artificial intelligence and telemedicine could play a pivotal role in wound monitoring, improving early detection and intervention [62]. Policymakers must also recognize the economic burden of chronic wounds and adjust clinical guidelines and reimbursement policies to support evidence-based interventions that align with this conceptual shift [63]. By embracing a syndromic model, chronic wound management can transition from fragmented, etiology-based approaches to a mechanism-driven paradigm, improving patient outcomes, reducing healthcare costs, and fostering innovation in wound healing research.

The adoption of a syndromic classification could also transform the landscape of research funding, clinical trial design, and health policy. Funding agencies may prioritize mechanism-based research that transcends wound etiology, enabling cross-cutting studies on chronic inflammation, senescence, or angiogenesis across multiple wound types. Clinical trials could benefit from new eligibility criteria based on shared biomarkers rather than lesion type, improving stratification, reproducibility, and external validity. Furthermore, a syndromic model could inform the revision of clinical guidelines and reimbursement policies, allowing for the inclusion of universal therapeutic strategies (e.g., anti-inflammatory agents or senolytics) that target the underlying biology of chronic wounds. These shifts would align healthcare systems with the precision medicine paradigm and foster innovation in wound care delivery.

Chronic wounds meet epistemological, biological, clinical, and practical criteria to be classified as a syndrome rather than a collection of heterogeneous disorders. Epistemologically, medicine has shifted from a reductionist approach to a syndromic model when shared mechanisms have been identified. Recent studies have demonstrated that chronic wounds, despite their diverse etiologies, exhibit common pathological mechanisms. Biologically, a shared pathophysiology unifies chronic wounds into a distinct clinical entity. Clinically, they present a recurring syndromic phenotype, regardless of their underlying cause. From a practical standpoint, conceptualizing chronic wounds as a syndrome would enhance research, diagnosis, and clinical management by integrating multidimensional and multi-level perspectives. This reclassification would improve understanding of their pathophysiology, streamline therapeutic strategies, and drive the development of novel interventions based on common biological mechanisms.