Emerging Therapies in Chronic Wound Healing: Advances in Stem Cell Therapy, Growth Factor Modulation, Mechanical Strategies and Adjuvant Interventions

Abstract

Chronic wounds pose a persistent clinical and economic burden, often failing to respond to standard care as a result of impaired angiogenesis, prolonged inflammation, and dysfunctional cellular activity. Emerging strategies in regenerative medicine offer new hope, particularly those focusing on stem cell therapy, growth factor modulation, and mechanical support. This narrative emphasizes the clinical applicability. We performed targeted searches of PubMed/MEDLINE and Embase using terms related to regenerative cell therapy, growth factor modulation, mechanical/physical strategies, adjuvant therapies, and platelet-derived products (PRP/PRF). We prioritized randomized/controlled studies, high-quality observational cohorts, meta-analyses, and consensus guidelines relevant to chronic wound healing, and we critically appraised heterogeneity and limitations. In particular, the latest innovations in chronic wound management, mesenchymal stem cells (MSCs), and adipose-derived stem cells (ASCs) have shown promise in promoting angiogenesis and modulating immune responses. Concurrently, the targeted delivery of cytokines such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) is being optimized through advanced biomaterials to enhance healing microenvironments. Mechanical interventions, including negative pressure wound therapy (NPWT) and shock wave therapy, further support tissue repair and revascularization. Together, these approaches reflect a shift from symptomatic wound care to personalized, regenerative strategies. This review synthesizes preclinical and clinical data, explores translational challenges, and outlines future directions that integrate biology, bioengineering, and digital tools for optimized wound healing.

Key Summary Points

Stem cell therapies, particularly mesenchymal stem cells (MSCs) and adipose-derived stem cells (ASCs), offer regenerative, angiogenic, and immunomodulatory benefits for chronic wound healing

Cytokine and growth factor therapies, including Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), aim to restore the impaired healing environment in chronic wounds but face challenges related to stability, delivery, and cost

Mechanical therapies like negative pressure wound therapy (NPWT) and mechanobiology-based devices enhance tissue perfusion, granulation, and cellular mechanotransduction critical for healing

Future strategies focus on integrating multimodal, personalized approaches combining stem cells, growth factors, and mechanical support, guided by smart delivery systems and predictive analytics

Introduction

Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure injuries, represent a substantial health problem worldwide, affecting millions and imposing high economic costs [1]. Standard therapies often fail to achieve complete healing because of persistent inflammation, impaired angiogenesis, and poor cellular responses. Despite extensive laboratory and clinical research, no single treatment has proven universally effective for all wound types. Therefore, adjunctive and regenerative therapies have emerged to address the underlying biological dysfunctions and promote sustainable tissue repair [2].

This review explores the latest advances in stem cell therapy, cytokine/growth factor modulation, and chemical/mechanical strategies to enhance chronic wound healing. These therapies have become essential in managing complex wounds, improving outcomes by enhancing the body’s natural healing mechanisms by providing solutions for wounds that fail to heal with conventional treatments, leveraging advanced technologies and biological mechanisms to accelerate recovery and improve quality of life.

Wound healing is a complex cascade involving the interaction of inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells in injured tissue. These cells contribute to wound healing by releasing various chemo-cytokines, growth factors that promote cell migration to the injured area and stimulate inflammation, angiogenesis, wound contraction, and remodeling, resulting in a healthy wound-healing process. The first phase of wound healing begins with the inflammation phase, which starts within 6–8 h after injury. During this phase, platelets migrate to the tissue and release chemoattractive cytokines; next, macrophages arrive and phagocyte/debride the tissue/organisms and set the stage for the proliferative phase. The proliferative phase starts around 5–7 days after injury and is initiated by cytokines released from macrophages (platelet-derived growth factor [PDGF], transforming growth factor [TGF]-α/β, fibroblast growth factor [FGF], etc.). In this stage, the formation of granulation tissue occurs with fibroblast proliferation and extracellular matrix (ECM) deposition. During this phase, angiogenesis occurs, which allows leukocyte migration and provides nutrients and oxygen to develop granulation tissue. The final stage is tissue remodeling, in which wound contraction and ECM reorganization occurs over several months to years, transitioning into mature scar formation. Overall, an efficient wound-healing process results from a sufficient supply of growth factors, nutrients, cell–cell interactions, and adequate oxygenation to the tissue. Disruptions in these mechanisms, caused by conditions such as infection, malnutrition, chronic disease, or diabetes, can lead to delayed wound healing and chronic wound formation. Despite addressing systemic factors (controlling blood glucose levels, optimizing oxygenation to the tissue, providing local wound care), chronic wound care only achieves moderate success and treatment options are limited [3].

This article is a review and does not involve new studies with human participants or animals performed by any of the authors. The authors confirm that the work complies with the journal’s ethical standards. The figures are all original and do not require permissions.

Stem Cell Therapy in Chronic Wound Healing

Stem cell-based interventions have gained significant attention due to their regenerative, immunomodulatory, and paracrine effects [4]. Mesenchymal stem cells (MSCs), derived from bone marrow, adipose tissue, or umbilical cord, are among the most widely studied for wound applications [5]. These cells secrete a variety of bioactive factors that promote angiogenesis, suppress inflammation, and stimulate the migration and proliferation of resident skin cells [6] (Fig. 1).

Fig. 1.

Comparison of the characteristics of three key stem cell types used in regenerative medicine: bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived regenerative cells (ADRCs), and induced pluripotent stem cells (iPSCs). The graphic summarizes their tissue source, differentiation potential, clinical applications, immunogenicity, ease of harvesting, culture complexity, and therapeutic potential across various medical fields

Adipose tissue has emerged as a rich and accessible source of therapeutic cells. Adipose-derived regenerative cells (ADRCs) are a heterogeneous mix of regenerative cells, including stem, progenitor, and immune-regulating cells, isolated directly from adipose (fat) tissue with minimal processing. In contrast, adipose-derived stem cells (ASCs) are purified multipotent stem cells specifically isolated and cultured from adipose tissue, characterized by their targeted regenerative abilities and differentiation potential.

ADRCs, a heterogeneous population obtained via enzymatic digestion or mechanical processing of lipoaspirate, have also shown promise. They are found in the stromal fraction of the adipose tissue and are defined as CD45-negative, CD90-, CD73-, and CD105-positive cells. Unlike other stem cells, ADRCs can easily be collected without any ethical problems and differentiate into different cell lines including adipogenic, osteogenic, chondrogenic, and myogenic cells (Fig. 2). Thus, ADRCs are studied extensively as one of the leading sources in stem cell therapy for regenerative medicine [7, 8].

Fig. 2.

Therapeutic role of adipose-derived regenerative cells (ADRCs) in wound healing. ADRCs are isolated from adipose tissue, which contains various supportive cell types. Once harvested, ADRCs can differentiate into multiple lineages such as endothelial cells, chondrocytes, and neurons and contribute to tissue repair through mechanisms like angiogenesis, anti-inflammation, and cell proliferation, ultimately accelerating wound healing

ADRCs can be applied directly to wound beds without the need for culture expansion, offering a more practical, point-of-care solution [9].

Recent clinical trials have demonstrated improved wound closure rates, enhanced vascularization, and reduced scar formation with stem cell-based therapies [10]. Studies have suggested that ADSCs (adipose-derived stem cells) can promote wound healing with paracrine activity with the aforementioned chemokines [11–13]. Skin wounds treated with ADSCs have been shown to exhibit enhanced healing rates and less scar formation. It was shown that the human epidermal keratinocyte migration rate was increased when co-cultured with ADSCs [14].

Yasuhiko et al. demonstrated that cryopreserved (frozen) ADRCs retain significant therapeutic potential for treating burn wounds. Even after freezing and thawing, the cells effectively promoted wound healing by enhancing tissue regeneration, reducing inflammation, and improving vascularization at the injury site. These results suggest that cryopreserved ADRCs could offer a practical and effective off-the-shelf stem cell therapy option for burn injuries without compromising therapeutic efficacy [15].

Stem cells harvested from different sources can be used for wound repair and regeneration such as endothelial progenitor cells (EPCs), adult stem cells in the forms of bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue stem cells (ASCs), dermal stem cells (DSCs), and inducible pluripotent stem cells (iPSs). These stem cells enhance wound healing via tissue regeneration through paracrine signaling and growth factor release, resulting in fibroblast proliferation and tissue remodeling [16].

In a case–control study involving 75 patients with chronic wounds, 50 were treated with autologous bone marrow (BM) aspirate, either fresh or cultured, while 25 received daily saline dressings. Notably, both the fresh and cultured BM aspirate, even without specific identification, isolation, and selective application of stem cells, led to a significant reduction in wound surface area compared to the control group at day 7 and week 4 [17].

To maximize the therapeutic potential of stem cells, Japanese researchers have explored combining MSCs with bioengineered scaffolds and hydrogel matrices. A study introduced a novel hydrogel containing MSCs, which provided structural support while facilitating cell survival and proliferation. This approach significantly enhanced wound contraction and collagen deposition in animal models, paving the way for its clinical application [18, 19].

iPSCs are pluripotent stem cells derived from somatic donor cells that are generated via overexpression of Oct4, Klf4, Sox2, and c-myc transcription factors in adult somatic cells harvested from healthy objects. iPSCs have the capacity to differentiate into and repopulate all cell types found in the skin [20].

Human-induced pluripotent fibroblasts, human-induced pluripotent MSCs, and human-induced pluripotent stem-cell-derived vesicles have the potential to accelerate wound healing [21].

Despite encouraging results, challenges remain. At present, iPSC-derived products are not in clinical use for chronic wound management. Key barriers include risks of tumorigenicity and genomic instability, variable differentiation fidelity and phenotypic drift, potential immunogenicity, and unresolved issues in Good Manufacturing Practice (GMP)-grade manufacturing, scale-up, cost, and regulatory oversight. Consequently, iPSC research in wound healing remains preclinical/early-translational, with nearer-term clinical activity focused on autologous/allogeneic adult cell products and acellular biologics.

Growth Factor Modulation Therapy

Growth factors play crucial roles in orchestrating wound healing by modulating inflammation, cell migration, proliferation, and angiogenesis [22]. However, in chronic wounds, endogenous levels of key growth factors are often deficient or dysfunctional.

Several recombinant growth factors have been developed for therapeutic use. Platelet-derived growth factor (PDGF) was among the first approved by the FDA for diabetic foot ulcers [23]. Vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) have also been investigated extensively, showing the ability to enhance angiogenesis and re-epithelialization in preclinical models and clinical settings (Table 1) [24].

Table 1.

Clinical applications of key growth factors in wound healing

	Growth factor
	PDGF (Regranex®)	VEGF	EGF (Heberprot-P®)
Route of administration	Topical	Topical	Topical or intralesional injection
Type of wound treated	Diabetic foot ulcer	Diabetic foot ulcer	Burns, non-healing ulcers, diabetic foot ulcers
Mechanism of action	Maintains cell growth and division Chemoattractant for mesenchymal cells Promotes angiogenesis	Enhances angiogenesis Stimulates proliferation and migration of endothelial cells	Stimulates keratinocyte proliferation and migration Enhances tensile strength of new skin Induces fibronectin production
Limitations	Increased cancer risk at high doses Limited efficacy in pressure and venous ulcers	Few clinical applications in wound healing Primarily used in cancer therapy to inhibit tumor angiogenesis	Rapid degradation by matrix metalloproteinases Lack of sustained delivery systems Pain at injection site

VEGF vascular endothelial growth factor, PDGF platelet-derived growth factor, EGF growth factor

Emerging strategies aim to improve the stability and localized delivery of growth factors through encapsulation in hydrogels, nanoparticles, or scaffold systems [25]. Moreover, combination therapies such as simultaneous application of multiple growth factors or pairing with stem cells are under investigation to replicate the complex signaling environments of physiological wound healing [26, 27]. Nonetheless, the translation of growth factor therapies remains limited by issues such as short half-lives, high production costs, and potential off-target effects.

Platelet-Derived Extracellular Vesicles

Platelet-derived extracellular vesicles (EVs/exosomes) are nanoscale vesicles enriched with bioactive cargo (proteins, lipids, miRNAs) that can promote neovascularization, stimulate fibroblast migration, and modulate inflammation and scarring in chronic wounds. Practical translation hinges on upstream choices (donor sourcing), isolation/purification methods and quality control, and stability/storage, and emerging strategies include combining EVs with advanced dressings/hydrogels, co-administration with MSC/M2-derived EVs, or microneedle delivery to improve tissue bioavailability. These opportunities sit alongside persistent standardization needs (isolation/characterization, potency assays, dosing) and evolving regulatory pathways [28].

Early human data support safety: in a first-in-human, double-blind, placebo-controlled phase I study in healthy adults (Plexoval II; ACTRN12620000944932), single-dose allogeneic, ligand-based exosome affinity purification (LEAP)-purified platelet EVs were safe and well tolerated; as expected in this acute model with rapid baseline healing, time to closure did not differ from placebo. These findings justify efficacy-focused trials in patients with delayed or chronic wounds, with adherence to community guidance (e.g., minimal information for studies of extracellular vesicles, MISEV) and rigorous clinical endpoints [29].

Mechanobiological Interventions

Studies conducted at the Mechanobiology Laboratory of Nippon Medical School have demonstrated that areas of high skin tension and stretching such as the chest, shoulders, and knees are particularly susceptible to keloid formation, suggesting that mechanical force may play a role in localized inflammation and fibroblast activation [30, 31].

Additionally, recent research has shown that mechanosensitive pathways, particularly those involving YAP/TAZ signaling, are upregulated in areas of high mechanical stress. These pathways activate fibroblasts, which produce excess collagen and contribute to the exaggerated appearance of hypertrophic scars [32].

Various advanced therapies have been developed to enhance healing, reduce complications, and improve outcomes. These therapies utilize mechanical, electrical, and pressure-based principles to address different stages of the healing process, from initial wound closure to long-term tissue regeneration and scar remodeling. Among the most widely used modalities are negative pressure wound therapy (NPWT), extracorporeal shock wave therapy (ESWT), ultrasound therapy, and compression therapy (Table 2).

Table 2.

Mechanotherapy-oriented mechanical interventions in wound healing

Therapy	Mechanism (mechanotherapy focus)	Advantages	Key references
NPWT	Enhances granulation via mechanical stretch and strain-induced signaling	Increases perfusion, controls exudate, accelerates contraction	Orgill & Bayer [33];
ESWT	Promotes wound and scar healing by enhancing neovascularization, stimulating cell proliferation, remodeling collagen, reducing inflammation, recruiting stem cells, and disrupting biofilms through mechanotransduction	Promotes directional healing and angiogenesis	Yang et al. [34]
Ultrasound therapy	Induces micro-mechanical vibrations enhancing fibroblast and ECM dynamics	Improves debridement and cellular responsiveness	Cacchio, A., et al. [35]
Compression therapy	Alters mechanical load; reduces interstitial pressure and edema	Improves venous return, mechanical support of healing tissue	Vowden & Vowden [36]

ECM extracellular matrix, ESWT extracorporeal shock wave therapy, NPWT negative pressure wound therapy

Each of these methods has demonstrated significant clinical benefits and is increasingly incorporated into modern treatment protocols for both acute and chronic wounds [33].

Negative Pressure Wound Therapy

NPWT is a well-established modality that applies controlled suction to the wound bed, promoting granulation tissue formation, reducing edema, and enhancing perfusion [37].

This pressure induces several effects on the tissue. It enhances cellular mechanotransduction, where cells sense and respond to mechanical forces, which leads to increased proliferation of fibroblasts and keratinocytes, key for tissue regeneration. The therapy also stimulates angiogenesis, increasing the formation of new blood vessels by boosting the expression of VEGF, thus improving blood supply to the healing tissue. Additionally, NPWT promotes granulation tissue formation by inducing cell migration and enhancing the synthesis of ECM components like collagen, necessary for wound closure. The pressure also drains excess fluids, reducing edema and inflammation, which creates a favorable environment for healing [38] (Fig. 3).

Fig. 3.

Clinical progression of a chronic foot wound treated with negative pressure wound therapy (NPWT). Images show the wound before treatment, during NPWT application, and significant healing observed 8 weeks after therapy

More recently, mechanobiology-based interventions, including devices applying cyclic strain or shear forces, have been explored to stimulate cellular responses beneficial for tissue regeneration [39]. Combining mechanical therapies with biologics (e.g., NPWT plus stem cells or growth factors) is a growing area of interest, aiming to synergistically enhance healing [34].

Extracorporeal Shock Wave Therapy

ESWT uses high-energy acoustic waves, also known as shock waves, directed at the wound or injured tissue. These waves induce mechanical forces that trigger several biological responses. The shock waves create pressure waves that stimulate cells to produce bioactive molecules, leading to enhanced cellular proliferation, particularly of fibroblasts, which are critical for wound closure and collagen formation [40]. Shock waves also boost the expression of VEGF and other growth factors, promoting the formation of new blood vessels (angiogenesis), improving vascularization around the wound, and accelerating tissue repair. Moreover, ESWT promotes the remodeling of collagen fibers, which improves the structural integrity of the healing tissue and helps prevent excessive scar formation. Additionally, ESWT can reduce inflammation and modulate pain through the activation of anti-inflammatory cytokines and disruption of biofilms in chronic wounds [35, 41].

Ultrasound Therapy

Ultrasound therapy uses high-frequency sound waves to generate mechanical vibrations within the tissues. These vibrations create several key effects. Microstreaming and cavitation (formation of gas bubbles) caused by the ultrasound waves increase cellular permeability, allowing better diffusion of oxygen and nutrients to the wound site. The mechanical vibrations stimulate fibroblasts, promoting collagen synthesis and improving the organization of the ECM, which facilitates tissue repair. Ultrasound also stimulates angiogenesis, enhancing blood vessel formation by increasing the expression of VEGF. In addition, ultrasound has anti-inflammatory effects by reducing the levels of pro-inflammatory cytokines, promoting the transition from the inflammatory phase to the proliferative phase of wound healing [36].

Compression Therapy

Compression therapy involves the application of elastic bandages or garments to apply mechanical pressure to the affected area. The mechanical pressure improves venous circulation, reducing edema and enhancing the delivery of oxygen and nutrients to the healing tissue. This process facilitates the healing environment by reducing swelling and improving tissue oxygenation. Compression also promotes fibroblast proliferation and collagen deposition, leading to better wound closure and scar remodeling. Additionally, compression therapy encourages wound contraction, reducing the size of the wound, and helps organize collagen within the ECM, enhancing the tissue’s strength and elasticity as it heals [42].

Photobiomodulation

Photobiomodulation refers to low-level red and near-infrared light emitting diode (LED) irradiation and low-level laser light therapy (LLLT) that can modulate mitochondrial signaling (cytochrome c oxidase), nitric oxide bioavailability, ATP synthesis, and downstream transcriptional programs that support angiogenesis and granulation. Small randomized controlled studies in chronic wounds (e.g., diabetic foot and pressure injuries) suggest improved healing kinetics versus usual care in selected protocols [43]. However, outcomes are variable because of heterogeneity in wavelength, energy density (dose), irradiance, pulsing, and treatment schedules, and a biphasic dose–response is recognized. Adverse events are uncommon; practical considerations include device quality, dosimetry control, and avoidance in photosensitizing contexts. Larger, standardized trials are needed [44].

Adjuvant Oxygen-Based Therapies

Hyperbaric Oxygen Therapy

In plastic surgery, hyperbaric oxygen therapy (HBOT) is regarded as a successful adjunctive therapy for promoting wound healing, reducing inflammatory reactions, and improving flap survival [45].

Keloid incisions are often vulnerable to infection after radiotherapy. HBOT can improve local blood circulation and wound healing by increasing the blood oxygen capacity and tension of the body. On the basis on this capacity, we innovatively applied adjunctive HBOT to keloid treatment and achieved satisfactory results. Oxygen is necessary for hydroxylation of proline and lysine, the polymerization and crosslinking of procollagen strands, collagen transport, fibroblast and endothelial cell replication, effective leukocyte killing, angiogensis, and many other processes [46].

HBOT involves administering 100% oxygen at elevated atmospheric pressures in a specialized hyperbaric chamber. The elevated oxygen levels lead to more oxygen dissolving in the blood plasma, significantly increasing oxygen delivery to hypoxic tissues.

HBOT stimulates new blood vessel formation by enhancing VEGF expression and endothelial cell proliferation. Oxygen is a critical substrate for collagen production, ensuring fibroblasts synthesize strong, well-organized fibers. Which subsequently enhances collagen synthesis.

Moreover, the hyperoxygenated environment inhibits anaerobic bacterial growth and enhances leukocyte function, promoting a cleaner wound bed and results in reduced infections [47].

Topical Oxygen Therapy

Topical oxygen therapy (TOT) can be defined as the administration of oxygen applied topically over injured tissue by either continuous delivery or pressurized systems. While hyperbaric oxygen therapy is expensive, and patients are required to visit a hyperbaric clinic multiple times to receive treatment. TOT can address these disadvantages by offering oxygen therapy that can be delivered in patients’ homes at reduced cost. Oxygen is delivered directly to the wound bed, bypassing systemic circulation [48].

This localized approach is beneficial for chronic wounds where systemic oxygen delivery might be compromised. Mechanisms of action include enhanced cell proliferation, angiogenesis, and bacterial control through oxidative stress.

Studies demonstrate the efficacy of HBOT and TOT in reducing healing time, improving graft survival rates, and enhancing wound outcomes. Patients with diabetic foot ulcers treated with HBOT show significant improvements in wound closure rates and reduced amputation risk.

In burn care, HBOT accelerates epithelialization and minimizes scarring, highlighting its versatility in different wound types [49].

Alongside the beneficial clinical effects of HBOT, several side effects and complications have also been described. The two most frequent complications are middle ear barotrauma (MEB) and claustrophobia. Patients suffering from MEB have ear pain, difficulty with ear equalization, a feeling of pressure, and, in rare cases, rupture of the tympanic membrane with a conductive hearing deficit. Sinus/paranasal, pulmonary, and dental barotrauma are other common complications.

Future Strategies

Another promising strategy for improving wound healing includes the very promising and emerging technology, 3D bioprinting. 3D bioprinting techniques allows the precise deposition of skin structure and functional composition in a layer-by-layer approach directly on the wound itself through an in situ bioprinting technique without the requirement for any long-term incubation. In addition, a combination of 3D bioprinting, sensors, and imaging techniques would improve the wound healing outcomes and gradually lead towards precision medicine. For example, 3D bioprinted hydrogel-based dressing that is integrated with electronic components allows for the real-time monitoring of wound conditions [50]. Although enormous success has been observed in the skin bioprinting field, a few limitations still remain. The major limitation related to skin bioprinting for wound healing is the time required to obtain autologous cells to fabricate skin constructs, which has not yet been sufficiently reduced. Patients with extensive burn wounds require treatment on shorter timescales. Therefore, the current focus of skin bioprinting lies in the acceleration of wound recovery with a reduction of hypertrophic scar tissue.

Challenges and Future Directions

Despite promising advancements, chronic wound healing therapies continue to face significant challenges. The heterogeneity of wounds, influenced by patient-specific factors such as age, comorbidities, and wound etiology, often leads to variable treatment responses and complicates clinical outcomes. Moreover, limitations on regeneration in advanced tissue loss may exist. For instance, in chronic wounds with pronounced tissue destruction, e.g., severe ischemia and fibrosis, composite defects after infection or radiation, biologic, or cellular therapies may improve granulation and local biology but are unlikely to fully reconstitute complex anatomy. In such contexts, timely escalation to reconstructive strategies (skin grafts, local/regional/free flaps), offloading/vascular optimization, and infection/biofilm control is essential. Realistic goals should prioritize durable closure, function, pain reduction, and quality of life rather than complete anatomic restoration. Additionally, the lack of standardization in stem cell isolation techniques, growth factor delivery methods, and mechanical therapy protocols makes it difficult to compare results across studies and establish best practices. Regulatory hurdles and high economic costs further slow the translation of innovative therapies from research to widespread clinical use. Looking ahead, future research must focus on developing personalized, multimodal treatment approaches that are tailored to the unique biological characteristics of individual wounds. Advances in smart delivery systems, such as stimuli-responsive hydrogels, may offer better control over the spatial and temporal release of therapeutic agents, while the integration of artificial intelligence could help predict healing trajectories and optimize therapy selection, paving the way for more effective and efficient wound care solutions.

Conclusion

Next-generation therapies for chronic wound healing increasingly integrate regenerative medicine and advanced adjunctive technologies. Stem cell therapy, growth factor modulation, and mechanical interventions each offer unique benefits and, when used synergistically, hold the potential to transform outcomes in patients with refractory wounds. Continued multidisciplinary research and innovation are essential to realize the full potential of these approaches and bring effective, personalized solutions to clinical practice.

Author Contributions

Mohamed Abdelhakim: Conceptualization, literature review, drafting and revising the manuscript. Rei Ogawa: Critical revision of the manuscript for important intellectual content, supervision, and overall guidance. All authors contributed to the development of this manuscript, reviewed the content critically for intellectual value, and approved the final version of the manuscript in line with ICJME requirements.

Funding

No funding or sponsorship was received for this study or publication of this article.

Declarations

Conflict of Interest

Mohamed Abdelhakim has nothing to disclose. Rei Ogawa is an Editorial Board member of Dermatology and Therapy. Rei Ogawa was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethical Approval

This article is a review and does not involve new studies with human participants or animals performed by any of the authors. The authors confirm that the work complies with the journal’s ethical standards. The figures are all original and do not require permissions.