Erfolgreich durch internationale Zusammenarbeit

Dermatology

Cite as: Archiv EuroMedica. 2026. 16; 3. DOI 10.35630/2026/16/Iss.3.18

Received 22 April 2026;
Accepted 1 June 2026;
Published 12 June 2026

SCAR AND WOUND MANAGEMENT: FROM CONVENTIONAL THERAPIES TO ADIPOSE-DERIVED AND EXOSOME-BASED REGENERATIVE APPROACHES

Rafal Žuromskij¹ , Anastasiia Polishchuk²

¹ Medical University of Warsaw, Warsaw, Poland
² Wroclaw Medical University, Wroclaw, Poland

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  Raphal.zuromski@gmail.com

ABSTRACT

Background

Wound healing and scar formation remain important clinical problems, particularly in chronic wounds, hypertrophic scars, keloids and post-surgical or post-burn fibrosis. Conventional treatment can improve scar appearance, but complete functional and aesthetic tissue restoration remains difficult.

Aims

This narrative review summarizes current approaches to wound and scar management, with emphasis on silicone therapy, laser treatment, adipose-derived regenerative methods and exosome-based cell-free therapies.

Methods

A narrative literature review was conducted using PubMed, Google Scholar and ScienceDirect. Peer-reviewed English-language publications from 2013 to 2025 were considered. The review focused on mechanisms of wound healing, scar remodelling, angiogenesis, macrophage polarization, silicone and laser therapy, stromal vascular fraction, nanofat grafting, adipose-derived stem cells and extracellular vesicles. 46 sources were selected for qualitative synthesis.

Results

Silicone gel and laser therapy remain established options for early hypertrophic scar management, mainly through hydration, modulation of fibroblast activity and collagen remodelling. Adipose-derived therapies may support tissue repair by promoting angiogenesis, modulating inflammation and improving extracellular matrix remodelling. Nanofat and stromal vascular fraction are mainly discussed in relation to dermal remodelling and chronic tissue defects. Exosome-based therapies appear promising because of their paracrine and immunomodulatory activity, but current evidence remains less mature and requires clinical standardization.

Conclusions

Conventional methods remain clinically relevant, whereas adipose-derived and exosome-based therapies represent promising regenerative approaches. Their broader clinical use requires stronger comparative evidence, standardized protocols and long-term safety data.

Keywords: hypertrophic scars, pathological scarring, chronic wounds, wound healing, scar management, silicone gel, laser therapy, adipose-derived stem cells, stromal vascular fraction, nanofat grafting, exosomes, extracellular vesicles, regenerative medicine, macrophage polarization, angiogenesis, extracellular matrix remodelling, trichology.

INTRODUCTION

Wound healing is a highly organized natural process divided into four distinct yet overlapping phases: hemostasis, inflammation, proliferation, and remodelling [1–3]. The transition from a fibrin-rich clot to organized tissue requires a precise balance of cellular activity. In normal healing, inflammation subsides as macrophages switch from a pro-inflammatory M1 phenotype to a pro-healing M2 phenotype [4,5]. However, when this balance is disrupted — often due to long-term inflammation or mechanical stress — excessive deposition of extracellular matrix (ECM) components, particularly collagen types I and III, leads to the formation of pathological scars, such as hypertrophic scars and keloids [6,7]. Crucial to this remodeling phase is the balance between Matrix Metalloproteinases (MMPs) and their inhibitors; in pathological scarring, this balance is often lost, leading to an environment where tissue degradation is insufficient and collagen accumulation becomes uncontrollable [3,7,8].

Mechanical tension remains a primary driver of fibrosis. Through a process called mechanotransduction, physical forces are converted into biochemical signals that keep myofibroblasts activated, resulting in thickened and inflexible scar tissue [9]. One of the most significant challenges in modern wound care is the management of chronic, non-healing wounds, particularly the diabetic foot ulcer (DFU). In diabetic patients, impaired microcirculation and peripheral neuropathy lead to a state of chronic inflammation where the normal healing cycle is stalled in the inflammatory phase [10–12]. A major barrier to healing in these patients is the lack of adequate angiogenesis; without the formation of new blood vessels, the wound site remains hypoxic and deprived of essential nutrients [11].

Traditionally, scar management has relied on physical interventions like silicone sheets and gels and laser therapies, which focus on hydration and collagen remodelling [9,13]. While these methods remain gold standards for early intervention, they often focus on symptomatic relief rather than true tissue restoration. This has led to the emergence of mesenchymal stem cells (MSCs), particularly Adipose-Derived Stem Cells (ADSCs), as powerful tools in regenerative medicine due to their immunomodulatory and paracrine effects [10,14]. Modern research emphasizes that the therapeutic power of ADSCs lies primarily in their secretome, a rich cocktail of cytokines and growth factors. This paracrine signalling allows for "cell-free" regeneration through exosomes, which can deliver molecular instructions directly to damaged cells without the risks of live cell transplantation [1,4,15].

Beyond simple scar reduction, Stromal Vascular Fraction (SVF) and Nanofat grafting are increasingly utilized for comprehensive tissue remodelling and aesthetic rejuvenation. These techniques not only improve scar texture but also show substantial promise in trichology, particularly for treating alopecia by stimulating the hair follicle niche and promoting hair restoration in scarred areas [16–18]. Therefore, the aim of this review is to evaluate the clinical evidence for adipose-derived regenerative therapies in wound and scar management, addressing how these modalities modulate the M1/M2 transition, stimulate angiogenesis, and what barriers remain to their universal application [15,19].

AIM

The aim of this work is to summarize current conventional and regenerative approaches to scar and wound management, with emphasis on silicone therapy, laser treatment, adipose-derived therapies, nanofat, stromal vascular fraction and exosome-based methods. The objectives are: to describe the main biological mechanisms involved in wound healing and pathological scar formation; to summarize conventional and regenerative approaches used in scar and wound management; and to discuss current clinical applications, safety concerns and limitations of these methods.

METHODS

This narrative review was prepared to summarize and critically discuss current scientific literature on scar and wound management, guided by the general principles of the Assessment of Narrative Review Articles. Literature was searched in PubMed, Google Scholar and ScienceDirect. During the initial search stage, more than 70 publications were screened, and 46 sources were selected for qualitative analysis.

The search process used keywords covering biological, technical and clinical aspects of scar therapy, including hypertrophic scars, adipose-derived stem cells (ADSCs), exosomes, nanofat, laser therapy, silicone gel, regenerative medicine, wound healing, extracellular vesicles, mechanotransduction, stromal vascular fraction, trichology and macrophages. The selection process prioritized publications with higher relevance and stronger evidence, including meta-analyses, systematic reviews, clinical studies and relevant experimental studies. Duplicate articles and publications without full text availability were excluded, as were papers based only on individual opinions without supporting empirical data.

The selected 46 sources were analysed qualitatively to compare conventional scar management methods, adipose-derived regenerative therapies, nanofat, stromal vascular fraction and exosome-based approaches. The analysis focused on mechanisms of action, clinical applications, reported benefits, safety concerns and current limitations.

RESULTS

Pathophysiology of Scar Formation

The transformation of an acute injury into a permanent scar is a complex journey that can be divided into four distinct phases: haemostasis, inflammation, proliferation, and remodelling [1,2]. Initially, the haemostasis phase creates a temporary fibrin scaffold that acts as a dynamic platform for the secretion of early chemotactic signals coordinating the recruitment of pro-regenerative cell populations. With the onset of the inflammatory phase, neutrophils and monocytes migrate to the site for enzymatic debridement and elimination of microbial pathogens. However, if this phase lasts too long — as is common in diabetic foot ulcers — the body fails to move forward, leading to poor tissue quality [4,10,11].

The proliferation phase is where the actual "building" happens: fibroblasts migrate to the site and begin producing collagen. The most vital part of this process is the remodelling phase, which can last for over a year, during which collagen III is replaced by organized collagen I. The quality of this replacement is heavily influenced by physical tension on the skin. Through a mechanism called mechanotransduction, cells detect the pull on the wound and respond by producing even more collagen, often leading to a "vicious cycle" where tension causes thicker scars such as hypertrophic scars or keloids [6–9].

Macrophage Plasticity: Shifting Macrophage Phenotypes for Tissue Restoration

Current research indicates that macrophages are the primary directors of the wound microenvironment, acting as the biological switch that determines the path toward either regeneration or excessive scarring [4,5,1]. The M1 phenotype (pro-inflammatory) is vital for the initial response, clearing the wound through the release of pro-inflammatory cytokines. However, if the M1 state persists, it causes collateral damage to healthy tissue. To achieve successful healing, these cells must shift into the M2 phenotype (pro-healing), which releases natural signals that suppress excessive inflammation and promote the organization of the collagen matrix [11,15,10].

Modern regenerative strategies, particularly those involving ADSCs, are designed to facilitate this polarization. By forcing the M1 to M2 transition, these therapies reduce the risk of fibrosis and promote a more flexible, natural-looking tissue structure [4,5,7,19]. The specific molecular mediators and signalling pathways through which these adipose-derived therapies orchestrate this immunomodulatory shift are summarized in Table 1.

Traditional Scar Management

Traditional management strategies remain the fundamental basis of current clinical protocols for the prevention and treatment of pathological scars. Occlusive therapy, particularly the application of topical silicone gel and sheeting, is one of the most widely utilized physical interventions. Silicone gel significantly improves the clinical appearance of scars by reducing height, pliability, and pigmentation [9]. The mechanism behind this efficacy is primarily attributed to increased hydration and the normalization of the localized cytokine environment, which subsequently regulates fibroblast proliferation and extracellular matrix deposition [9,24].

Thermal interventions, led by various laser systems, offer a more proactive approach by inducing controlled tissue remodelling. Modalities such as fractional carbon dioxide (CO₂) and pulsed dye lasers (PDL) are instrumental in managing hypertrophic and keloid scars [13]. The use of 1064-nm Nd:YAG lasers targets the vascular component of scars, effectively reducing localized inflammation and hypoxia — factors critical in the pathogenesis of excessive fibrosis [25,26]. Thermal management often integrates with physical tension-reduction strategies; implementation of steroid tape and silicone fixation helps to counteract mechanotransduction [25,27].

The clinical validation of these interventions relies on standardized scoring systems such as the Vancouver Scar Scale (VSS) and its modified version (mVSS), which assess parameters including vascularity, height, pliability, and pigmentation [9,28]. Studies show that higher mVSS scores are significantly linked to a decrease in the quality of life for burn survivors [28]. Modern clinical trials also incorporate the SCAR-Q assessment, a validated patient-reported outcome instrument allowing comprehensive evaluation of the psychosocial impact of scarring, including symptoms, appearance, and quality of life [29,28].

Isolation Technologies: Enzymatic Digestion and Mechanical Micronization

As the clinical demand for adipose-derived therapies grows, the methodology of cell isolation has become a critical central point, directly impacting the cellular yield, viability, and regulatory classification of the final product. Historically, the "gold standard" for isolating ADSCs has been enzymatic digestion, a process primarily utilizing collagenase to chemically dissociate the extracellular matrix and release a concentrated population of cells known as the Stromal Vascular Fraction (SVF) [14,19]. While this method provides a high density of pure ADSCs, it is often restricted by stringent regulatory frameworks due to the extensive manipulation involved and the potential for residual enzyme contamination [14,30].

Recent advancements have prioritized mechanical micronization techniques offering a "minimal manipulation" alternative. One of the most significant developments is the production of nanofat and SVF-gel [16,31]. Nanofat is produced through a standardized mechanical shuffling process between syringes followed by fine filtration, effectively removing mature adipocytes while preserving the essential SVF cells and the microenvironment of the connective tissue matrix [16,32]. While non-enzymatic methods may produce a lower absolute number of cells than enzymatic digestion, the resulting product maintains a highly favorable immunophenotype and a rich secretome, making it an efficient and safer alternative for immediate "point-of-care" clinical use [30,33].

For Cell-Assisted Lipotransfer (CAL) — the enrichment of standard fat grafts with isolated SVF or ADSCs — the technique has shown superior volumetric retention in breast reconstruction and aesthetic augmentation by promoting early vascularization and reducing fat resorption [34,33,35]. In cases where the main goal is tissue rejuvenation rather than volume restoration, such as treatment of hypertrophic scars or facial atrophy in Parry-Romberg syndrome, mechanically derived products like SVF-gel or nanofat are preferred due to their high concentration of pro-regenerative cytokines and ease of intradermal injection [31,32,36].

The Biology of Exosomes and "Cell-Free" Therapy

A major reorientation in medical practice toward "cell-free" therapy is predicated on the utilization of exosomes as bioactive shuttles that replicate the regenerative effects of their parent stem cells without the associated risks of living cell transplantation. These nanosized extracellular vesicles, typically measuring between 30 and 150 nm, function as the primary currency of paracrine signaling, enabling intercellular communication by delivering a specialized cargo of proteins and nucleic acids to recipient cells [5,7,10,37]. Unlike traditional MSC therapy, exosomal interventions offer superior stability, reduced immunogenicity, and easier standardization for clinical dosage, effectively bypassing concerns regarding tumorigenicity or low survival rates of transplanted cells in the pathological microenvironment of a chronic wound [15,38,39].

The therapeutic potency of these vesicles is largely derived from their high concentration of non-coding RNAs, specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which act as the regulatory templates of tissue regeneration [4,10]. Within the context of ADSC exosomes, miR-125a-3p and miR-125b-5p have been identified as critical mediators that promote angiogenesis by targeting PTEN, while miR-31-5p enhances the migration of keratinocytes and vascular endothelial cells to accelerate re-epithelialization [10,38].

Adipose tissue is increasingly regarded as the optimal source for clinical regenerative applications. ADSCs are significantly more prevalent than their bone marrow counterparts, providing a cell yield nearly 500 times higher per gram of tissue [5,10]. Furthermore, ADSCs exhibit a more robust proliferative capacity and higher genetic stability in culture compared to BMSCs, which are often limited by donor age and lower metabolic activity [5,14]. Comparative studies suggest that ADSC-derived exosomes possess a unique secretome that is particularly effective in modulating macrophage polarization and enhancing the angiogenic response in diabetic and ischemic wound models [10,1,38]. Table 2 summarizes the comparative features and clinical limitations of these adipose-derived therapies.

Specialized Applications: From Facial Rejuvenation to Trichology

The multifaceted clinical applicability of adipose-derived therapies is particularly relevant in addressing the complex pathophysiology of Diabetic Foot Ulcers (DFUs). By delivering a molecular repertoire of angiogenic factors such as VEGF and HGF, adipose-derived therapies facilitate the transition from a dormant state to active granulation, significantly reducing amputation risks [18,42,15].

The therapeutic reach of adipose-derived products has also expanded into neurology, specifically targeting Alzheimer's and Parkinson's disease [15]. Exosomes represent a groundbreaking therapeutic agent due to their unique ability to cross the blood-brain barrier (BBB) and serve as targeted delivery systems. In Parkinson's disease models, exosome-mediated delivery of neurotrophic factors provides secretome-driven neuronal preservation for dopaminergic neurons, while in Alzheimer's disease, it assists in the clearance of amyloid-beta plaques [15,21].

This biological versatility is also employed in trichology, where the hair follicle microenvironment is revitalized through intricate paracrine signaling cascades. ADSCs revitalize the dermal papilla by delivering growth factors that trigger the telogen-to-anagen transition [17,21]. Autologous ADSC therapy for female pattern hair loss resulted in a markedly more prevalent increase in hair density and shaft diameter compared to traditional platelet-rich plasma (PRP) treatments [17,23,43].

In regenerative aesthetics, nanofat and SVF-gel enable precise intradermal delivery via high-gauge hypodermic instrumentation, stimulating the local microenvironment to induce neocollagenesis and effectively treating delicate indications such as perioral rhytids and infraorbital hyperpigmentation [22,32,36].

Reconstructive Challenges: Oncological Safety, Radiotherapy, and Breast Augmentation

The application of adipose-derived therapies in breast reconstruction requires rigorous reconciliation of regenerative potential with oncological surveillance. Post-mastectomy radiotherapy often precipitates significant tissue morbidity characterized by chronic inflammation and radiation-induced fibrosis (RIF). Irradiated tissue presents a particularly adverse microenvironment for standard fat grafting, typically resulting in suboptimal volume retention and compromised aesthetic outcomes [20,45].

To overcome these limitations, Cell-Assisted Lipotransfer (CAL) — enrichment of fat grafts with a high concentration of autologous ADSCs — has emerged as a superior strategy. This approach leverages the ability of ADSCs to modulate the fibrotic secretome and stimulate neovascularization, effectively revitalizing the irradiated site [20,40]. However, a significant challenge remains the occurrence of localized liponecrosis, mediated by inadequate early-stage perfusion of the graft. Necrotic pockets may form when the metabolic demands of transplanted adipocytes exceed the developing vascular architecture, leading to oil cysts and subsequent dystrophic calcification that may create diagnostic dilemmas potentially indistinguishable from malignant lesions on follow-up imaging [40,46].

Surgical refinements such as CO₂ tissue preparation are increasingly utilized to mitigate these risks, enhancing tissue compliance and creating a more favorable framework for graft survival [41]. Regarding oncological safety, contemporary clinical data provide a reassuring perspective: the utilization of ADSC-enriched grafts within a non-active oncological setting does not inherently amplify the risk of locoregional recurrence [20,46].

DISCUSSION

The findings of this narrative review indicate that scar and wound management should be considered as a combination of established conventional methods and emerging regenerative approaches. Silicone therapy and laser treatment remain important components of clinical practice, particularly in scar prevention, early hypertrophic scar management and postoperative scar remodelling [9,13,25,27]. Silicone therapy mainly acts through hydration of the scar surface and modulation of fibroblast activity, whereas laser treatment may reduce vascularity, influence local inflammation and support collagen remodelling [9,13,24–26].

Regenerative methods based on adipose tissue have expanded the therapeutic perspective from mechanical scar improvement toward biological modulation of tissue repair. Nanofat, stromal vascular fraction and ADSC-derived exosomes may influence wound healing through paracrine signaling, modulation of inflammation, stimulation of angiogenesis, improvement of microcirculation and remodelling of the extracellular matrix [10,14,16,19,22,31,44]. These mechanisms are particularly relevant in chronic wounds, diabetic foot ulcers, radiation-induced fibrosis, posttraumatic scarring and selected reconstructive indications [1,10,20,24,42].

The available evidence suggests that regenerative methods may be useful as complementary strategies in selected clinical situations. Conventional therapies remain more standardized in daily clinical practice, whereas adipose-derived and cell-free approaches are still characterized by variability in preparation protocols, biological composition, route of administration and outcome assessment [14,19,30,33,44]. Exosome-based therapies are of particular interest because they may reproduce part of the paracrine activity of stem cells without direct transplantation of living cells, with potential advantages including immunomodulatory activity, stimulation of angiogenesis and possible reduction of inflammatory persistence [4,5,7,10,15,38]. However, clinical translation remains limited by insufficient standardization, unclear dose definitions, limited comparative clinical evidence and the need for longer safety follow-up [15,38].

Safety remains an important issue. Available data from reconstructive applications are generally reassuring, but complications such as liponecrosis, dystrophic calcification and diagnostic uncertainty during imaging control remain clinically relevant [20,35,40,46]. The main limitations of current evidence include heterogeneity of protocols, variability of biological products, limited standardization of clinical indications, insufficient long-term follow-up and the absence of uniform outcome measures across studies [15,19,30,38,44].

CONCLUSIONS

Scar and wound management requires an integrated approach that combines conventional methods with modern regenerative strategies. Silicone therapy and laser treatment remain important methods for scar prevention and remodelling, particularly in the early management of hypertrophic scars and postoperative scarring. Their effects are mainly associated with hydration, modulation of fibroblast activity, targeting of the vascular component of the scar, and collagen remodelling.

Adipose-derived methods, including nanofat, stromal vascular fraction, and ADSC-derived exosomes, represent a promising direction in the treatment of chronic wounds, pathological scarring, soft tissue defects, and selected reconstructive conditions. Their potential effects are mainly related to paracrine regulation, modulation of inflammation, stimulation of angiogenesis, improvement of microcirculation, and remodelling of the extracellular matrix. These mechanisms are particularly important in conditions associated with impaired normal healing, including chronic wounds, diabetic foot ulcers, posttraumatic scarring, and postoperative scar changes.

At the same time, the clinical evidence differs between methods. Conventional approaches have broader clinical use and are more often assessed with standardized scar assessment scales, whereas adipose-derived methods and exosome-based approaches still require stronger comparative clinical data, standardized preparation protocols, clear safety monitoring, and longer follow-up. The main limitations include protocol heterogeneity, regulatory uncertainty, variability of biological products, and insufficient long-term safety data. Until such data are available, these methods should be regarded as promising, but not yet fully standardized treatment options.

DISCLOSURE

Author Contributions

Both authors contributed substantially to the conception and design of the review, literature analysis and interpretation, drafting and critical revision of the manuscript, and approved the final version for publication.

Conceptualization and methodology: Rafal Žuromskij.

Literature review and data selection, analysis and extraction: Rafal Žuromskij, Anastasiia Polishchuk.

Writing – original draft preparation: Rafal Žuromskij, Anastasiia Polishchuk.

Review and editing: Rafal Žuromskij, Anastasiia Polishchuk.

Conflict of Interest

The authors of this paper report no conflicts of interest.

Funding

The study did not receive specific funding.

Use of AI

Artificial intelligence tools were used solely to assist with vocabulary refinement and language editing. All conceptual decisions, including study design, data interpretation, references, scientific statements and final approval of the manuscript, were made independently by the authors to ensure the integrity and originality of the work. Authors are fully responsible for the content.

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