Aspects of the Pathogenesis of Skin Complications in the Stump-Prosthesis System in Dynamics: The Role of Bacterial and Mycological Dysbiosis

1. Introduction

Lim amputations result in serious physical disabilities that impair the quality of life for many people worldwide. The World Health Organization estimates that there are approximately 40 million amputees worldwide [1]. This number is expected to grow due to increased life expectancy and, consequently, higher risks of injury, as well as a high incidence of diabetes and vascular disease.

Rehabilitation of patients after limb amputation remains one of the most complex and pressing challenges in modern medicine. While prosthetic devices can restore mobility and improve quality of life, prolonged contact of the stump skin with the materials of the socket creates extreme conditions for the skin’s function.

Prolonged tissue contact with the socket triggers a cascade of microbiotic changes, the nature of which changes dramatically over time. In the first 12 months after amputation, primary adaptation occurs, accompanied by mechanical stress, maceration, and a dramatic restructuring of the microbiome. Between 12 and 24 months, relative compensation develops, but persistent dysbiosis often leads to latent inflammation and the formation of resistant bacterial biofilms. After 24 months, chronic degenerative skin changes and profound infectious complications due to the depletion of local defense mechanisms become more prominent.

Local temperature increases, occlusion, constant friction, and maceration inevitably lead to disruption of the skin’s barrier function. Under these conditions, a dramatic restructuring of the microbiome occurs: resident microflora is suppressed and opportunistic strains are activated.

The publication selection process was conducted by independent researchers in three stages: title screening, abstract analysis, and final assessment of full-text versions for inclusion/exclusion criteria.

This literature review analyzes aspects of the pathogenesis of skin lesions in the stump-prosthesis system at different stages of prosthesis wear, as well as assessing the effectiveness of existing methods for correcting dysbiosis, taking into account the length of prosthesis wear.

2. Materials and Methods

This work is a critical narrative review with a matrix-oriented evidence synthesis (structured evidence mapping).

Scale for the Assessment of Narrative Review Articles (SANRA) principles were used to quality control the narrative review: justification of the importance of the topic and objectives; reproducible search description; correct citation; and explicit presentation of the level of evidence and endpoints. A systematic review format with a PRISMA diagram was not used due to the fundamental heterogeneity of the primary studies: differences in matrices, probe panels, designs (retro-/prospective series, pilot studies, R&D work), and comparator methods preclude a valid meta-analytic synthesis. This rationale is consistent with the logic of applying SANRA to narrative reviews; PRISMA is considered the standard for systematic reviews, therefore, PRISMA flow was not used in this work [2,3].

A targeted search was conducted in PubMed and Scopus databases. Search dates ranged from the database creation date in January 1980 to May 2026. Reference lists of key articles were also reviewed. Search terms included: “mechanical skin complications from prosthesis wearing”, “inflammatory and allergic skin complications from prosthesis wearing”, “infectious complications of the skin and subcutaneous fat”, “changes in the skin bacteriome of the stump”, and “changes in the skin mycobiota of the stump”.

Clinical scenarios/matrices: amputation stump (residual limb), skin dysbiosis (skin dysbiosis), skin mycobiota (fungal shift), prosthetic liner (interface), chronic wound (wound healing).

The publication selection process was conducted by independent researchers in three stages: title screening, abstract analysis, and final assessment of full-text versions for inclusion/exclusion criteria.

Publications meeting the following mandatory parameters were selected for the final literature pool: original peer-reviewed studies (clinical, cohort, randomized controlled, cross-sectional), case series with in-depth laboratory analysis, as well as fundamental reviews (narrative and systematic reviews) and meta-analyses; patients with lower extremity amputations (at any level: lower leg, thigh, foot) using exoprostheses with various types of sockets and interfaces (silicone, polyurethane, copolymer liners); works studying the pathophysiology of the stump skin, changes in the microbiome (bacteriome) and mycobiota under the influence of occlusion, friction, and pressure; Studies of molecular markers of inflammation (cytokines, IL-23/IL-17 axes) and mechanisms of biofilm formation on prosthetic materials.

Articles were consistently excluded from the analysis and citation process if they met at least one of the following criteria: purely experimental studies without a clinically relevant matrix; publications that used skin reactions from wearing a prosthesis solely as a research marker without a described diagnostic logic and potential for transfer to a clinical review.

3. Results

3.1. Mechanical Skin Complications from Wearing a Prosthesi

Biomechanical and thermophysical factors act synergistically during prosthesis wear, preparing the substrate for degradation of the skin microbiome. Constant cyclic friction/tissue displacement, including that of the liner, and daily fluctuations in stump volume, combined with peak pressure on bony protrusions, lead to changes in the skin of the stump.

Clearly, the shape of the prosthetic socket and the materials used are of primary importance in the development of mechanical damage to the skin. Skin abrasions and maceration occur due to hyperhidrosis within the confined space of the liner/sleeve. Constant moisture reduces the barrier properties of the epidermis, leading to desquamation of the stratum corneum due to friction. Mechanical complications arising from the skin and soft tissues of the stump when interacting with the prosthetic socket can be compared to the following time periods (Table 1).

In the pathogenesis of skin complications, three time intervals are clearly differentiated, characterized by a natural change from acute traumatic and irritative processes to chronic proliferative, degenerative and deep infectious lesions.

3.1.1. The Period of up to 12 Months (Primary Adaptation)

It is characterized by an intense reduction in the volume of the soft tissues of the stump (post-traumatic atrophy, edema). This often leads to a discrepancy between the contours of the stump and the socket (play), causing specific mechanical damage [11,12]: linear abrasions and superficial erosions are localized in areas of greatest shear stress when walking (proximal edge of the socket, area of bony protrusions) [13]; marginal and distal edema develops as a result of the “piston” effect when the stump is not tightly fitted, which disrupts venous and lymphatic outflow [14]; superficial ischemic ulcers form at areas of peak point pressure (for example, over the head of the fibula or the end of the bone cut), where the sleeve compresses small capillaries [15,16].

3.1.2. Period from 12 to 24 Months (Volume Stabilization Stage)

It is characterized by stabilization of the stump architecture, however, ongoing cyclic microtrauma and friction can change the structure of the skin [17]: lichenification and hyperkeratosis as a protective thickening of the stratum corneum in areas of constant mechanical pressure (the skin becomes hard, dense, and begins to peel) [18]; calluses (skin calluses) and deep cracks appear due to a lack of elasticity in local areas of the skin under shear loads [19]; chronic deep ulcers (mechanical pressure ulcers) at points of constant contact with fastening elements or deformed walls of the seat [20]; intradermal hemorrhages (petechiae, ecchymosis) are caused by rupture of superficial capillaries under the influence of vacuum (suction) suspension systems when the prosthesis is displaced [21].

3.1.3. A Period of More than 24 Months (Stage of Remote Changes)

It is associated with the development of persistent structural changes in tissues caused by long-term hypoxia, soft tissue fibrosis and wear/deformation of the socket (when wearing an “unadapted” prosthesis) [22,23]: skin growth in the form of wart-like outgrowths at the distal end of the stump (warty epidermal hyperplasia). This occurs due to the lack of complete skin contact with the base of the socket (the so-called “strangulation effect” of the stump) [24]; acroangiodermatitis (Kaposi’s pseudosarcoma) manifests as purple-blue plaques and dense infiltrates. It results from severe chronic venous congestion and microcirculatory dysfunction due to abnormal pressure distribution within the socket [25]; trophic ulcers of scar tissue, if postoperative scars are fused with the underlying bone. This occurs due to complete loss of skin mobility and progressive ischemic necrosis under stress [26,27]; formation of subcutaneous synovial sacs – the formation of fluid-filled cavities in areas of greatest skin friction against the rigid edges of the prosthesis [28,29].

3.2. Inflammatory and Allergic Skin Complications from Wearing a Prosthesis

Along with mechanical tissue decompensation, inflammatory and allergic skin complications occupy a leading place in the structure of stump-prosthesis interface pathologies. Their pathogenesis is intermittent and complex, with primary physicochemical triggers closely intertwined with immunological and microbiological changes (Table 2).

3.2.1. Period up to 12 Months (Primary Sensitization Stage)

During the first year of use, acute inflammatory reactions caused by occlusion (closed environment), impaired thermoregulation and direct chemical irritation predominate [40]: simple irritant contact dermatitis occurs in the first few months due to the retention of sweat and salts under the liner. It manifests as localized erythema (redness), itching, and burning. [41]; superficial candidiasis (intertrigo) develops in conditions of high humidity and epidermal maceration. Yeast-like fungi infect the skin folds and the distal end of the stump, causing oozing and a white coating [42,43]; acute folliculitis and ostiofolliculitis (inflammation of the hair follicles) are caused by mechanical blockage of the sebaceous gland openings and the proliferation of Staphylococcus spp. Characterized by the appearance of small pustules (pustules) [44]; contact urticaria (an acute, immediate-type allergic reaction). It occurs within a few hours or days after contact with latex or unstabilized polymers. It manifests as blisters and severe swelling [45].

3.2.2. The Period from 12 to 24 Months (The Stage of Subacute Progression and the Appearance of Delayed-Type Allergic Reactions)

By this period, the latent period necessary for the formation of a specific T-cell immune response (sensitization) to the components of the prosthesis materials is completed [46]: allergic contact dermatitis: A specific, delayed-type reaction. It is triggered by additives used in the production of sleeves and liners: rubber vulcanization accelerators (thiourams), plasticizers, epoxy resins, dyes, or nickel. It is characterized by eczematous rashes that extend beyond the area of direct contact [47]; toxicoderma due to the action of exogenous detergents - inflammation caused by the cumulative effect of chemical residues of soap or disinfectants that are not properly washed out of the pores of the liner during daily care [48]; chronic furunculosis is the development of deep inflammation of the hair follicles and surrounding tissues with the formation of a necrotic core caused by staphylococcal infection. It occurs due to a persistent decrease in local skin immunity under conditions of constant ischemia and occlusion [49].

3.2.3. A Period of More than 24 Months (The Stage of Chronic Proliferative-Inflammatory Reactions)

With prolonged wearing of the prosthesis (over two years), deep structural changes in the skin develop, associated with chronic inflammation and tissue degeneration [50]: microbial and true eczema of the stump (chronic recurrent inflammation). The skin thickens, becomes covered with dry crusts, plaques, and deep, painful cracks due to years of sensitization and constant inflammation [51]; late (time-induced) allergic dermatitis develops after several years of undisturbed wear due to the gradual aging, degradation, and hydrolysis of the liner’s polymers. Released plastic monomers begin to penetrate deep into the thinned epidermis [52]; epidermoid cysts (atheromas) in friction zones are benign, hollow formations filled with sebum and keratin. They form due to chronic inflammation and mechanical insertion of epidermal cells into the dermis along the edges of the prosthesis. They are often subject to secondary suppuration [53].

3.3. Infectious Complications of the Skin and Subcutaneous Fat from Wearing a Prosthesis

Infectious complications in the stump-prosthesis system are the result of critical damage to the anatomical barriers of the skin in combination with local immunodeficiency [11,13]. Constant mechanical pressure, shear stress, epidermal maceration by sweat, and the cumulative toxic effects of detergents destroy the stratum corneum and lipid layer of the skin stump. Under conditions of tissue ischemia and hypoxia caused by capillary compression by a rigid sleeve, local resistance is sharply reduced: macrophage phagocytic activity is inhibited, leukocyte chemotaxis is slowed, and the synthesis of endogenous antimicrobial peptides (defensins) is blocked [13] (Table 3).

3.3.1. Period up to 12 Months (Stage of Manifestation of Superficial Opportunistic Infection)

The first year is characterized by acute infections of the epidermis and hair follicles, developing against the background of skin maceration, excess moisture (hyperhidrosis) and primary colonization of the skin by pathogens [63]: superficial pyoderma (ostiofolliculitis, folliculitis) is a bacterial infection of the hair follicle openings, caused primarily by Staphylococcus aureus. It manifests as multiple small pustules with an erythematous rim in areas of greatest friction. [64]; streptococcal impetigo is a contagious superficial infection caused by Streptococcus pyogenes. It is characterized by the rapid formation of thin-walled blisters, which develop into typical, layered, honey-yellow crusts [65].

3.3.2. Period from 12 to 24 Months (Stage of Invasive and Deep Bacterial Infection)

In the second year of prosthesis use, deep lesions of the dermis and hypodermis become more prominent. This is due to the penetration of microorganisms through microcracks, ulcers, and hyperkeratotic zones formed during chronic mechanical trauma [66]: furuncles and carbuncles are acute purulent-necrotic inflammation of the hair follicles and surrounding subcutaneous tissue, with the formation of dense infiltrates and necrotic rods. They occur due to deep penetration of staphylococcal infection [67]; erysipelas of the stump (erythematous or bullous form) is a clearly demarcated acute infectious lesion of the skin caused by group A beta-hemolytic streptococcus. It develops against the background of defects in the skin barrier and concomitant lymphostasis (edema) of the stump [68]; bacterial cellulitis (subcutaneous cellulitis) is a diffuse purulent inflammation of soft tissues without clear boundaries. It is caused by mixed microflora (Staphylococcus spp., Streptococcus spp.) during infection of deep calluses and cracks [69].

3.3.3. Period Longer than 24 Months (Stage of Chronic, Biofilm-Associated, Specific Infection)

With prolonged prosthesis wear (over two years), resistant infections may develop. Pathogens form persistent biofilms on porous and degraded liner/socket materials, and the stump tissues undergo profound ischemic degeneration [70]: chronic ulcerative pyoderma – long-term non-healing infected ulcers (bedsores) colonized by associations of multidrug-resistant strains (including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus). Accompanied by a putrid odor and flaccid granulation [71]; hidradenitis suppurativa is a chronic inflammation of the apocrine sweat glands in the proximal areas adjacent to the edges of the sleeve (e.g., in the groin or axillary region). It is characterized by the formation of painful nodules, fistulas, and scars due to persistent mechanical obstruction of the excretory ducts and secondary infection [72].

3.4. Changes in the Skin Bacteriome of the Stump When Wearing a Prosthesis

Wearing a prosthesis (especially removable limb prostheses that contact the stump) fundamentally alters the physical and chemical conditions in the contact area. This causes the development of specific local dysbiosis [73].

The prosthesis creates a closed chamber under the socket with increased humidity, temperature, and occlusion. This suppresses resident flora and stimulates the emergence of transient flora [74]: declining alpha diversity: the total number of bacterial species decreases. A few dominant pathogens predominate [75]; commensal suppression: the proportion of lipophilic bacteria Cutibacterium acnes decreases [76], dry zones of Micrococcus and protective strains of Staphylococcus epidermidis [77]; growth of facultative and obligate anaerobes: under hypoxic conditions under the sleeve, the population of gram-negative bacteria (P. aeruginosa, Proteus mirabilis, Enterobacteriaceae) increases sharply [78]; the colonization density of S. aureus increases sharply. They displace coagulase-negative staphylococci. [79].

Diagnosis and monitoring of skin dysbiosis under the prosthesis are based on the following measurable parameters: the presence of a matrix of extracellular polymers formed by polymicrobial biofilms on the skin surface and polymeric materials of the prosthesis, which protects bacteria from antiseptics [80]; the indicator shifts from slightly acidic (normal: 4.7–5.5) to neutral or alkaline (>6.5) due to the release of bacterial metabolites (ammonia) [81]; S. aureus/S. epidermidis ratio: a biomarker of barrier degradation. The higher the ratio, the more severe the inflammation [82]; increased levels of proinflammatory cytokines: in tissues and exudate, concentrations of IL-1β, TNF-α and IL-8 induced by lipopolysaccharides (LPS) of gram-negative flora significantly increase [83].

The skin of the shin or thigh is histologically not designed to bear weight-bearing loads (unlike the plantar skin of the sole). Constant friction and vertical pressure from the prosthesis sleeve lead to micro-tears in the stratum corneum. Under occlusion and moisture conditions, this barrier damage does not have time to regenerate, turning into erosions. An altered, depleted microbiome (dysbiosis) immediately colonizes these defects, transforming a mechanical wound into an infected pathological ulcer. Dysbiosis directly blocks the normal phases of the wound healing process [84]: S. aureus and P. aeruginosa secrete endotoxins and exoenzymes that continuously activate macrophages. The wound becomes stuck in the inflammatory phase, not progressing to proliferation [85]; pathogen toxins suppress keratinocyte migration and proliferation. Normally, this process is stimulated by signals from the commensal S. epidermidis (via toll-like receptors 2 (TLR2); in dysbiosis, this mechanism is disabled) [86]; biofilms impair local hemodynamics. They block the production of vascular endothelial growth factor (VEGF), stopping the formation of new capillaries in granulation tissue (impaired angiogenesis) [87]; bacterial proteases destroy collagen and fibronectin faster than cells can synthesize them. This leads to chronic skin defects due to the degradation of the extracellular matrix [88].

3.5. Changes in the Mycobiota of the Skin of the Stump When Wearing a Prosthesis

Conditions inside the prosthesis socket dramatically alter the skin’s microenvironment, transforming it into a closed ecosystem. Constant occlusion, the greenhouse effect (excessive heat and 100% humidity), the accumulation of sebum lipids, and maceration (softening) of the stratum corneum (stratum corneum) disrupt the natural protective barrier. These destructive factors trigger profound qualitative and quantitative changes in the local microbiome. This transformation affects not only the bacterial community (bacteriome) but also the fungal component of the resident flora – the mycobiota.

Normally, the skin mycobiota consists of approximately 80–90% lipophilic yeasts of the genus Malassezia [89]. Wearing a prosthesis shifts this balance. The authors noted several characteristics: chronic interdigital/interfingered trichophytosis and ulcerative candidiasis – a sluggish fungal infection resistant to standard therapy due to deep mycotic involvement of macerated and scarred tissue [90]; maceration of the skin (softening from sweat) provokes excessive growth of yeast-like fungi of the genus Candida and diffuse proliferation of Malassezia (fungal shift) [91]; superficial mycosis (dermatophytosis and candidiasis of the stump) is a fungal infection caused by Candida albicans or dermatophytes (Trichophyton spp.). It develops in the distal areas and natural folds of the skin due to the greenhouse effect within the liner. It is characterized by oozing, itching, and detachment of the stratum corneum [92].

Against this backdrop, an even greater shift in species composition occurs. Commensal species (Malassezia restricta, Malassezia globosa) are replaced by species associated with inflammatory processes (e.g., Malassezia furfur), which activate lipase synthesis in response to excess sebum and sweat.

The tissues of lower limb stumps after amputation always exhibit cicatricial changes and microcirculatory disturbances (ischemia, vascular sclerosis, venous and lymphatic stasis). Scar tissue lacks a normal capillary network, so local immunity (macrophages, T-lymphocytes) and systemic antifungal agents (fluconazole, itraconazole) circulating in the blood simply cannot reach the mycotic lesion in therapeutic concentrations. A chronic ulcer develops that is indolent and resistant to standard treatment [93].

In addition to a change in the dominant pathobiont (Malassezi), there is a sharp increase in the population of opportunistic yeast-like fungi of the genus Candida (primarily C. albicans, less commonly Candida parapsilosis and Candida tropicalis). Normally, their presence on the skin of the extremities is minimal [94]. Under conditions of constant maceration of the epidermis, the abnormal appearance of dermatophytes (Trichophyton, Microsporum, Epidermophyton genera) and non-dermatophyte mold fungi (Aspergillus spp., Fusarium spp.) is recorded on the skin of the stump [95].

C. albicans dimorphism is a classic visual and genetic marker of virulence. Normally, C. albicans exists on the skin as round, single-celled blastospores (yeast phase), which are easily washed away and controlled by the immune system. Under the skin liner, triggers – elevated temperature (37°C), hypoxia, high CO2 levels, and neutral pH (alkalization by ammonia) – activate transcription factors (such as Efg1 and Cph1). The cell begins to rapidly elongate, first forming germ tubes and then true hyphal mycelium. Hyphae express adhesin proteins (the Als family, especially Als3) on their surface, which tightly bind to cadherins of keratinocytes. Due to directed growth and turgor pressure of the hyphal tip, the fungus literally “pierces” and pushes apart the macerated corneocytes, penetrating the dermis. In other words, Candida is a marker of the transition from colonization to invasion. It is detected microscopically by the transition of round blastospores (yeast form) into filamentous forms – pseudomycelium and true mycelium – which are capable of penetrating the stratum corneum. [96]; the secretion of acidic proteases (SAP) and phospholipases can serve as a biochemical marker of fungal aggression. Fungi of the genus Candida and Malassezia actively secrete these enzymes for the destruction of keratinocytes and skin lipids under the sleeve [97]; the formation of mixed bacterial-fungal biofilms can be called a structural marker. Fungal mycelium serves as a framework on which bacteria (for example, S. aureus) are attached, forming an extracellular matrix resistant to antifungals [98]; a sharp increase in the levels of interleukins IL-17 and IL-23 is recorded in skin biopsies and wound exudate. This is a specific immune response of macrophages and T-helpers type 17 to fungal cell walls (β-glucans and mannans) [99].

4. Discussion

The results of the analysis indicate that the skin of a lower limb amputation stump, when used with prosthetic and orthopedic devices, is exposed to the aggressive combined effects of biomechanical and microecological factors. The formation of a closed space under the prosthetic socket (particularly when using silicone or polyurethane liners) dramatically alters the physiology of the skin. The greenhouse effect, characterized by local hyperthermia (36–37°C) and often 100% humidity, combined with the accumulation of sebum lipids and persistent maceration of the epidermis, acts as a primary trigger for profound qualitative and quantitative changes in the local microbiome. The systemic dysbiosis and tissue decompensation in the stump-prosthesis circuit involve several sequential steps (Scheme 1):

I. Trigger initiation phase. A rigid sleeve can act as an inducer of microcirculatory collapse. Shear stress mechanically disrupts the dermal-epidermal junction, and sweat acts as a natural hydrolytic breaker of keratinocyte tight junctions.

II. Ischemia switches tissue metabolism to hypoxic stress. The most important pathogenetic marker here is the suppression of β-defensin synthesis. The skin of the stump loses its ability to resist uncontrolled colonization by microorganisms.

III. Under the thermostatic conditions of the sleeve (humidity, occlusion), a dysbiotic shift occurs. Bacteria and fungi exert combined adhesion not only on the skin but also on the porous structure of silicone or polyurethane liners. This leads to biofilm formation—the formation of conglomerates protected by an exopolysaccharide matrix and resistant to the host immune response.

IV. Biofilm waste products activate antigen-presenting cells, triggering the interleukin cascade. IL-17 expression stimulates uncontrolled keratinocyte mitosis and neutrophil chemotaxis. Since pathogen evacuation is impossible due to the presence of biofilms on the prosthesis, the circuit is locked into a vicious cycle of chronic inflammation.

V. The result is staged skin destruction. The process evolves from initial superficial erosions and ostiofolliculitis, through a stage of sensitization and deep bacterial invasions such as erysipelas and cellulitis, to the final destructive remodeling of the matrix. In the later stages (over 24 months), atypical angiogenesis in response to constant hypoxia (acroangiodermatitis) and vegetative tissue growths (warty hyperplasia) predominate.

The observed alkalization of the microenvironment (a shift in pH from the slightly acidic normal range of pH 4.7–5.5 to neutral and alkaline values pH >6.5–7.0) is pathogenetically determined by the metabolic activity of urease-positive transient flora. The breakdown of urea in exocrine sweat by bacterial urease, releasing free ammonia (NH3) and the subsequent formation of ammonium hydroxide (NH4OH), not only destroys the protective “Marchionini acid mantle” but also activates the host’s endogenous serine proteases (kallikreins). This leads to degradation of corneodesmosomes, exacerbating maceration and paving the way for microbial invasion due to constant friction from the prosthesis sleeve.

Of particular interest is the observed shift from colonization with S. aureus to infection and the parallel transformation of the mycobiota (fungal component). Under normal conditions, up to 80–90% of the mycobiota of glabrous skin is represented by lipophilic yeasts of the genus Malassezia. However, in the destructive microenvironment of prosthetic tissue, their ecological monopoly is lost. The transition of opportunistic C. albicans fungi from the yeast phase (blastospores) to the mycelial invasive form (pseudohyphae and true mycelium) serves as a key phenotypic marker of aggression. This dimorphism, induced by hypoxia, excess CO2, and alkaline pH, is accompanied by the active secretion of phospholipases (primarily PLB) and SAPs 1–3, which directly lyse the membranes of fibroblasts and keratinocytes in granulation tissue. The abnormal involvement of non-dermatophyte mold fungi (Aspergillus spp., Fusarium spp.) in the infectious process emphasizes the extreme degree of degradation of the local tissue barrier, transferring the usual dermatitis of the stump into the plane of opportunistic deep mycosis.

The observed resistance of stump skin defects to standard antibacterial and antifungal therapy is explained by the formation of polymicrobial bacterial-fungal biofilms. A three-dimensional framework of fungal mycelial filaments serves as a physical scaffold for S. aureus adhesion (via ligand-receptor interactions between the fungal Als3 protein and the bacterial FnBPA). The co-synthesized extracellular polymer matrix, enriched with fungal β-1,3-glucans and bacterial exopolysaccharides, functions as a molecular sieve, shielding pathogens from the action of endogenous antimicrobial peptides and systemic antibiotics, contributing to the chronicity of ulcerative defects for months.

Molecular analysis of the mechanisms underlying delayed stump wound healing indicates a blockade of all phases of regeneration. First, the inflammatory phase persists: excess bacterial LPS from gram-negative bacteria (P. aeruginosa, P. mirabilis) and fungal β-glucans lead to hyperactivation of TLR-4 and TLR-2 receptors on resident macrophages. This induces excessive release of proinflammatory cytokines (IL-1β, TNF-α, IL-8) and triggers the IL-23/IL-17 axis, which recruits neutrophils. Large filaments of fungal mycelium, which cannot be ingested by phagocytes, trigger the development of a “frustrated phagocytosis” effect. In unsuccessful attempts to internalize the object, macrophages and neutrophils perform massive extracellular exocytosis of lysosomal enzymes and reactive oxygen species, causing collateral damage to healthy marginal tissues of the stump.

Secondly, proliferation and epithelialization processes are completely blocked. Microbial biofilms disrupt local hemodynamics and angiogenic shifts by selectively suppressing the expression of VEGF, which halts capillary ingrowth and the formation of adequate granulation tissue. Cell wall components of Candida spp. disrupt contact inhibition and polarized lamellipodial movement of keratinocytes along the wound edges, depriving them of stimulatory signals normally provided by the commensal S. epidermidis via the TLR-2 pathway. Third, combined proteolysis (the release of bacterial keratinases/collagenases and the induction of host neutrophil matrix metalloproteinases MMP-8 and MMP-9) leads to the rate of extracellular matrix destruction exceeding the synthetic activity of fibroblasts many times over.

Thus, the skin beneath the prosthesis socket forms a unique pathological biotope, where mechanical microtrauma, due to the synergistic effects of bacterial and mycotic dysbiosis, is transformed into a torpid, non-healing chronic ulcer. This necessitates a revision of standard protocols for the care of such patients and the implementation of preventive measures aimed at targeted correction of the mycobiota and biophysical parameters (pH, humidity) of the skin-liner interface.

5. Conclusions

The use of prosthetic and orthopedic devices (at the skin-liner interface) leads to a critical biophysical shift: the greenhouse effect and epidermal maceration due to the accumulation of moisture and sweat cause persistent alkalization of the environment (pH > 6.5). This process, catalyzed by the release of bacterial ammonia, disrupts the protective hydrolipid mantle and activates host kallikreins, causing degradation of corneodesmosomes and opening the gates for pathogen invasion due to biomechanical friction of the sleeve.

Prolonged occlusion and hypoxia provoke a large-scale mycological shift (fungal shift), characterized by the loss of ecological dominance of the resident commensal Malassezia spp. and the transition of the opportunistic yeast C. a albicans from the colonizing spore phase to the invasive mycelial form. The additional involvement of non-dermatophyte molds (Aspergillus spp., Fusarium spp.) in the stump biotope structure serves as a direct marker of profound tissue barrier destruction and local immunosuppression.

The formation of polymicrobial bacterial-mycotic biofilms under the stump, where fungal mycelial filaments serve as an adhesive framework for S. aureus, is a key factor in the resistance of stump infections to therapy. The co-synthesized extracellular polymer matrix (rich in β-1,3-glucans) effectively shields microbial associations from the effects of systemic antifungals, antibiotics, and endogenous antimicrobial peptides, prolonging the wound healing process. The chronicity of wound defects in the stump at the molecular level is caused by the development of the phenomenon of “frustrated phagocytosis”, in which macrophages and neutrophils, unable to internalize large filaments of fungal mycelium, continuously secrete reactive oxygen species and lysosomal enzymes into the environment. This blocks the shift of macrophages from the proinflammatory M1 phenotype to the regenerative M2, damaging healthy marginal tissues and perpetuating the wound in the persistent inflammatory phase.

Infection-related dysbiosis completely paralyzes proliferation and epithelialization processes in the stump tissue. Due to microbial toxins and proteolysis (bacterial keratinases and neutrophil metalloproteinases MMP-8/MMP-9), the rate of degradation of the extracellular matrix exceeds its synthesis by fibroblasts, and blocking the angiogenic factor VEGF and the TLR-2 signaling pathway stops the growth of capillaries and the directed migration of keratinocytes, which leads to the formation of torpid, non-healing ulcers.