Medical Microplastics: Research Progress on Exposure Pathways, Toxic Effects, and Detection Methods

Abstract

The escalating use of plastic medical products has made medical microplastics (MMPs) contamination an important health concern for specific populations (e.g., patients undergoing medical interventions) and has rendered it a growing focus in global environmental health research. This review systematically summarizes the release characteristics of MMPs throughout their life cycle from device manufacturing and clinical use to waste disposal, and elucidates human exposure pathways. For the general population, environmental exposure and dietary intake are the dominant exposure sources. In patients, however, invasive procedures and intravenous infusions serve as direct, high-concentration routes, enabling MMPs to enter the bloodstream directly. The article focuses on analyzing the molecular mechanisms underlying multisystem pathological effects induced by MMPs, including cardiovascular injury, respiratory dysfunction, digestive disorders, and reproductive toxicity, which involve key pathways such as oxidative stress, inflammatory responses, apoptosis, and dysregulated autophagy. Regarding existing detection technologies, we compare and evaluate the advantages and limitations of microscopic observation, spectral analysis, and chromatography–mass spectrometry in terms of sensitivity, specificity, and applicability, proposing that integrated technical strategies can significantly improve detection reliability. Finally, the review discusses current challenges and future research directions, including the establishment of standardized risk assessment frameworks, the development of highly sensitive in situ detection technologies, and the exploration of targeted intervention strategies. This work provides a theoretical basis for understanding the health risks of MMPs and offers valuable insights for formulating safety management policies for medical plastics.

1. Introduction

Microplastics (MPs), as emerging environmental contaminants, are typically defined as plastic particles smaller than 5 mm, characterized by their persistence, bioaccumulation potential, and inherent toxicity [1]. In recent years, the healthcare sector has been identified as a significant source of MPs, which are continuously released throughout the entire lifecycle of medical plastic products, including manufacturing [2], clinical application [3], and waste disposal [4]. Of particular concern are medical microplastics (MMPs), which possess distinct physicochemical properties [5]. This is partly because medical-grade plastics often contain additives such as plasticizers and stabilizers [6] and partly because healthcare-specific processes like sterilization and mechanical abrasion can alter the surface characteristics of MPs [7], potentially rendering them more bioactive than those originating from general environmental sources.

Epidemiological studies have documented the release of MMPs from medical scenarios such as dental procedures and traditional Chinese medicine decoction packaging [8,9], with invasive medical procedures representing a unique high-risk exposure pathway [10]. This unique exposure pathway results in a bioavailability significantly higher than that of MPs ingested orally [11]. Recent studies have detected markedly elevated concentrations of MPs, primarily polyamide (PA) and polyethylene (PE), in the bloodstream of patients following percutaneous coronary intervention (PCI) [12]. Furthermore, results from exposure assessment models have estimated the annual exposure to MPs per person via syringes, infusion sets, and venous indwelling needles at 3.75, 6.22, and 0.35 items, respectively [13]. Accordingly, the total annual exposure from these medical devices was calculated to be approximately 10.32 items, corresponding to a per capita daily exposure level of about 0.028 items.

Given the ubiquity of MMPs exposure and their potential health risks, this article systematically reviews recent advances from four key perspectives: source characteristics, environmental behavior, toxicological effects, and detection technologies. Specifically, it aims to: (1) elucidate the mechanisms of MMPs release during the production and use of medical plastic products; (2) analyze human exposure pathways to MMPs; (3) uncover the molecular pathways underlying MMPs-induced multi-organ toxicity; and (4) evaluate the applicability and limitations of existing detection techniques. Through interdisciplinary analysis, this review seeks to provide a scientific basis for establishing risk assessment frameworks and mitigation strategies for MMPs.

2. Methodology

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement to ensure transparency, reproducibility, and rigor [14]. The study selection process is summarized in Figure 1. The detailed methodology is described as follows.

2.1. Literature Search Strategy

A comprehensive and structured literature search was performed across four major academic databases to cover both English and Chinese research outputs: Web of Science, Scopus, PubMed (for English literature), and China National Knowledge Infrastructure (CNKI, for Chinese literature). The search time frame was restricted from January 2010 to December 24, 2025, to encompass foundational and the latest advances in the field of MMPs. The core search strategy combined subject terms and free-text terms to maximize sensitivity: (“medical microplastics” or “medical MPs”) and (“source” or “exposure pathway” or “toxicity” or “detection”). No restrictions were imposed on study types to comprehensively capture original research articles, reviews, and short communications, with the search language limited to English and Chinese. All retrieved records were imported into the EndNote reference management software [2024] for duplicate removal and subsequent screening. The core strategy was adapted for each database using appropriate field tags (e.g., Ti-tle/Abstract for PubMed, TS for Web of Science, TITLE-ABS-KEY for Scopus, and subject field for CNKI), with all searches limited to the specified date range and languages. For PRISMA checklist, see Supplementary Material.

2.2. Study Selection Criteria

Studies were included if they met the following criteria: (1) focused explicitly on MMPs originating from medical scenarios (e.g., medical device use, sterilization, waste disposal); (2) reported MMPs-related data on source characteristics, release mechanisms, exposure pathways, toxic effects, or detection methods; (3) contained original experimental, clinical, or mechanistic data, or were systematic reviews with clear conclusions (studies distinguishing MMPs from environmental microplastics were prioritized); and (4) were published as peer-reviewed journal articles or authoritative book chapters.

Studies were excluded if they: (1) solely investigated environmental MPs without a medical context; (2) lacked empirical data (e.g., theoretical speculations, commentaries, or data-free reviews); (3) were non-standard publications (e.g., conference abstracts, preprints, duplicates); or (4) had inaccessible full texts or missing key experimental parameters.

2.3. Study Selection Process

Database searches identified 630 records. After removing 99 duplicates, 531 records were screened. Based on title/abstract, 396 were excluded. Full texts of 135 reports were retrieved and assessed; 13 were excluded (irrelevant topic: 7; inaccessible full text: 4; others: 2). Finally, 122 studies were included.

2.4. Data Extraction and Synthesis

Data from the 122 included studies were independently extracted by two reviewers using a standardized form, covering variables such as MMPs source, polymer type, particle characteristics, exposure routes, toxic effects, molecular mechanisms, and detection methods. Disagreements between the two reviewers were resolved through discussion or by consulting a third reviewer. Data were synthesized into tables and figures for comparative analysis.

2.5. Methodological Notes

Screening and eligibility were assessed independently by two reviewers, with discrepancies resolved by a third. No formal quality appraisal or meta-analysis was performed due to the scoping review design and methodological heterogeneity across studies.

3. Sources and Classification Characteristics of MMPs

3.1. Release Mechanisms of MMPs in Healthcare Environments

In the healthcare sector, plastic products are extensively utilized in various medical devices and consumables [15], primarily employing three types of polymers: PE, polypropylene (PP), and poly (vinyl chloride) (PVC) [16]. Figure 2 illustrates the potential pathways for MMPs generation from relevant material products in high-intensity, dynamic surgical environments. Disposable gloves [17] release flake- or fiber-like MMPs due to surface abrasion and localized ruptures caused by frequent manipulation, contact with sharp instruments, and liquid immersion. Syringes [18] shed MMPs through repeated aspiration and high-pressure injections, via reciprocating friction between the piston and barrel wall, stress concentration at the needle hub connection, and fluid scouring effects. Blood transfusion bags [19] release MMPs via fluid dynamic effects and material fatigue mechanisms resulting from tubing compression and bending, pressure fluctuations during rapid infusion, and temperature variations. These pathways often occur simultaneously or successively, thereby forming composite sources of MPs exposure in medical settings.

Collectively, MPs generated from these medical devices, along with the plastic waste itself, ultimately enter environmental systems. Inadequate management of MMPs pollution may exacerbate the accumulation of such single-use plastic products in environmental matrices. It is estimated that plastics constitute a substantial portion of global medical waste. For instance, daily medical waste generation in Asia reaches approximately 16,659.48 tons, while in the United States, annual medical waste amounts to about 5.9 million tons, of which plastic waste represents 1.7 million tons, accounting for approximately 28.8% of the total [20]. Once released into the environment, medical plastic debris can undergo further degradation through weathering processes—distinct from the natural degradation pathways of environmental MPs (e.g., oceanic or soil weathering)—leading to increased MMPs flux [21]. Furthermore, these MMPs can adsorb pathogenic microorganisms on their surfaces, forming a “plastisphere” effect [22], which significantly amplifies their biohazard potential.

3.2. Origin, Formation, and Classification of MMPs

Plastics play a pivotal role in modern medical systems, particularly in the domains of sterile packaging and precision surgical instruments, where their importance is irreplaceable [23]. Based on their origin and formation mechanisms, MMPs can be categorized into primary and secondary MMPs (Table 1).

Primary MMPs are synthetic polymer particles that are deliberately engineered and manufactured for specific medical applications, offering distinct advantages in the field of targeted drug delivery [24]. For instance, employing polymer microspheres or nanoparticles as carriers enables the precise delivery of active pharmaceutical ingredients to be targeted tissues or organs, facilitating site-specific drug release [25]. Moreover, by modulating drug release kinetics, such MMPs allow for sustained and controlled drug release, which not only contributes to mitigating the risks associated with drug overdose due to fluctuations in blood concentration but also enhances clinical efficacy and promotes patient recovery [26].

Secondary MMPs originate primarily from the fragmentation of plastic products in medical environments under the combined effects of physical abrasion, chemical degradation, and biological processes, exhibiting highly heterogeneous morphological characteristics such as fibrous and irregular fragments [27]. In dental surgical settings, oral care products and restorative materials continuously release MMPs particles due to prolonged exposure to multiple mechanisms, including biomechanical friction, enzymatic hydrolysis by salivary esterases, and fluctuations in oral temperature and pH [28]. Furthermore, during drug infusion procedures, certain solution components can induce the generation of reactive oxygen species (ROS), thereby accelerating the aging of PP materials and carbon chain scission. This mechanism not only leads to the release of MMPs from medical devices during use but also results in the detection of consistent PP particles in hospital wastewater, establishing a complete pollution pathway from “device aging” to “human exposure” and further to “environmental migration”. Additionally, operational conditions such as autoclaving and long-term storage aging can further promote the physical degradation and micro fragmentation of surgical instrument housings and plastic packaging, thereby generating secondary MMPs [29].

Table 1. Origins and formation pathways of primary and secondary MMPs.

Feature	Source	Formation	Morphology	Scenarios	Ref
Primary MMPs	Designed for medical use	Controlled industrial synthesis	Uniform regular	Targeted drug carriers	[24,25]
Secondary MMPs	In-use medical plastic degradation	Physicochemical degradation	Heterogeneous irregular	Aging release from dental materials/infusion sets	[27,28,29]

Table 1. Origins and formation pathways of primary and secondary MMPs.

Feature	Source	Formation	Morphology	Scenarios	Ref
Primary MMPs	Designed for medical use	Controlled industrial synthesis	Uniform regular	Targeted drug carriers	[24,25]
Secondary MMPs	In-use medical plastic degradation	Physicochemical degradation	Heterogeneous irregular	Aging release from dental materials/infusion sets	[27,28,29]

4. Human Exposure Routes to MMPs

Studies have revealed that MPs are now widely detected in various human biological samples [30]. Specifically, MPs particles have been identified in a range of tissues and bodily fluids, including the placenta [31,32], breast milk [33], feces [34,35], blood [36,37], thrombi [38,39], sputum [40], respiratory secretions [41], lung tissue [42] and cirrhotic liver tissue [43]. While existing evidence confirms the presence of MPs in the human body, their definitive entry pathways remain unclear and warrant further investigation. This section will elaborate on the exposure routes of MMPs from both direct and indirect perspectives.

4.1. Direct Exposure Route

The direct exposure route refers to scenarios where MMPs are introduced directly and immediately into a patient’s body during medical interventions. This occurs primarily through two principal pathways: invasive medical procedures and intravenous infusion systems. The following sections will detail their release mechanisms and quantify the associated risks.

4.1.1. Invasive Medical Procedure

Surgical procedures represent a core clinical intervention. However, they also create potential pathways for the introduction of MMPs particles into human tissues and the systemic circulation [44]. As illustrated in Figure 3A, Liu et al. conducted a clinical study on 23 patients with coronary artery disease undergoing PCI. They reported that interventional devices (guidewires, catheters, balloons, and stents) release MMPs through friction and collision during the procedure and these MMPs are introduced directly into the patient’s bloodstream, resulting in a marked increase in MMPs from 4.96 ± 3.40 to 93.57 ± 35.95 particles per 10 mL of blood postoperatively [12]. In cardiac surgery, similar evidence also exists. A study conducted by Professor Yang’s research team demonstrated that nine types of MMPs (with a maximum diameter of 469 µm) were detected in the pericardium and myocardial tissue of 15 patients who underwent cardiac surgery. The types and size distribution of MMPs in postoperative blood showed significant alterations compared to preoperative levels, and the poly (methyl methacrylate) (PMMA) detected in tissues such as the left atrial appendage could not be attributed to surgical contamination, directly proving the introduction of MMPs during the procedure [45]. Furthermore, Field et al. conducted a pioneering quantitative study on atmospheric MPs pollution within the unique indoor setting of a hospital operating theater. Over a one-week sampling period with 12 h intervals, the research systematically evaluated the concentration, polymer types, and particle-size distribution of microplastics in a cardiothoracic operating room and its adjoining anaesthetic room. Study findings indicate that MPs levels were significantly higher than those measured in domestic indoor environments and were directly correlated with surgical activity, as MPs were largely undetectable during non-working hours. The detected MPs were predominantly within inhalable size ranges, and polymer analysis identified PET and PP as the most abundant types, implicating common sources such as instrument blister packs and disposable surgical gowns/drapes [46]. This evidence substantiates that the surgical setting constitutes a notable point source for direct respiratory inhalation exposure to MPs for both patients and staff. Meanwhile, evidence indicates that these MPs can migrate across vascular endothelial gaps into peripheral tissues, potentially inducing localized inflammatory responses [47].

4.1.2. Intravenous Infusion System

Infusion procedures represent a critical pathway for the direct introduction of MMPs into the bloodstream [48]. As illustrated in Figure 3B, a recent study by Zheng et al. systematically quantified the release of micro- and nanoplastics from disposable PVC infusion sets under simulated clinical conditions using fluorescence-based methods. The study demonstrated that such sets not only carry intrinsic PVC particles but also release them during infusion, with the quantity and size distribution of released particles influenced by infusion duration, temperature, and fluid composition. Significantly higher levels are observed with alkaline solutions (e.g., 5% sodium bicarbonate) compared to isotonic saline (0.9% sodium chloride) over the same infusion duration. Notably, the MMPs release flux demonstrated dynamic characteristics, exhibiting an exponential accumulation trend with prolonged infusion time and elevated ambient temperature. This time–temperature synergistic effect establishes infusion as a significant source of intravenous MMPs exposure [49]. Subsequent investigation by Mou et al. demonstrated that the concentration of MMPs in the initial 12 mL flush of intravenous infusion was significantly higher than in the subsequent fluid, indicating a pronounced initial pulse release of MMPs during the early phase of infusion. Furthermore, the study revealed a distinct time-dependent increase in MMPs release, with the total mass of MMPs released from the infusion tubing rising progressively as the infusion duration extended from 1 to 4 h, from 0.3 ± 0.1 µg to 0.8 ± 0.3 µg. These findings confirm that infusion duration and temperature are critical factors governing MMPs release, clarifying the spatiotemporal distribution characteristics and associated exposure risks of MMPs during intravenous therapy [50].

4.2. Other Exposure Routes

In addition to direct pathway into the circulatory system, MMPs may access the human organism via a range of additional routes (Figure 3C). Long-term storage of oral medications in plastic containers made of materials such as PVC and PP may lead to the release of MMPs due to material aging and adsorption of drug components by the packaging, resulting in the simultaneous ingestion of MMPs by patients during medication administration [51]. Additionally, the heating process involved in preparing traditional Chinese medicine may cause its plastic packaging to release MMPs, thereby creating an exposure route that enters the human body through oral intake [8]. For topical pharmaceuticals and medical supplies, nanoplastic particles smaller than 200 nm can penetrate the stratum corneum barrier through skin folds, lipid pathways, and hair follicles, thereby permeating into the body [52,53]. Beyond that, respiratory assistive devices manufactured from plastic polymers tend to release micro- and nanoscale plastic particles under conditions of heating or exposure to water vapor, which can then be inhaled into the human body during breathing [54]. Notably, MPs have also been detected in the air of hospital and surgical environments, indicating that humans can be directly exposed to airborne MPs via inhalation [46,55].

For the general population, MMPs contribute relatively little to total MPs exposure compared to environmental pathways. The indirect MMPs exposure routes discussed herein are specific to medical-related scenarios (e.g., medical packaging, topical products) rather than general environmental intake. Although medical pathways such as intravenous infusion and surgery can lead to significant individual exposure in specific scenarios, such exposure is limited to individuals undergoing treatment and is intermittent. Therefore, at the public health level, while continuing to focus on environmental MPs control, it is critical to strengthen MMPs risk management in the medical field to ensure patient safety.

5. Multisystem Toxic Effects of MMPs

In medical contexts, MPs predominantly originate from plastic-based devices, packaging materials, and drug delivery systems, entering the human body through routine use, material degradation, or direct administration [56,57,58]. Their adverse impacts on cells and tissues are mediated through a combination of physical interactions and chemical mechanisms [53]. This section draws on existing evidence from in vitro and animal models to elucidate the key pathways through which MMPs may exert toxic effects on the cardiovascular, respiratory, digestive, and reproductive systems, thereby providing a theoretical basis for a comprehensive risk assessment (Table 2).

5.1. Cardiovascular Toxicity

During medical interventions such as dialysis and infusion, exposed MMPs can directly enter the systemic circulation, where they achieve relatively elevated local concentrations and circumvent the body’s natural barrier defenses [59,60]. As shown in Figure 4A, extracorporeal circulation circuits can release particles due to pump shear forces and sterilization-induced degradation, causing the patient’s postoperative blood MMPs concentration to rise from 3.54 µg/g to 7.62 µg/g [61]. MMPs released from infusion systems (e.g., PP infusion bags) can accumulate in cardiovascular tissues, with release quantities influenced by clinical usage frequency and duration. Currently, multiple lines of evidence have confirmed that the accumulation of MMPs in myocardial tissue and vascular plaques correlates with the severity of cardiovascular diseases, and the toxicological mechanisms are closely associated with the characteristics of medical exposure [62,63].

MMPs induce cardiovascular toxicity primarily through three mechanisms: myocardial injury, vascular inflammation, and thrombosis. However, most evidence is derived from animal models or in vitro studies, and the dose–response relationship in clinical populations remains unclear. Mechanistically, in vitro studies using cardiomyocyte models have shown that 50 nm polystyrene nanoplastics (PS-NPs) significantly upregulate homeodomain interacting protein kinase 2 (HIPK2), subsequently activating the P53 signaling pathway. In these experimental systems, this process increased cardiomyocyte apoptosis by 35–40% and activated the TGF-β1/Smad3 signaling pathway, inducing myocardial fibrosis—suggesting a potential mechanism for cardiomyocyte homeostasis disruption, though direct clinical evidence in humans remains unestablished [64] (Figure 4B). Secondly, elevated local concentrations of MPs strongly induce vascular inflammation and oxidative stress. In patients with acute coronary syndrome, circulating MPs levels correlate positively with coronary lesion complexity [65]. MPs concentration within femoral artery plaques can be tens to hundreds of times higher than in healthy arteries [66]. Marfella et al. provided the first evidence of MPs accumulation within human carotid artery atherosclerotic plaques (detection rate 58.4%). These MPs promote local oxidative stress and inflammatory responses, leading to a 4.53-fold increased risk of major adverse cardiovascular events [67]. Thirdly, once in the bloodstream, MMPs can immediately interfere with the coagulation system. Sheng et al. discovered that following entry into the systemic circulation, PS-NPs interact with plasma proteins. Specifically, their ready adsorption by coagulation factor XII and plasminogen activator inhibitor-1 significantly enhances the probability of thrombus formation [68] (Figure 4C). Clinical data also confirm that the incidence rate of thrombosis in long-term dialysis patients is 2–3 times that of the non-dialysis population [69], highlighting the unique cardiovascular risks associated with MMPs. However, current clinical evidence is predominantly based on correlational studies, lacking validation from prospective cohorts. Moreover, future research should prioritize elucidating the differential toxicity among various polymer types (e.g., PET, PP, PVC), their synergistic effects with pharmaceuticals, and the cardiovascular risks associated with chronic low-dose exposure.

5.2. Respiratory Toxicity

In clinical settings, MMPs constitute a significant source of human respiratory exposure to MPs, with exposure pathways characterized by both ubiquity and clinical specificity (Figure 5A). Firstly, airborne MPs in hospital wards can be directly inhaled through spontaneous breathing, serving as a baseline for long-term exposure in inpatients [55]. Secondly, respiratory therapy equipment such as ventilator circuits and humidifiers may release MMPs due to material wear or degradation during use and disinfection [54]. Furthermore, the manner of using protective gear influences exposure levels; for instance, repeated donning/doffing or storage in pockets can significantly increase MMPs’ release from masks, with related handling potentially doubling the dislodging of melt-blown fibers [70].

Existing evidence indicates that MMPs can lead to pulmonary function impairment and fibrosis by disrupting pulmonary surfactants and inducing cellular senescence and inflammation. Shi et al. observed that once deposited in alveolar regions, MPs preferentially adsorb phospholipid components of lung surfactants. This adsorption, in turn, induces oxidative stress by promoting hydroxyl radical (•OH) generation in simulated lung fluid, thereby compromising alveolar stability. While this effect is validated in vitro, the complexity of the physiological environment in vivo may attenuate its magnitude [71] (Figure 5B). Luo et al. demonstrated that MPs exposure upregulates the expression of circular RNA kif26b (circ_kif26b). The upregulated circ_kif26b functions by sequestering microRNA-346-3p (miR-346-3p), which alleviates the post-transcriptional repression of the cell cycle inhibitor p21. Consequently, the expression levels of senescence-associated proteins, including p21, p16, and p27, are elevated. These molecular alterations collectively induce cell cycle arrest and amplify the senescence-associated secretory phenotype (SASP), marked by increased secretion of inflammatory factors such as Interleukin-6 and Interleukin-8 (IL-6, IL-8). This enhanced inflammatory response ultimately contributes to the progression of pulmonary fibrosis [72] (Figure 5C). Moreover, in patients with prolonged respiratory support, MMPs can induce airway damage, leading to impaired ventilatory function and airway remodeling [73]. They disrupt bronchial tight junctions, compromising epithelial integrity and increasing infection risk [74]. Additionally, MPs can adsorb typical pollutants present on PM_2.5, forming composite particles [75], significantly exacerbating oxidative stress and inflammatory responses. Although existing studies have demonstrated the adverse effects of MMPs on the respiratory system, research to date has primarily focused on PS particles, lacking systematic comparisons of toxicity across different polymers and shapes. Additionally, quantitative data on MMP release from medical devices remain insufficient, hindering the establishment of a clinical dose–response relationship between exposure and lung injury.

5.3. Digestive Toxicity

Medical practice represents a notable route of human exposure to MMPs, with associated risks to digestive health requiring considerable concern. As shown in Figure 6A, long-term use of enteral nutrition support tubes, particularly PVC varieties, leads to the continuous release of MMPs and plasticizers, influenced by body temperature and nutritional solution composition [76]. Similarly, storage of oral medications in plastic containers over extended periods—ranging from months to years—can promote the release and accumulation of MMPs and related additives within pharmaceutical formulations [51]. Additionally, certain drugs may lose active ingredients due to adsorption by plastic containers during storage, as observed with diazepam and nitroglycerin in PVC materials [77].

Following their introduction into the digestive system through the noted routes, MMPs can drive hepatic and intestinal injury via distinct pathogenic mechanisms. Studies suggest that its mechanisms involve lipid metabolism dysregulation, intestinal barrier disruption, and microbiota dysbiosis. Fan et al. demonstrated that PS-NPs disrupt lysosomal function and dysregulate the AMPK/ULK1 pathway, leading to impaired lipophagy and subsequent lipid accumulation in hepatocytes [78] (Figure 6B). While this mechanism has been confirmed in animal models, it remains unclear whether human hepatocytes exhibit a similar sensitivity to MMPs. Furthermore, MPs pose direct and complex threats to the intestine itself, acting as vectors for pollutants (e.g., by adsorbing heavy metals) and facilitating their co-entry into intestinal epithelial cells (IECs). As investigated by Shaoyong et al., heavy metal-adsorbed aged MPs can activate the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) [79] inflammasome within IECs, triggering inflammatory cascades involving cysteine-dependent aspartate-specific protease 1 (Caspase-1)-mediated pyroptosis and increased interleukin-1β (IL-1β) secretion. These processes downregulate the expression of the tight junction protein occludin, markedly compromising intestinal barrier integrity [80] (Figure 6C). It is noteworthy that the combined toxicity of aged MPs and heavy metals may substantially exceed that of MPs alone. Additional studies indicate that MPs can induce the mechanism known as danger-associated molecular patterns through Toll-like receptors, thereby triggering an inflammatory cascade in mammalian cells [81]. Furthermore, MPs and their leached chemical additives disrupt intestinal microbiota balance [82] and form a vicious cycle with gut inflammation. Simultaneously, high concentrations of MPs themselves can lead to decreased cellular viability in intestinal cells [83]. Collectively, these mechanisms demonstrate that MMPs exposure constitutes a systemic health risk factor, with effects extending from local intestinal barrier impairment and dysbiosis to hepatic metabolic disturbances. However, most studies on digestive toxicity have employed single polymers or high-concentration exposures, failing to reflect the realistic clinical scenario of mixed polymers with low-dose, long-term exposure. Furthermore, the role of the gut–liver axis in MMPs’ toxicity remains to be elucidated.

5.4. Reproductive and Endocrine Toxicity

MMPs can enter the human circulatory system directly through pathways such as intravenous infusion, invasive procedures, or degradation of medical devices [13,45,46,49,50]. They subsequently disseminate via the bloodstream and accumulate in various organs and cells, including male and female gonads, posing direct risks to the reproductive system (Figure 7A). Studies have detected diverse MPs polymers in ovarian follicular fluid and endometrial tissues [84,85], with their presence associated with ovarian endocrine dysfunction and linked to gynecological surgeries and related medical devices as significant contamination sources. These particles have also been widely identified in testicular tissues and semen [86], where they contribute to male infertility by disrupting spermatogenesis, impairing sperm quality, and disturbing hormonal homeostasis.

The reproductive toxicity of MPs involves complex, multi-pathway mechanisms. In the female reproductive system, MPs directly disrupt ovarian endocrine function, including altering follicle-stimulating hormone levels [87], and act synergistically with contaminants like phthalates to increase follicular atresia and polycystic ovary syndrome risk [88]. At the molecular level, MPs promote cancer cell proliferation by interfering with estrogen signaling [89]. Specifically, PS-NPs could upregulate the expression of thrombomodulin (THBD) and inhibit the assembly of the nuclear factor kappa B (NF-κB) complex. This process activated the NF-κB signaling pathway, thereby promoting macrophages to enhance the secretion of tumor necrosis factor (TNF) and IL-6. This process triggered early reprogramming of the tumor microenvironment (TME), ultimately facilitating abnormal tumor proliferation and development [90] (Figure 7B). In the male reproductive system, MPs induce toxicity through endocrine disruption, including reduced testosterone bioavailability, which compromises the spermatogenic microenvironment [91]. MPs also trigger oxidative stress, activate PPARγ signaling, and impair lipophagy, leading to lipid dysregulation and testicular injury [92]. Furthermore, MPs exhibit transgenerational toxicity by crossing the placental barrier and accumulating in offspring testes [93]. This exposure induces overexpression of the key transcription factor PR domain-containing 14 (Prdm14) in undifferentiated spermatogonia (Undiff-SPG). Prdm14 overexpression suppresses the expression of key genes (Ccdc33, Tcirg1) and spermatogenesis-related proteins (Osbp2, Zcwpw1, Dhps), which is concomitant with reduced sperm concentration, decreased motility, and an increased abnormality rate, ultimately resulting in impaired spermatogenesis in the offspring [94] (Figure 7C). Although animal studies provide evidence of the harmful effects of microplastics on the reproductive system, it is important to note that the discussed reproductive toxicity research relies heavily on animal models, while human epidemiological data remain scarce. Future research should prioritize exploring the combined toxicity of MMPs with common endocrine disruptors, sex-specific sensitivity, and impacts on assisted reproductive technology outcomes.

Table 2. Summary of MMPs’ multisystem toxic effects.

Affected Systems	Exposure Routes	Core Toxic Effects	Molecular Mechanisms	Research Evidence Types	Overall Trends	Ref
Cardiovascular	Dialysis, invasive, IV	Injury, Inflammation, Thrombosis	Oxidative stress, P53	In vitro, Animal, Clinical	Disease of severity link	[64,67,68]
Respiratory	Ward air, Ventilators, Mask	Fibrosis, Barrier damage	•OH generation, SASP	In vitro, Animal, BALF	Inhalation widespread	[71,72]
Digestive	Feeding tubes, Drug packs	Lipid accumulation, Barrier disruption	AMPK/ULK1, NLRP3	In vitro, Animal, Limited	Chronic low-dose risk	[78,80]
Reproductive	IV, Invasive, Placental	Dysfunction, Impaired sperm	Estrogen interference, Prdm14	Animal, Limited clinical	Synergistic toxicity	[90,94]

Table 2. Summary of MMPs’ multisystem toxic effects.

Affected Systems	Exposure Routes	Core Toxic Effects	Molecular Mechanisms	Research Evidence Types	Overall Trends	Ref
Cardiovascular	Dialysis, invasive, IV	Injury, Inflammation, Thrombosis	Oxidative stress, P53	In vitro, Animal, Clinical	Disease of severity link	[64,67,68]
Respiratory	Ward air, Ventilators, Mask	Fibrosis, Barrier damage	•OH generation, SASP	In vitro, Animal, BALF	Inhalation widespread	[71,72]
Digestive	Feeding tubes, Drug packs	Lipid accumulation, Barrier disruption	AMPK/ULK1, NLRP3	In vitro, Animal, Limited	Chronic low-dose risk	[78,80]
Reproductive	IV, Invasive, Placental	Dysfunction, Impaired sperm	Estrogen interference, Prdm14	Animal, Limited clinical	Synergistic toxicity	[90,94]

5.5. Limitations and Uncertainties in MMPs Health Risk Assessment

While existing in vitro and animal studies have underpinned the understanding of MPs-induced toxicity in the cardiovascular, respiratory, digestive, and reproductive systems mediated by pathways such as oxidative stress, inflammation, and autophagy dysfunction [64,71,78,94], the translational relevance of these findings to humans is constrained. In vitro models often use unrealistic high concentrations and isolated cells that diverge from clinical exposure scenarios [49,67], animal models suffer from species-specific metabolic disparities and fail to replicate clinical exposure routes or vulnerable patient populations [61], extrapolation to humans faces uncertainties in dose–response scaling and individual variability, and inconsistent detection methods and experimental protocols hinder data comparability [95,96]. These constraints highlight the need to acknowledge methodological gaps, avoiding overinterpretation of current evidence to support credible MMPs health risk assessment.

6. Advances in Analytical Techniques for MMPs

In the field of medical and clinical research, the detection of MMPs faces a series of unique challenges, notably the lack of standardized sampling and analytical methods [97], as well as high false-positive risks from contamination during sample collection, pretreatment, and instrument analysis [17,97]. Many studies have confirmed that plastic lab consumables such as disposable gloves and plastic centrifuge tubes can release microfibers or particles, which may be misidentified as MMPs in biological samples [17,98]. Therefore, contamination control has become a critical prerequisite for ensuring the reliability of MMPs detection results. Currently, the primary techniques for MMPs detection in biological matrices such as blood, tissue, and other body fluids are centered around three categories: microscopic imaging techniques, spectroscopic analytical techniques, and chromatography–mass spectrometry hyphenated techniques (Figure 8). As systematically compared in Table 3, these methods exhibit distinct characteristics in terms of limit of detection (LOD), qualitative/quantitative capabilities, information dimensions, and applicable scenarios. Microscopic imaging provides direct particle morphology and size data but offers limited submicron resolution and insufficient chemical specificity, requiring strict sample stage cleaning and non-plastic sample carriers to avoid contamination [99]. Spectroscopy enables simultaneous morphological and chemical polymer identification, yet its resolution is constrained by optical diffraction and is sensitive to sample physical state, with blank scanning of non-sample areas necessary to exclude instrument background contamination [100]. Chromatography–mass spectrometry delivers exceptional chemical specificity and sensitivity for trace analysis, but its complex pretreatment and prolonged analysis time hinder high-throughput applications, and frequent replacement of inlet liners and solvent flushing of chromatographic columns are required to prevent cross-contamination [101].

Notably, unlike environmental MPs detection that focuses on bulk matrix analysis, MMPs detection has driven targeted technical innovations to address the specificity of biological samples (e.g., high water content, complex organic matrices, and ultra-trace particle levels). Therefore, technique selection should weigh the specific detection objectives of physical characterization or chemical analysis or employ complementary approaches.

6.1. Scanning Electron Microscope Coupled to Energy Dispersive X-Ray Spectroscopy

Given the capability of scanning electron microscopy (SEM) in characterizing the three-dimensional morphology of MPs, it is commonly coupled with an energy dispersive spectrometer to form the SEM-EDS technique, thereby enabling discrimination between carbon-dominated MPs and inorganic particles while providing elemental composition information [102]. To minimize contamination interference in medical sample analysis, the sample stage should be covered with aluminum foil and wiped with anhydrous ethanol before each test, and glass or metal sample holders should be used instead of plastic ones.

In medical detection scenarios, this method has been successfully applied to the analysis of MPs in various biological samples. Baeza-Martínez et al. conducted a systematic analysis of bronchoalveolar lavage fluid (BALF) samples and found that MPs pollutants predominantly existed in the form of microfibers, accounting for 97.06% of the total, with an average concentration of 9.18 ± 2.45 items/100 mL BALF [103]. In a separate study, Li et al. utilized SEM-EDS to analyze intravenous infusion products, revealing that the identified MPs particles were predominantly irregular or near-spherical in morphology, with size ranges from 10 nm to 3.6 µm. Quantitative analysis revealed that MPs concentrations during intravenous therapy can reach (5.82 ± 0.86) × 10⁴ items/L, thereby demonstrating a substantial particulate contamination risk in clinical infusion solutions [98]. Building upon conventional SEM-EDS technology, an innovative variable-pressure SEM with dual EDS detectors (VP-SEM-dEDS) enables direct imaging and chemical mapping of hydrated biological tissues under low-vacuum conditions. Applied to ten human placenta samples, this technique identified exogenous carbon-rich microparticles ranging from 2.1 to 18.5 µm on villous surfaces. Through elemental mapping, these microplastics were distinguished from the surrounding tissue by their characteristic high-density carbon signatures, establishing a reliable and artifact-minimized method for detecting plastic contamination in clinical specimens at micrometer resolution [104].

However, SEM-EDS faces technical limitations in detection of MPs, including suboptimal resolution for submicron particles and limited specificity in identifying organic polymers, making it difficult to accurately discriminate between hydrocarbon polymer homologs such as PE and PP [97]. Additionally, the electron gun and detector need to be cleaned in a timely manner after detection to avoid cross-contamination between samples. Consequently, it is often necessary to integrate molecular vibrational spectroscopy techniques such as Fourier transform infrared (FTIR) spectroscopy and Raman spectroscopy. These methods enhance the reliability of polymer type identification by providing molecular-level information, including C-H/O-H stretching vibrations and characteristic peaks in the fingerprint region [105].

6.2. Micro-Fourier Transform Infrared Spectroscopy

FTIR spectroscopy has become a critical analytical technique in environmental science due to its efficient detection capability for MPs within complex environmental matrices [106]. As a spatially resolved extension of FTIR technology, µFTIR enables nondestructive analysis of target polymers while simultaneously acquiring both characteristic chemical fingerprint spectra and micromorphological features, thereby significantly enhancing the sensitivity and specificity of MPs detection [107]. For medical sample analysis, CaF₂ or KBr materials should be selected for the sample cell, and nitrogen purging should be performed for 10 min before detection to remove residual particles. Metal fixtures should be used instead of plastic sample holders to avoid contamination from plastic components.

The µFTIR technique has been successfully applied to detect MPs in medical samples such as human tissues and blood. The team led by Jenner was the first to successfully detect and quantify MPs in human lung tissue using µFTIR spectroscopy, which has a size detection limit of ≥3 µm. Their analysis revealed an average MPs abundance of 1.42 ± 1.50 MP/g of lung tissue, with PP (23%) and PET (18%) identified as the predominant polymer types [95]. In another study, Leonard’s team detected 24 types of polymers in 90% of human blood samples using µFTIR. Using a limit of quantification (LOQ) approach, five polymer types were quantified above the threshold, with a mean concentration of 2466 ± 4174 MP/L. The analyzed plastic concentrations in the blood samples ranged from 1.84 to 4.65 µg/mL. The particle dimensions varied widely, with lengths ranging from 7 to 3000 µm and widths from 5 to 800 µm [108].

Despite its unique advantages such as non-destructive analysis and the simultaneous acquisition of chemical fingerprints and morphological information, µFTIR technology is constrained by the optical diffraction limit in spatial resolution and imposes stringent requirements on sample thickness, homogeneity, and water content. To address water interference in biological samples, label-free optical photothermal infrared (O-PTIR) spectroscopy has been developed for medical use. Leveraging 500 nm spatial resolution (instrument maximum) and targeting key bands (e.g., 1740 cm⁻¹ for lipids, 1656 cm⁻¹ for proteins), it enables in situ analysis of fresh hydrated tissues without dehydration, bridging the gap between dry- and wet-sample infrared detection [109]. This optimization is exclusive to clinical detection and fills the gap between environmental dry-sample µFTIR and wet biological sample analysis. However, the detection results are easily affected by the water content of biological samples, and proper sample dehydration treatment is required while avoiding the use of plastic dehydration containers [100]. To overcome these limitations, it is often necessary to employ Raman spectroscopy as a complementary analytical technique.

6.3. Raman Spectroscopy

The capability of Raman spectroscopy for high-precision analysis of MPs is attributed to its submicron spatial resolution and minimal interference from water molecules [110]. This makes the technique particularly effective for the identification of particles with diameters down to 1 µm [111]. Before laser focusing, it is necessary to scan the blank area of the glass slide without samples to exclude background contamination from the instrument itself. Glass slides should be used instead of plastic ones to avoid particle release from plastic materials affecting detection results.

Raman spectroscopy provided direct spectroscopic evidence for the presence of MPs in human thrombi. In the study by Wu et al., Raman spectroscopy, which enables detection of particles with a size limit of ≥1 µm, was employed to systematically analyze 26 human thrombus samples. A total of 87 exogenous microparticles were identified, ranging in size from 2.1 to 26.0 µm. Among these, one particle was identified as low-density polyethylene (LDPE), accounting for approximately 1.15% (1/87) of the total detected particles [112]. Similarly, Massardo et al. detected MPs in human urine and renal tissue through Raman spectroscopy. Analysis of 10 kidney samples and 10 urine samples led to the identification of 26 MPs particles, with sizes ranging from 3 to 13 µm in urine samples and 1 to 29 µm in kidney samples. The most frequently identified polymer types were PE and polystyrene (PS) [113].

Despite the excellent performance of Raman spectroscopy in MPs detection, the technique is susceptible to fluorescence interference, which limits its identification capability for dark/strongly fluorescent polymers [114]. In addition, biological tissues may have spontaneous fluorescence, requiring the selection of 638 nm laser wavelength and blank tissue controls to reduce false-positive signals. A medical Raman breakthrough is the combination of surface-enhanced Raman scattering (SERS) with citrate-reduced silver nanoparticles (cit-Ag NPs), achieving two key advances. First, it attains single-molecule sensitivity for ultra-trace targets, overcoming conventional Raman’s limitation for nanoscale analytes; second, it enables specific recognition of biomolecule-bound targets in tissues, a gap rarely addressed in environmental studies [115]. Furthermore, for the comprehensive analysis of MPs, especially in complex environmental matrices, coupling Raman or SERS with chromatographic–mass spectrometric techniques is often necessary to enhance polymer identification, quantification, and additive profiling.

6.4. Pyrolysis–Gas Chromatography–Mass Spectrometry

When detecting MPs in complex matrices, chromatography–mass spectrometry techniques demonstrate significant advantages [116]. For pyrolysis–gas chromatography–mass spectrometry (Py-GC-MS) analysis of medical samples, glassware should be used throughout the sample pretreatment process to avoid particle dissolution from plastic consumables. The inlet liner needs to be replaced after every 50 samples to prevent residual polymer cross-contamination.

In medical research, Py-GC-MS has been applied to detect MPs in human tissues and body fluids. Liu et al. conducted a quantitative analysis of MPs in three types of human arterial tissues using Py-GC-MS, a method capable of detecting MPs down to 0.02 µg. MPs were identified in all 17 arterial specimens, with an average concentration of 118.66 ± 53.87 µg/g tissue. Four polymer types were detected, dominated by PET (73.70%), followed by PA-66 (15.54%), PVC (9.69%), and PE (1.07%) [96]. Tian et al. analyzed MPs in human amniotic fluid using Raman spectroscopy and Py-GC-MS, detecting MPs in 81.25% of 48 samples. The identified MPs particles exhibited an average size of 3.05 ± 1.05 µm, with a size distribution ranging from 0.94 to 5.73 µm. Systematic quantitative analysis further revealed that polytetrafluoroethylene (PTFE), PS, and acrylonitrile-butadiene-styrene (ABS) were the predominant polymer types, with detection rates of 31.25%, 20.83%, and 14.58%, respectively [117].

Table 3. Mainstream detection methods of MPs.

Type	LOD *	Qualitative/ Quantitative	Information Dimension	Application Scenarios	Ref
SED-EDS	≤10 nm	Qualitative/Semi-quantitative	Elemental Morphological	Surface characterization	[98,103]
µFTIR	≥3 µm	Qualitative	Chemical composition	Tissue analysis	[95,108]
Raman spectroscopy	≥1 µm	Qualitative	Chemical Morphological	Particle profiling	[112,113]
Py-GC-MS	0.02 µg	Qualitative/Quantitative	Polymer mass	Mass screening	[96,117]

* Values denote either minimum detectable particle size or mass.

Table 3. Mainstream detection methods of MPs.

Type	LOD *	Qualitative/ Quantitative	Information Dimension	Application Scenarios	Ref
SED-EDS	≤10 nm	Qualitative/Semi-quantitative	Elemental Morphological	Surface characterization	[98,103]
µFTIR	≥3 µm	Qualitative	Chemical composition	Tissue analysis	[95,108]
Raman spectroscopy	≥1 µm	Qualitative	Chemical Morphological	Particle profiling	[112,113]
Py-GC-MS	0.02 µg	Qualitative/Quantitative	Polymer mass	Mass screening	[96,117]

* Values denote either minimum detectable particle size or mass.

Although Py-GC-MS enables polymer identification of MPs through characteristic pyrolysis products, its application is constrained by complex sample preparation procedures and an analysis time typically exceeding 30 min per sample, which limits high-throughput analysis [101]. To address these limitations in clinical settings, a modified double-shot Py-GC-MS method has been developed. It detects four types of MPs (≥300 nm) in biological samples with RSD 6.50–20.68%, using P(E-¹³C₂) as internal standard, supporting combined health risk assessment rarely covered in environmental applications [118]. It should be noted, however, that the high-temperature pyrolysis process may cause the release of plastic components from the instrument’s internal pipeline, requiring regular maintenance and cleaning of the instrument.

The accurate detection of MPs in complex biological samples like tissues and blood poses significant challenges in the medical field. Single analytical methods are often insufficient for multiparameter identification. Therefore, researchers are increasingly turning to strategies that combine multiple techniques to improve detection reliability and obtain more comprehensive information. For instance, integrating microscopy with Raman spectroscopy enables simultaneous morphological observation and chemical composition analysis, significantly improving detection accuracy [119]. Coupling chromatographic–mass spectrometric techniques with FTIR allows for the determination of MPs polymer types while enabling mass-based quantification, thereby enhancing detection sensitivity [120]. Furthermore, the application of methods such as fluorescent staining [121] and receptor-based assays [122] effectively mitigates inaccuracies caused by the limitations and false-signal interference inherent in single-method approaches. These integrated approaches not only improve the accuracy and comprehensiveness of MPs detection but also provide a stronger technical foundation for assessing human exposure levels, distribution patterns, and potential health effects.

7. Challenges and Prospects

This review systematically elucidates the release mechanisms of MMPs during their production and application and details their multiple exposure pathways through which they enter the human body. These include direct routes (e.g., surgical intervention, intravenous infusion) and indirect routes (e.g., inhalation of airborne particles in clinical settings, ingestion via orally administered drugs stored in plastic containers, and dermal absorption from topical medical products). Furthermore, it elucidates the potential molecular pathways of multi-organ toxicity induced by MMPs, which are closely associated with their release characteristics in medical environments. Specifically, MMPs have been shown to trigger oxidative stress, inflammatory responses, apoptotic pathways, and dysregulated autophagy across cardiovascular, respiratory, digestive, and reproductive systems. These processes contribute to pathological outcomes such as myocardial injury, pulmonary fibrosis, hepatic steatosis, intestinal barrier dysfunction, and impaired spermatogenesis.

Notwithstanding this established conceptual framework linking MMPs to health risks, significant research and translational gaps persist, posing challenges for risk assessment and management. Firstly, standardized methods for detecting and quantifying MMPs in complex biological matrices (e.g., blood, tissue) and clinical environments are lacking. Inconsistencies in sampling protocols, particle size detection limits, and contamination control severely hinder data comparability and reliable exposure assessment. Secondly, the toxicological database remains insufficient, particularly regarding the chronic effects of low-dose, recurrent MMPs exposure—a scenario common in patients undergoing long-term or repeated medical treatments. The potential for synergistic toxicity with pharmaceuticals, leaching additives, or co-pollutants adsorbed onto MMPs also requires elucidation. Additionally, the development of safe and environmentally friendly alternative materials for medical plastics is progressing slowly, failing to meet the clinical demand for materials that combine biocompatibility with environmental sustainability. Finally, the absence of a unified global regulatory framework means that effective management and control of MMPs lack a solid legal basis.

To overcome these bottlenecks, future research must focus on the following key directions. Priority must be given to developing and validating standardized analytical methodologies suitable for clinical and environmental monitoring of MMPs. Robust longitudinal studies and advanced vitro models (e.g., patient-derived organoids) are needed to characterize the long-term health outcomes and underlying mechanisms of MMPs exposure. Moreover, it is essential to accelerate the development of biodegradable polymer materials and thoroughly investigate their feasibility in replacing traditional non-degradable plastics in various medical devices, thereby reducing the generation and release of MMPs at the source. Ultimately, translating scientific evidence into policy is crucial; integrating MMPs risk considerations into medical device safety evaluations and healthcare waste management protocols will be essential for protecting patient health and environmental sustainability.

In conclusion, while the link between medical plastic use and human exposure to MMPs is now evident, bridging the knowledge-to-action gap demands a concerted, interdisciplinary effort. By advancing detection science, deepening mechanistic toxicology, innovating in materials design, and strengthening regulatory oversight, the healthcare sector can mitigate the risks posed by MMPs and move toward a more sustainable and safer practice.