Pigment particle’s life-cycle

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1. Background

Pigment retention might appear straightforward, but the underlying processes are quite complex. To inform this article, insights were compiled from interviews with over 36 top-earning artists in their respective regions, with careers ranging from two to four years. A dermatologist, two chemists, and a cellular biology expert also reviewed and enhanced the content. It became evident that many professional artists have only a superficial understanding of pigment retention, finding much of the information presented here novel.

The interviews conducted for this article spanned from 2020 to 2024, with ongoing related research. Among the interviewed artists, 24 were based in the European Union, six in the UK, three in the US, and others in various Asian countries. Most specialize in the Powder Brows technique and often counsel clients on pigment retention matters.

2. From Bottle to the Lymphatic System

In this article, we trace the journey of pigment-colorant particles from the bottle to their ultimate destinations within the human body, distilling intricate biological interactions into five primary pathways a pigment particle might undertake upon entering the dermal layer.

Immediate Phagocytosis and Way to the Lymphatic System

This route involves the rapid uptake of pigment particles by phagocytic cells, which quickly transport them from the implantation site to the lymphatic system. It's a natural response of the body’s immune system to the trauma caused by the penetration of the dermis.

Undesirable Pathways: Migration, Reaching Hypodermis or Blood Vessels v In less desirable scenarios, particles penetrate too deeply beyond the reticular dermis. Depending on their properties, these particles may remain within the hypodermis's lipid-rich environment for an extended period. Similarly, direct transfer to blood vessels is uncommon and typically requires specific conditions.

Engulfment and Residence within Dermal Macrophages

Here, macrophages engulf pigment particles and serve as long-term pigment repositories within the dermal layer. This process potentially contributes to the colorant's longevity in the skin.

Agglomeration and Encapsulation by Fibroblasts

Pigment particles may cluster and become encapsulated by fibroblasts, forming a fibrotic shell that isolates the pigment within the dermal extracellular matrix (ECM). This encapsulation can impact the pigment's long-term stability and visibility in the skin.

Integration into the Extracellular Matrix (ECM)

Some pigment particles become trapped within the ECM, comprising various proteins and polysaccharides providing structural support to cells. This entrapment stabilizes the pigment particles, reducing their movement and affecting their fading rate.

In the detailed review, we'll explore each pathway to understand better the biological and chemical factors influencing post-implantation pigment particle behavior. We'll examine the impact of particle size, shape, and chemical composition on their fate and the body's immune responses that might degrade or retain these pigments in the skin.

Our comprehensive examination aims to elucidate the complex interaction between introduced pigments and the skin's biological systems. The goal is to present an informative narrative of the "life cycle" of pigment particles used in semi-permanent makeup, from insertion to potential fading or persistence.

3. Immediate Phagocytosis

Macrophage Involvement and Phagocytosis

During semi-permanent makeup procedures, the body's defense mechanisms activate when pigment is introduced into the skin. Initially, it mounts a generalized immune response, bringing cells like macrophages, histiocytes, and neutrophils to the insertion site. Macrophages are critical in phagocytosis, engulfing foreign particles up to 10 micrometers. Common pigment particles used in semi-permanent makeup, typically around 500 nm in diameter, fall well within the size range macrophages can handle. After ingestion, some macrophages may settle in the dermis, retaining pigment particles long-term.

Debunking Common Misconceptions

Particle versus Molecule. There's often confusion between 'molecule' and 'particle.' Pigment molecules differ from the larger particles they form. The particle size is relevant when considering the body's interaction with pigment, not the individual molecules.
Size and Phagocytosis. Contrary to some beliefs, larger particles (over 0.5 μm) are more efficiently phagocytized by macrophages. Particles smaller than 100-200 nm might evade phagocytosis, but other cellular uptake mechanisms might still come into play, contributing to pigment fading over time.
Immunogenic Response. The pigment's chemical properties and the physical disruption from the needle penetration initiate the immune response. This trauma activates the innate immune response, with neutrophils among the first responders, although they often struggle to clear the pigment.
Pigment in the Lymphatic System. Some pigment particles migrate to the lymphatic system, where they remain indefinitely. Lymph nodes lack mechanisms to break down or expel these pigments so that ink particles can be found in lymph nodes post-mortem.

4. Migration and Misplacement

Intravascular Entry

Accidentally introducing pigment particles into blood vessels is a rare but potential complication, especially in areas with "cold" skin tones where capillaries are more visible. The risk is higher during eyeliner procedures due to the vascular nature of the eyelids. Artists might mitigate this by gently massaging the area away from capillaries and using anesthetics to constrict blood vessels. In severe cases of vascular intrusion, stopping the procedure might be necessary.

Reaching the Hypodermis

Pigment particles can undesirably migrate into the hypodermis, causing a "blowout." Organic pigments, often rich in hydrocarbons, are particularly prone to this due to their lipophilic nature. They are drawn to the lipid-rich environment of the hypodermis, where they can persist if the artist penetrates beyond the reticular dermis.

Longevity of Particles in the Hypodermis

Organic pigment particles can remain in the hypodermis for extended periods. Their stability is due to lipophilic interactions between the pigment's organic components and the hypodermis's lipids. These particles blend with surrounding tissues, resisting metabolic or mobilization efforts by the body. Thus, pigments reaching the hypodermis can result in persistent, long-lasting discolorations. Limited regenerative activity in the hypodermis, characterized by slow cellular turnover, further contributes to the permanence of these pigments.

Consequently, practitioners aim to avoid misplacing pigment particles into the hypodermis. A clear understanding of pigments' structural and chemical nature can help artists prevent such complications and ensure pigments remain within the intended skin layers.

5. Residence in Dermal Macrophages

Engulfment and Residence within Dermal Macrophages

Macrophages are crucial in determining pigment retention, migration, or degradation, leading to various outcomes like transporting pigment particles to lymph nodes or retaining them in the skin.

Becoming Stationary

After ingesting pigment particles, some macrophages may become stationary and integrate into the dermis as long-term pigment repositories. However, it's an oversimplification to say these macrophages merely "die" and remain in the dermis with their engulfed contents. The reality of phagocytosis and subsequent macrophage behavior is complex and actively researched.

Chemical Reactions Inside Macrophages

There's no straightforward reaction formula for the degradation of iron oxide or carbon pigment particles. The degradation process involves various enzymes and reactive species and can be summarized as follows.

Inside the Phagolysosome. Once fused with a lysosome, pigment particles within a phagosome are exposed to a harsh, acidic environment filled with digestive enzymes and reactive oxygen species (ROS).
Digestion of Organic Pigments. These enzymes and ROS may sometimes break down organic pigments, varying widely based on the pigment's chemical structure.
Stability of Inorganic Pigments: Inorganic pigments like iron oxides are generally more stable and resist degradation within the phagolysosome. They might change oxidation states but remain largely intact.
Carbon Pigments: Carbon, being elemental, is inert under physiological conditions and resists chemical reactions.

Some macrophages undergo functional changes upon ingesting pigment particles, retaining the pigment in situ rather than transporting it to the lymphatic system.

Over time, a macrophage’s ability to retain pigment may diminish. As macrophages are continually replenished, there's a dynamic process of release and re-engulfment of pigment particles. If a macrophage releases a particle not immediately captured by a new macrophage, it may migrate to the lymphatic system.

Interactions Within Macrophages and Particle Fate

Enzymatic reactions inside macrophages can vary based on the particle's chemical composition, potentially altering their structure and color. The lifespan of a macrophage holding onto a pigment particle varies, influenced by the local tissue environment and the macrophage's activation state. As part of a renewable cell population, macrophages' involvement in pigment retention is transient and sustained.

The life cycle of a pigment particle within dermal macrophages involves phases of retention, possible degradation, and eventual release. This cyclical process is moderated by the body's continuous production of macrophages. Understanding this cellular process is vital for practitioners aiming to predict the longevity and fading of pigments in Powder Brows procedures.

6. Encapsulation by Fibroblasts

Specialized Immune Response

After the initial response, more specialized immune mechanisms involving T-lymphocytes and B-lymphocytes engage with foreign pigments. T-lymphocytes may target cells containing pigment, while B-lymphocytes produce antibodies. However, the role of B-lymphocytes in pigment response is less direct, as antibody-mediated pigment neutralization isn't a primary reaction in semi-permanent makeup.

Agglomeration and Particle Dynamics

Pigment particles may agglomerate within the skin. Individual skin properties like age, oiliness, collagen strength, and overall condition influence this complex process. Contrary to simplistic views that "small black particles are quickly removed," agglomeration depends on the particle's chemical nature. Smaller particles can form larger aggregates through chemical interactions and physical entanglements. These aggregates can stabilize within the skin's fibrous network when large enough, often through interactions with fibroblasts.

Stabilization and Encapsulation by Fibroblasts

Fibroblasts, responsible for producing the extracellular matrix and collagen, may encapsulate pigment aggregates. Upon pigment introduction, fibroblasts activate and may differentiate into myofibroblasts, which have enhanced contractile properties essential for tissue repair and encapsulation.

Myofibroblasts migrate towards pigment aggregates and encapsulate them with ECM components like collagen, elastin, and fibronectin, forming a fibrotic capsule around the clusters.

Functions and Remodeling of the Fibrotic Capsule

The fibrotic capsule isolates the pigment mechanically, reducing reactivity and shielding it from the immune system. However, this capsule isn't permanent and can remodel over time due to enzymatic activity and physical forces, potentially releasing pigment particles into the dermal environment.

Fibroblast-mediated encapsulation represents a critical yet dynamic endpoint for pigment retention in the skin. The journey of pigment particles through the immune system and stabilization in the dermal layer highlights the complex balance between the skin's biological environment and the physicochemical properties of pigments used in semi-permanent makeup. Understanding these interactions is crucial for artists aiming to predict and manage the outcomes of their procedures.

7. Retention in the Extracellular Matrix

The culmination of pigment encapsulation within the dermal layers involves integration into the extracellular matrix (ECM), a scaffold comprising proteins and polysaccharides that provide structural support and engage actively with skin cells. The ECM, rich in collagen, elastin, and glycosaminoglycans, plays crucial roles in cell signaling and tissue repair. Pigment particles introduced during semi-permanent makeup procedures interact with this matrix, potentially leading to their entrapment.

Considering retention, it's essential to account for the possible aggregation and agglomeration of pigment particles. The more conducive the chemical conditions are for bond formation between particles, the greater the likelihood of forming aggregates and clusters that can become entrapped in the dermis, such as in the ECM.

Mechanisms of Entrapment in the ECM

Physical Adsorption. The adherence of pigment particles to the ECM is influenced by their size, surface charge, and the charged domains of ECM proteins, anchoring the particles within the matrix.
Mechanical Interlocking. The ECM's fibrous network can ensnare pigment particles like a net capturing objects. This capture is more likely when ECM density is high, and particle geometry favors entrapment.
Biochemical Anchoring. ECM proteins can bind pigment particles through specialized interactions, enhancing stability and limiting migration.
Tissue Remodeling. The ECM may increase its synthesis around the introduced pigment, reinforcing the particle's anchorage within this newly formed matrix.

Implications of ECM Entrapment

Longevity and Stability. Entrapment within the ECM typically leads to prolonged retention and stability of pigment, reducing the risks of migration and degradation.
Immunological Shielding. While not as protective as fibroblast encapsulation, ECM entrapment offers some concealment from the immune system, contributing to pigment longevity.

Entrapment of pigment within the ECM is a key factor in the longevity of semi-permanent makeup. It demonstrates the dynamic interplay between the pigments and the skin's biological components, each influencing the other to maintain a delicate balance.

8. Additional Factors

What Else Influences Pigment Retention in the Skin

Pigment retention is an inherently transient process, although it can sometimes be prolonged. As a foreign material within the body, pigment is ultimately destined for the lymphatic system and subsequent removal, a process only halted by the finite lifespan of the human organism.

Pigmentation retention, particularly for semi-permanent makeup like Powder Brows, is complex and dynamic, influenced by various factors.
Biochemical Alterations. Medication, hormonal fluctuations, and radiation exposure can trigger changes in the skin's chemical environment.
Enzymatic Activity. The body's natural enzymatic processes constantly degrade foreign substances, including pigment agglomerates and particles.
Further Immune Response. The immune system continuously monitors and reacts to non-self entities, working to break down and clear pigments.
UV Radiation. Exposure to ultraviolet light catalyzes photochemical reactions, breaking down pigment particles. Resistance to UV light varies based on the pigment's inherent lightfastness, chemical composition, and particle size.
Environmental Factors. Elements like titanium dioxide (TiO2) in the skin can amplify the photodegradation of pigments due to their photocatalytic properties.
Cell Turnover. The skin's natural exfoliation process can lead to the loss of more superficially implanted pigments over time.
Oxidative Stress. Reactive oxygen species (ROS) generated in the skin can chemically alter pigments, leading to their breakdown.
Chemical Interactions. Interactions with other chemical compounds, whether produced within the body or applied externally (like skincare products), can modify pigments and facilitate their degradation.
Exocytosis. Macrophages and other phagocytic cells can ingest and, in some cases, expel pigment particles back into the interstitial fluid, where they can be removed by lymphatic drainage.

Exocytosis Explained

Exocytosis is a cellular process where cells eject materials they cannot process or need to eliminate. For macrophages dealing with pigment particles from tattoo ink or semi-permanent makeup, this process occurs when the macrophage engulfs the particle but cannot degrade it, then transports and expels it into the surrounding interstitial fluid. From there, the lymphatic system can carry the particle to the lymph nodes. While some particles are trapped in the lymph nodes, others may continue through the lymphatic system and either re-enter the bloodstream or be excreted.

Thus, the persistence of pigment within the skin depends on a delicate balance of external influences and internal physiological processes. Each factor contributes to the gradual fading of pigmentation, emphasizing the temporality of semi-permanent makeup applications.

9. Conclusions

When pigment particles enter the skin, they cause traumatization, initiating an innate immunogenic response. Subsequently, one of the five common scenarios typically occurs.

Immediate Phagocytosis and Migration to the Lymphatic System. Innate immune mechanisms are activated upon skin penetration. Pigment particles may be quickly engulfed by phagocytes, primarily macrophages, and transported to the lymphatic system for further processing or permanent residence.
Migration and Reaching the Hypodermis or Blood Vessels. Particles that evade initial phagocytic capture can inadvertently migrate to the hypodermis or, less commonly, into capillaries. Particles in the hypodermis may persist due to their chemical affinity for the lipid-rich environment or because they are beyond the typical reach of immune surveillance.
Engulfment and Residence within Dermal Macrophages. Some macrophages ingest pigment particles and become long-term repositories within the dermis. The lifespan of these macrophages and their pigment cargo can vary, influenced by factors like the particle's resistance to enzymatic degradation and the dynamic state of immune cells in the dermis.
Agglomeration and Encapsulation by Fibroblasts. Aggregated pigment particles can become encapsulated by fibroblasts, leading to the formation of a fibrotic capsule. This process contributes to the longevity and visibility of the pigment, as the encapsulated particles are mechanically isolated and immunologically concealed.
Integration into the Extracellular Matrix (ECM). Pigment particles may integrate into the ECM, where they can be physically trapped and biochemically anchored, further contributing to pigment stability and retention.

Over time, particles remaining in the dermis may be influenced by several additional factors that facilitate their eventual removal from the skin. The most prominent are the skin’s biochemical alterations, the body’s enzymatic activity, further immune responses, UV radiation, environmental factors, cell turnover, oxidative stress, chemical interactions, and exocytosis.