2026-10-29
The Truth About Injection Procedures: Fillers, Biostimulants, and ECM (ADM) Skin Boosters Through an Immunological Lens
Explains how immune responses shape the results and side effects of injectables, including filler nodules, swelling, and ECM (ADM) skin booster absorption.
Hello.
This is Snu Plastic Surgery Clinic.
As a plastic surgeon, this is how I see injection procedures.
"Any foreign material that enters the body will always be recognized by immune cells, which will try to engulf it and break it down."
Many people say HA fillers are fine because hyaluronidase dissolves them in the end.
But hyaluronidase is ultimately just one of the tools immune cells use to process foreign material.
When filler particles are heavily cross-linked or the amount is too large, immune cells cannot easily clear them. More immune cells then gather, carry the material toward the lymph nodes, and the body breaks it down biologically in the process.
📍This is also why nodules can form in unexpected places.
Let's take a simple look at the effects and side effects of injection procedures through the single lens of the immune response.
1. Whatever Goes into the Body, Immune Cells Rush In First
When any substance enters the skin, the body recognizes it as an invader.
Immune cells such as neutrophils, monocytes, and macrophages gather to try to engulf the foreign material, and as fibroblasts become activated, collagen accumulates.
This is not a pathological process. It is a normal response in which the body tries to contain the foreign material.
Problems arise when the material is too large or too complex for immune cells to handle properly.
With HA fillers too, the more complexly the particles are cross-linked, the harder it becomes for macrophages to engulf them. They remain in tissue longer, continuously stimulating the immune system.
Some studies show that HA itself does not trigger a strong immune response. However, because HA can help support immune reactions, the response can intensify when it overlaps with bacterial stimulation or systemic inflammation.
2. Undissolved Foreign Material Travels to the Lymph Nodes
If macrophages cannot fully process the foreign material, immune cells carry it through the lymphatic vessels to the lymph nodes.
Because fillers lack a firm barrier like a synthetic implant, they can spread along surrounding lymphatic vessels and soft tissue.
✨For this reason, filler migration is mainly explained as movement through the lymphatic system.
In this process, cases have been reported in which lymph nodes become swollen or compressed. Localized blockage of lymphatic vessels can also cause swelling and inflammation to persist for a long time.
Nodules forming in unexpected places is not simply due to pressure. It is the result of immune cells actively transporting the foreign material.
3. The Hidden Driver of Injection Results: Swelling and Fluid Shifts
The "volume" from an injection procedure cannot be explained by the amount of material injected alone.
Fluid shifts driven by the immune response play a major role.
HA has a water-attracting property, so it draws in surrounding moisture and increases volume.
In addition, when an immune response occurs, local blood flow increases and exudate forms, causing temporary swelling.
At a moderate level, this creates natural-looking volume. When excessive, however, it can show up as severe swelling, frequent puffiness, or delayed edema.
📍Residual filler can remain in tissue for years and may even contribute to chronic inflammation.
4. The Three-Part Effect Set: Side Effects Also Start Here
The volume effect of injection procedures is largely the sum of three components.
1. The actual volume of the injected material 2. Fluid shifts (swelling) caused by the immune response 3. Granulation tissue formed by the immune response, the process manufacturers call "collagen neogenesis"
When the immune response is appropriate, it leads to tissue regeneration and collagen deposition. When the response is excessive or uncontrolled, however, it can progress to nodules (granulomas) or chronic edema.
📌Apart from bacterial infections, most complications of injection procedures can be explained within this immune-response framework.
5. Each Material Triggers a Different Response: HA Filler, PLLA, CaHA, ECM (ADM), Botulinum Toxin, and Rejuran
HA Filler |
HA is naturally found in the body and increases volume by attracting water. Because of this, many assume it can simply be dissolved with hyaluronidase. But dissolving it is also part of how immune cells process foreign material. When the crosslinks are complex or the amount is large, immune cells cannot easily clear the filler, so it stays in tissue longer. This can lead to swelling, delayed edema, nodules, and migration toward the lymph nodes. 📌HA fillers are not outside the framework of the immune response either. |
PLLA (Sculptra and similar products) |
Its particles are irregular and less uniform, so they attract more immune cells and stimulate collagen production through inflammatory pathways. Because its effects are strong, its inflammatory response is also relatively pronounced. |
CaHA (Radiesse and similar products) |
Its particles are smooth and uniform, so the initial inflammatory response is relatively mild. Some explain that it works toward regeneration through physical stimulation, but that does not mean there is no immune response at all. |
ECM Skin Boosters and ADM Powder |
They are promoted as "human-derived collagen" with "almost no immune reaction," but once injected as fine particles, it is difficult to avoid a foreign-body reaction in the broader sense. They typically show absorption within 3 to 6 months. However, this "absorption" is not simple disappearance. It is a biological process in which immune cells process the particles and granulation tissue and collagen fill the space. 📌If particles clump together or the immune response becomes excessive during absorption, nodules can form. In one study that used micronized ADM together with HA filler, temporary subcutaneous nodules were reported. Granulomas caused by foreign-body reactions have also been reported when ADM is used surgically. |
Botulinum Toxin and Rejuran (Polynucleotide) |
These work mainly through pharmacological action and do not occupy volume over the long term. They differ from fillers and biostimulants, which remain in the body as foreign material and sustain immune responses. 📌From an immunological standpoint, these are exceptional injection procedures. |
Closing Thoughts: Injection Procedures Are Not a Cure-All
📍Injection procedures are useful tools, but they are not a cure-all.
Any substance that enters the body becomes a target of the immune response, and the intensity and pattern of that response determine the difference between results and side effects.
✨Breakdown of HA fillers is not simply chemical degradation. It is a biological process driven by immune cells, and nodules and swelling are part of that same continuum.
✨ECM (ADM) skin boosters also show absorption within 3 to 6 months. Because that absorption is itself the immune cells' processing of the material, the possibility of nodules must be kept in mind.
📌For this reason, long-lasting fillers, body and cranial fillers injected in large volumes, biostimulants such as PLLA and CaHA, and ECM (ADM) skin boosters should be approached only with a full understanding of their properties and immunological implications.
When we understand the immune-response reality behind claims like "it lasts a long time," "it builds new collagen," and "it's fine because it gets absorbed," we can deliver procedures that are more honest and safer for patients.
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Frequently Asked Questions
Why can fillers form nodules in unexpected places?
The article explains that this is because immune cells carry the foreign material along the lymphatic vessels toward the lymph nodes. Since fillers lack a firm barrier, they can spread along surrounding lymphatic vessels and soft tissue. Nodules can therefore be seen as the result of this active transport process, not pressure alone.
Is it safe to dissolve HA fillers with hyaluronidase?
The article explains that dissolving filler with hyaluronidase is itself part of how immune cells process foreign material. It therefore cautions against feeling reassured simply because the filler can be dissolved. When the crosslinks are complex or the amount is large, immune cells struggle to clear it, and it may remain in tissue for a long time.
Are ECM (ADM) skin boosters fine because they get absorbed?
The article explains that ECM (ADM) skin boosters typically show absorption within 3 to 6 months, but absorption alone does not make them definitively safe. Absorption is the process by which immune cells break down the particles and granulation tissue and collagen fill the space. Nodules can form if the particles clump together or the reaction becomes excessive.
Do PLLA and CaHA trigger the same level of immune response?
No. According to the article, PLLA attracts more immune cells and produces a relatively stronger inflammatory response, while CaHA has a relatively mild initial inflammatory response. However, the article notes that CaHA still does not avoid an immune response altogether.
What determines the volume effect of injection procedures?
The article explains that injection volume is the combined result of the actual volume of the injected material, fluid shifts (swelling) caused by the immune response, and granulation tissue formation. HA has the property of drawing in surrounding water to increase volume, and excessive fluid shifts can appear as severe swelling or delayed edema.
How do botulinum toxin and Rejuran differ from fillers?
The article explains that botulinum toxin and Rejuran differ from fillers in that their main mechanism is pharmacological action and they do not occupy volume over the long term. They are regarded as distinct from fillers and biostimulants, which remain as foreign material and sustain an immune response.