Same material, different reactions? Why PDO and PCL threads may seem fine while fillers can cause granulomas
Same material, different reactions? Why PDO and PCL threads may seem fine while fillers can cause granulomas
As the range of collagen-stimulating injectables grows, interest is also increasing in biodegradable polymers such as PDO (polydioxanone) and PCL (polycaprolactone).
Patients often ask: "Haven't PDO and PCL also been used in threads and sutures? Why can they cause granulomas when injected?"
This is a reasonable question. The key point is that the same material, or biodegradable polymers in the same family, do not always produce the same tissue response inside the body.
Tissue responses can be influenced not only by chemical composition but also by physical form, such as threads versus microparticles, particle size and surface characteristics, distribution within tissue, injection site and volume, and biodegradation.
This article examines how tissue responses may differ when PDO and PCL are used as threads or injectables, based on the literature reported to date.
Threads can also cause foreign body reactions
First, it is inaccurate to draw a simple distinction that "threads are safe and only injectables cause granulomas."
Absorbable threads, including PDO, are biomaterials implanted in the body and can cause foreign body reactions in surrounding tissue. Rare complications such as inflammatory nodules and foreign body granulomas have also been reported.
When foreign material enters the body, a series of foreign body reactions may occur to recognize and process it.
What matters, therefore, is assessing the following together, rather than simply whether a foreign body reaction is present.
- The physical form of the material introduced
- How it is distributed within tissue
- The degree of the reaction
- Whether the response stabilizes over time
- Whether it develops into a clinically evident inflammatory nodule or foreign body granuloma
The current literature does not allow a definitive direct comparison of PDO and PCL threads and injectables under identical conditions to conclude that "injectables have a higher granuloma incidence than threads."
However, even identical or similar polymers may produce different tissue responses depending on their formulation and how they exist within tissue.
An important distinction is formulation, as well as composition
Threads and microparticle injectables differ in how they exist within tissue.
PDO and PCL threads are inserted as continuous solid structures with a defined length and diameter.
In contrast, some injectables used to stimulate collagen disperse microparticles or microspheres throughout tissue.
A representative PCL-based filler consists of PCL microspheres suspended in a CMC (carboxymethylcellulose) gel carrier.
A study of a PCL-based filler reported a formulation containing PCL microspheres approximately 40 μm in size dispersed in a CMC gel carrier.
However, not all PDO and PCL injectables use the same particle size, shape, or carrier. The precise composition and formulation of each product must be checked individually.
These differences in physical structure can influence both material–tissue contact and the tissue responses involving macrophages, foreign body giant cells, and fibroblasts.
Why foreign body giant cells are seen around microparticles
When foreign material enters the body, macrophages recognize it and begin the process of removing or isolating it.
Around biomaterials whose size or shape makes them difficult for a single macrophage to process, several macrophages may fuse to form multinucleated foreign body giant cells.
These foreign body reactions can occur as various biomaterials interact with tissue.
An essential distinction is needed here. The presence of macrophages or foreign body giant cells in tissue alone does not establish that a clinical foreign body granuloma has developed.
With collagen-stimulating microparticle materials, cellular responses around the material, fibroblast activation, and collagen formation may occur together.
It is therefore necessary to distinguish a histological foreign body reaction around a biomaterial from a pathological foreign body granuloma associated with clinical problems such as persistent inflammation or nodules.
What tissue changes have been observed with PCL fillers?
Studies examining tissue after injection of PCL-based fillers have observed fibroblast accumulation and new collagen formation around PCL microspheres.
PCL microspheres therefore do more than occupy space: they interact with surrounding tissue and stimulate collagen formation.
Histological specimens may show foreign body responses, including macrophages or multinucleated foreign body giant cells, around spaces thought to have contained microspheres.
As explained above, however, these histological findings alone should not immediately be interpreted as a pathological granuloma.
The concern is when these reactions become excessive or persistent and lead to clinical symptoms such as the following.
- Firm, palpable nodules
- Recurrent or persistent swelling
- Redness
- Tenderness or pain
- Changes in the skin surface
It is therefore important to distinguish a histological foreign body reaction from a clinically problematic foreign body granuloma.
Microparticles also differ in surface area and distribution
Even with the same quantity of material, one continuous structure and a structure divided into many microparticles interact with tissue differently.
Threads lie continuously along a defined path, whereas microparticle injectables disperse many particles throughout the injection site.
The total area of material–tissue contact, the distribution pattern, and the way cells recognize the material may therefore differ.
Assessing tissue responses requires consideration not just of chemical composition, such as PDO versus PCL, but also material form, particle and surface characteristics, tissue distribution, and biodegradation.
Particle size and surface characteristics can also influence tissue responses
In biomaterials containing microparticles, particle size, shape, and surface characteristics can influence interactions between the material and tissue.
However, it is inappropriate to oversimplify this as "irregular particles cause granulomas" or "uniform particles do not cause granulomas."
A clinical foreign body granuloma is difficult to explain by a single cause.
Multiple factors may contribute, including the product's properties, injection site and volume, treatment technique, the patient's tissue and immune responses, and previous treatments.
Identifying the cause can be especially complex when several types of fillers or collagen-stimulating injectables have been repeatedly used in the same area.
Treatment technique is another important variable
With collagen-stimulating injectables, the tissue layer, volume, and injection technique are as important as the choice of product.
If a product is injected into an unsuitable location or an excessive amount is concentrated in one area, the possibility of localized nodules or uneven tissue responses must be considered.
Repeated injection of a new product into an area previously treated with other fillers or injectables may also leave several materials present together.
In such cases, symptoms alone may not identify which product or treatment is associated with a subsequent nodule or inflammation.
When a problem occurs after treatment, it is important to assess the products used, timing, injection sites and volumes, previous treatment history, and current clinical symptoms together, rather than attribute it to one particular ingredient.
This approach is not limited to PDO and PCL products.
With PDLLA (poly-D,L-lactic acid) collagen-stimulating injectables such as Juvelook, distinguishing the tissue response is also important when post-treatment nodules or inflammatory reactions become a concern.
In particular, when considering "Juvelook removal," rather than simply assuming that injected material remains,
first assess whether the palpable finding represents residual material, nodular changes, an inflammatory reaction, or changes associated with a foreign body granuloma.
The timing and number of previous treatments, injection sites, and other products used alongside them can also be important in determining the diagnosis and treatment approach.
What patterns have been reported for granulomas associated with collagen-stimulating fillers?
A systematic review published in the Journal of Cosmetic Dermatology in 2025 analyzed reported cases of foreign body granulomas following collagen-stimulating fillers.
The review included 40 studies describing 117 patients and reported foreign body granulomas associated with various materials, including PMMA, PLLA, CaHA, PCL, and dextran-based fillers.
Among the 117 reported cases, PMMA accounted for the largest share at 35.04%, followed by PLLA at 30.77%, CaHA at 27.35%, PCL at 4.27%, and dextran-based fillers at 2.56%.
There is, however, a very important caution when interpreting these figures.
These percentages are not incidence rates: they do not indicate what percentage of all patients treated with each product developed granulomas.
The study collected and analyzed cases in which foreign body granulomas had already occurred and been reported in the literature.
Moreover, most of the evidence consisted of case reports, and the authors explicitly noted that the available data could not establish the actual incidence for each filler.
Actual use volumes, duration of use, regional frequency of use, and reporting of adverse effects can also differ between products.
It would therefore be inaccurate to conclude from this study alone that "PCL has a granuloma incidence of 4.27%" or that "PCL carries a lower granuloma risk than other collagen stimulators."
More precisely, PCL-related cases made up a relatively small proportion of the reported foreign body granuloma cases included in that systematic review.
Ultimately, composition alone is not what matters
PDO and PCL are biodegradable polymers used in medical sutures and various biomaterials.
Even materials with the same composition or in the same family may contact and change within tissue differently when inserted as continuous threads versus dispersed as microparticles.
Tissue responses after treatment therefore do not depend simply on whether the material is PDO or PCL.
Multiple factors must be considered together: formulation and particle characteristics, tissue distribution, injection site and volume, biodegradation, repeated treatments, and each patient's tissue and immune responses.
It is also necessary to distinguish macrophage or foreign body giant cell responses around biomaterials from foreign body granulomas associated with clinical symptoms such as persistent inflammation or nodules.
It is therefore inappropriate to conclude simply that "it must be safe because it is also used in sutures" or, conversely, "it is a dangerous material because granuloma cases have been reported."
Before treatment, it is important to confirm the product's exact composition and formulation, approval status and indications in Korea, and to develop an appropriate treatment plan based on its characteristics.
If firm nodules, recurrent swelling, redness, or pain have already developed after treatment, assessment is needed to distinguish simple product accumulation, inflammatory nodules, and delayed foreign body reactions, including foreign body granulomas.
Particularly after repeated treatments with several fillers or collagen-stimulating injectables, establishing which products were used, when, and where may be important in determining the diagnosis and treatment approach.
If you are concerned about facial foreign material or filler granulomas, contact 02-545-3700 or "UVOM Plastic Surgery" on KakaoTalk.
For more columns on facial foreign material removal, select a title below ▼
How can an unknown substance injected into the face long ago be identified?
Can all the filler remaining from an earlier treatment be removed?
Why tissue around facial foreign material becomes firm
Can granulomas develop years after filler treatment?
References
Wang H, Wu D, Lo C, Liu S, Ji Q, Reem A-A, Qiu H. Foreign Body Granulomas Reaction Related to Collagen Stimulatory Cosmetic Fillers: A Systematic Review. Journal of Cosmetic Dermatology. 2025;24(10). doi:10.1111/jocd.70459.
Kim JA, Van Abel D. Neocollagenesis in Human Tissue Injected With a Polycaprolactone-Based Dermal Filler. Journal of Cosmetic and Laser Therapy. 2015;17(2):99-101.
Kim JS. Changes in Dermal Thickness in Biopsy Study of Histologic Findings After a Single Injection of Polycaprolactone-Based Filler Into the Dermis. Aesthetic Surgery Journal. 2019;39(12).