Alijotas-Reig J, Fernández-Figueras MT, Puig L. Late-onset inflammatory adverse reactions related to soft tissue filler injections. Clin Rev Allergy Immunol. 2013; 45:(1)97-108

Alijotas-Reig J, Esteve-Valverde E, Gil-Aliberas N Autoimmune/inflammatory syndrome induced by adjuvants-ASIA-related to biomaterials: analysis of 45 cases and comprehensive review of the literature. Immunol Res. 2018; 66:(1)120-140

Artzi O, Cohen JL, Dover JS Delayed inflammatory reactions to hyaluronic acid fillers: a literature review and proposed treatment algorithm. Clin Cosmet Investig Dermatol. 2020; 13:371-378

Bachour Y, Kadouch JA, Niessen FB. The aetiopathogenesis of late inflammatory reactions (LIRs) after soft tissue filler use: a systematic review of the literature. Aesthetic Plast Surg. 2021; 45:(4)1748-1759

Barone DG, Carnicer-Lombarte A, Tourlomousis P Prevention of the foreign body response to implantable medical devices by inflammasome inhibition. Proc Natl Acad Sci U S A. 2022; 119:(12)

Bell T, Kelso K. Hyaluronic acid dermal fillers and autoimmune disorders: a case report and discussion of a late-onset complication. J Aes Nurs. 2021; 10:28-33

Bomford R. Will adjuvants be needed for vaccines of the future?. Dev Biol Stand. 1998; 92:13-7

Breithaupt A, Fitzgerald R. Collagen stimulators: poly-L-Lactic acid and calcium hydroxyl apatite. Facial Plast Surg Clin North Am. 2015; 23:(4)459-69

Carruthers JD, Carruthers JA, Humphrey S. Fillers and neocollagenesis. Dermatol Surg. 2014; 40:S134-6

Cabral LRB, Teixeira LN, Gimenez RP Effect of hyaluronic acid and poly-L-Lactic acid dermal fillers on collagen synthesis: an in vitro and in vivo study. Clin Cosmet Investig Dermatol. 2020; 13:701-710

Choi MS, Kwak S, Kim J Comparative analyses of inflammatory response and tissue integration of 14 hyaluronic acid-based fillers in mini pigs. Clin Cosmet Investig Dermatol. 2021; 14:765-778

Coleman KM, Voigts R, DeVore DP Neocollagenesis after injection of calcium hydroxylapatite composition in a canine model. Dermatol Surg. 2008; 34:S53-5

Contesini N, Adami F, Blake Md Nutritional strategies of physically active subjects with muscle dysmorphia. Int Arch Med. 2013; 6:(1)

Chung L, Maestas DR, Housseau F Key players in the immune response to biomaterial scaffolds for regenerative medicine. Adv Drug Deliv Rev. 2017; 114:184-192

Courderot-Masuyer C, Robin S, Tauzin H Evaluation of lifting and antiwrinkle effects of calcium hydroxylapatite filler. In vitro quantification of contractile forces of human wrinkle and normal aged fibroblasts treated with calcium hydroxylapatite. J Cosmet Dermatol. 2016; 15:(3)260-8

de Almeida AT, Figueredo V, da Cunha ALG Consensus recommendations for the use of hyperdiluted calcium hydroxyapatite (radiesse) as a face and body biostimulatory agent. Plast Reconstr Surg Glob Open. 2019; 7:(3)

Decates T, Kadouch J, Velthuis P Immediate nor delayed type hypersensitivity plays a role in late inflammatory reactions after hyaluronic acid filler injections. Clin Cosmet Investig Dermatol. 2021; 14:581-589

Decates TS, Velthuis PJ, Schelke LW Increased risk of late-onset, immune-mediated, adverse reactions related to dermal fillers in patients bearing HLA-B*08 and DRB1*03 haplotypes. Dermatol Ther. 2021; 34:(1)

Dimatteo R, Darling NJ, Segura T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv Drug Deliv Rev. 2018; 127:167-184

El-Khalawany M, Fawzy S, Saied A Dermal filler complications: a clinicopathologic study with a spectrum of histologic reaction patterns. Ann Diagn Pathol. 2015; 19:(1)10-5

Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007; 127:(3)514-25

Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013; 6:295-316

Graivier MH, Bass LM, Lorenc ZP Differentiating non Permanent injectable fillers: prevention and treatment of filler complications. Aesthet Surg J. 2018; 38:S29-S40

Griffin DR, Archang MM, Kuan CH Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing. Nat Mater. 2021; 20:(4)560-569

Huyer LD, Pascual-Gil S, Wang Y Advanced strategies for modulation of the material-macrophage interface. Adv. Funct. Mater. 2020; 30:(44)

Julier Z, Park AJ, Briquez PS Promoting tissue regeneration by modulating the immune system. Acta Biomater. 2017; 53:13-28

Kontis TC, Rivkin A. The history of injectable facial fillers. Facial Plast Surg. 2009; 25:(2)67-72

Krafts KP. Tissue repair: the hidden drama. Organogenesis. 2010; 6:(4)225-33

Larouche J, Sheoran S, Maruyama K Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv Wound Care (New Rochelle). 2018; 7:(7)209-231

Lee JM, Kim YJ. Foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. Arch Plast Surg. 2015; 42:(2)232-9

Lemperle G. Update on 2003 article “human histology and persistence of various injectable filler substances for soft tissue augmentation”. Aesthetic Plast Surg. 2020; 44:(4)1361-1363

Lemperle G, Gauthier-Hazan N, Wolters M Foreign body granulomas after all injectable dermal fillers: part 1. Possible causes. Plast Reconstr Surg. 2009; 123:(6)1842-1863

Loghem JV, Draoui O, Peters W The story of calcium hydroxylapatite. In “calcium hydroxylapatite soft tissue fillers: expert treatment techniques”, 1st ed. : CRC Press; 2021

Loghem JV, Yutskovskaya YA, Philip WW. Calcium hydroxylapatite: over a decade of clinical experience. J Clin Aesthet Dermatol. 2015; 8:(1)38-49

Mariani E, Lisignoli G, Borzì RM Biomaterials: foreign bodies or tuners for the immune response?. Int J Mol Sci. 2019; 20:(3)

Nicolau PJ. Long-lasting and permanent fillers: biomaterial influence over host tissue response. Plast Reconstr Surg. 2007; 119:(7)2271-2286

Nowag B, Casabona G, Kippenberger S Calcium hydroxylapatite microspheres activate fibroblasts through direct contact to stimulate neocollagenesis. J Cosmet Dermatol. 2022;

Pavicic T. Complete biodegradable nature of calcium hydroxylapatite after injection for malar enhancement: an MRI study. Clin Cosmet Investig Dermatol. 2015; 8:19-25

Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012; 49:(1)35-43

Shoenfeld Y, Agmon-Levin N. ‘ASIA’ - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011; 36:(1)4-8

Stein P, Vitavska O, Kind P The biological basis for poly-L-lactic acid-induced augmentation. J Dermatol Sci. 2015; 78:(1)26-33

Takeo M, Lee W, Ito M. Wound healing and skin regeneration. Cold Spring Harb Perspect Med. 2015; 5:(1)

Vleggaar D. Facial volumetric correction with injectable poly-L-lactic acid. Dermatol Surg. 2005; 31:(11 Pt 2)1511-7

Wang F, Garza LA, Kang S In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol. 2007; 143:(2)155-163

Watad A, Sharif K, Shoenfeld Y. The ASIA syndrome: basic concepts. Mediterr J Rheumatol. 2017; 28:(2)64-69

Wilgus T. Fetal wound healing. In: Das A, Debasis B, Sashwathi R. United Kingdom: Elsevier Science; 2020

The dichotomy of dermal fillers: when does the biostimulatory response become one of regeneration versus one of replacement?

02 July 2023
Volume 12 · Issue 6


Many dermal fillers are classified as biostimulatory, meaning they stimulate the dermis to create new collagen, elastin, and other components of the extracellular matrix. Normal wound healing is also a biostimulatory process. It can be one of tissue replacement with scar formation, or one of true regenerative healing with functional restoration of the tissue. Dermal fillers can stimulate both types of healing, but to different degrees. This paper reviews this mechanism, exploring why some fillers seem to favour replacement, and some true regeneration. The patient's and the filler's propensity for late inflammatory reactions and their relationship to the biostimulatory characteristics of the product are examined as well.

Since the advent of injectable dermal fillers, the quest for the perfect filler has been a lofty goal. The perfect filler would integrate smoothly into tissue, cause minimal oedema and inflammation, be easily reversible, be devoid of any type of foreign body response, be non-allergenic, be stable and predictable, breaking down into to nonimmunogenic particles and be naturally absorbed or dissolved without incident. Unfortunately, such a filler does not exist. Since the Food and Drug Administration's (FDA) approval of injectable bovine collagen in the early 1980s, dozens of injectable filling agents have been developed; but history has taught us that new technologies must be used with care because complications can occur, sometimes many years after treatment (Kontis and Rivkin, 2009). Dermal fillers are no exception. While the vast majority of patients have good outcomes, late onset adverse reactions have been reported with all the available products on the market.

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