The Biology of Facial Fillers

Stuart H Bentkover

doi:10.1055/s-0029-1220646

Facial Plastic Surgery, Table of Contents

Facial Plast Surg 2009; 25(2): 073-085
DOI: 10.1055/s-0029-1220646

The Biology of Facial Fillers

Stuart H. Bentkover¹

¹Bentkover Facial Plastic Surgery and Laser Center, Worcester, Massachusetts; Clinical Instructor, Department of Otology and Laryngology, Harvard Medical School, Boston, MA

Abstract

ABSTRACT

The biologic behavior of a facial filler determines its advantages and disadvantages. The purpose of this article is to look at the relevant biology as part of a logical basis for making treatment decisions. Historical perspectives and biologic characteristics such as local tissue reaction (including phagocytosis and granulomatous inflammation) cross-linking, particle concentration, immunogenicity, biofilm formation, gel hardness, and collagen neogenesis are considered. Bovine collagen is the most immunogenic facial filler. Porcine and bioengineered human collagen implants have very low immunogenicity, but allergic reactions and elevations of IgG are possible. Cross-linking and concentration affect the longevity of collagen and hyaluronic acid fillers. Gel hardness affects how a hyaluronic acid filler flows through the syringe and needle. Calcium hydroxylapatite, poly-L-lactic acid, and polymethylmethacrylate fillers have been shown to stimulate collagen neogenesis. It appears that any facial filler can form a granuloma. Bacterial biofilms may play a role in the activation of quiescent granulomas. Various authors interpret the definition and significance of a granuloma differently.

KEYWORDS

Facial filler - phagocytosis - granuloma - cross-linking - immunogenicity - biofilm - collagen neogenesis

Full Text

References

REFERENCES

1 Rohrich RJ Semipermanent and permanent dermal/subdermal fillers supplement. Plast Reconstr Surg 2006;118(3S)1S–84S
2 Bader R S, Johnson D L. Dermal fillers. Available at: http://emedicine.medscape.com Accessed November 1, 2008
3 Carruthers J. Review of long-lasting dermal fillers. Available at: http://www.Miinews.com Accessed November 1, 2008
4 Kumar V, Cotran R S, Robbins S L. Robbins Basic Pathology. 7th ed. Philadelphia, PA; Saunders 2003: 41-42, 56
5 Rubin E, Farber J L. Pathology. 3rd ed. Philadelphia, PA; Lippincott-Raven 1999 62-67 72-73
6 Broder K W, Cohen S R. An overview of permanent and semipermanent fillers. Plast Reconstr Surg. 2006; 118(3S) 7S-14S
7 Champion J A, Walker A, Mitragotri S. Role of particle size in phagocytosis of polymeric microspheres. Pharm Res. 2008; 25 1815-1821
8 Champion J A, Mitragotri S. Role of target geometry in phagocytosis. Proc Natl Acad Sci U S A. 2006; 103 4930-4934
9 Champion J, Mitragotri S. Recognition of the size of polymer drug carriers by macrophages. Available at: http://aiche.confex.com/aiche/2006/techprogram/P66762.HTM Accessed December 13, 2008
10 Freitas Jr R A. Alumina and sapphire particles. NanomedicineBookSite. Available at: http://www.nanomedicine.com/NMIIA/15.3.5.5.htm Accessed December 13, 2008
11 Morhenn V B, Lemperle G, Gallo R L. Phagocytosis of different particulate dermal filler substances by human macrophages and skin cells. Dermatol Surg. 2002; 28 484-490
12 Ishikawa Y, Muramatsu N, Ohshima H, Kondo T. Effect of particle size on phagocytosis of latex particles by guinea-pig polymorphonuclear leucocytes. J Biomater Sci Polym Ed. 1991; 2 53-60
13 Chen H, Langer R, Edwards D A. A film tension theory of phagocytosis. J Colloid Interface Sci. 1997; 190 118-137
14 Tomazic-Jezic V J, Merritt K, Umbreit T H. Significance of the type and size of biomaterial particles on phagocytosis and tissue distribution. J Biomed Mater Res. 2001; 55 523-529
15 DeLustro F, Smith S T, Sundsmo J, Salem G, Kincaid S, Ellingsworth L. Reaction to injectable collagen: results in animal models and clinical use. Plast Reconstr Surg. 1987; 79 581-594
16 Frank D H, Vakassian L, Fisher J CMD, Ozkan N. Human antibody response following multiple injections of bovine collagen. Plast Reconstr Surg. 1991; 87 1080-1088
17 Cukier J, Beauchamp R A, Spindler J S, Lorenzo C, Rentham D E. Association between bovine collagen dermal implants and a dermatomyositis or a polymyositis-like syndrome. Ann Intern Med. 1993; 118 920-928
18 Moscona R R, Bergman R, Friedman-Birnbaum R. An unusual late reaction to Zyderm I injections: a challenge for treatment. Plast Reconstr Surg. 1993; 92 331-334
19 Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg. 2005; 29 34-48
20 Christensen L. Normal and pathologic tissue reactions to soft tissue gel filers. Dermatol Surg. 2007; 33(Suppl 2) S168-S175
21 Bucalo L R, Schwendner S, Wirtz U F, Sreedharan S, Bernstein L R. Use of gallium to treat biofilm-associated infections. World Intellectual Property Organization. Available at: http://www.wipo.int/pctdb/en/wo.jsp?WO=2007087461 Accessed November 15, 2008
22 Hall-Stoodley L, Ze F H, Gieseke A et al.. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA. 2006; 296 202-211
23 Barakate M, Bekenham E, Curotta J, da Crua M. Bacterial biofilm adherence to middle-ear ventilation tubes: scanning electron micrograph images and literature review. J Laryngol Otol. 2007; 121 993-997
24 Tezel A, Fredrickson G H. The science of hyaluronic acid dermal fillers. J Cosmet Laser Ther. 2008; 10 35-42
25 Wang F, Garza L A, Kang S et al.. In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol. 2007; 143 155-163
26 Webster R C, Fuleihan N S, Gaunt J, Hamdan U S, Smith R C. Injectable silicone for small augmentations: twenty year experience in humans. Am J Cosmet Surg. 1984; 1 1-10
27 Webster R C, Gaunt J M, Hamdan U S, Fuleihan N S, Smith R C. Injectable silicone for facial soft-tissue augmentation. Arch Otolaryngol Head Neck Surg. 1986; 112 290-296
28 Orentreich N O. Soft tissue augmentation with medical-grade fluid silicone. In: Rubin LR Biomaterials in Reconstructive Surgery. St. Louis, MO; Mosby 1983: 859-881
29 Orentreich D S, Orentreich N. Injectable fluid silicone. In: Roenigk RK, Roenigk HH Dermatologic Surgery: Principles and Practice. New York, NY; Marcel Dekker 1989: 1349-1395
30 Narins R S, Beer K. Liquid injectable silicone: a review of its history, immunology, technical considerations, complications, and potential. Plast Reconstr Surg. 2006; 118(3S) 77S-84S
31 Tilleman T R. Cosmetic use of injection silicone oils; approved material with unapproved procedure. Time to ban “off-label” use? Paper submitted in satisfaction of course requirement and MPA/MC reading and research requirement. Food and drug law. Professor Peter Barton Hutt. January 2005 Harvard Law School, Cambridge, MA;
32 Kamer F M, Churukian M M. Clinical use of injectable collagen. Arch Otolaryngol. 1984; 110 93-98
33 Homicz M R, Watson D. Review of injectable materials for soft tissue augmentation. Facial Plast Surg. 2004; 20 21-29
34 Bailey A J. The fate of collagen implants in tissue defects. Wound Repair Regen. 2000; 8 5-12
35 Webster R C, Kattner M D, Smith R C. Injectable collagen for augmentation of facial areas. Arch Otolaryngol. 1984; 110 652-656
36 Knapp T R, Kaplan E N, Daniels J R. Injectable collagen for soft tissue augmentation. Plast Reconstr Surg. 1977; 60 398-405
37 Narins R S, Frandt F S, Lorenc Z P, Mass C S, Monheit G D, Smith S R. 12 month persistency of a novel ribose-cross-linked collagen dermal filler. Dermatol Surg. 2008; 34(Suppl 1) S31-S39
38 Shoshani D, Markovitz E, Cohen Y, Heremans A, Goldlust A. Skin test hypersensitivity study of a cross-linked, porcine collagen implant for aesthetic surgery. Dermatol Surg. 2007; 33(Suppl 2) S152-S158
39 Monstrey S J, Pitaru S D, Moustapha H et al.. A two-stage trial of Evolence30 collagen for soft-tissue contour correction. Plast Reconstr Surg. 2007; 120 303-311
40 Narins R S, Frandt F S, Lorenc Z P et al.. A randomized, multicenter study of the safety and efficacy of Dermicol-P35 and non-animal stabilized hyaluronic acid gel for the correction of nasolabial folds. Dermatol Surg. 2007; 33(Suppl 2) S213-S221
41 Sclafani A P, Romo III T. Collagen, human collagen, and fat: the search for a three-dimensional soft tissue filler. Facial Plast Surg. 2001; 17 79-85
42 Stolman L P. Human collagen reactions. Dermatol Surg. 2005; 31 1634
43 Arron S T, Neuhaus I M. Persistent delayed-type hypersensitivity reaction to injectable non-animal-stabilized hyaluronic acid. J Cosmet Dermatol. 2007; 6 167-171
44 Friedman P M, Mafong E A, Kauvar A N, Geronemus R G. Safety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation. Dermatol Surg. 2002; 28 491-494
45 Vartanian A J, Frankel A S, Rubin M G. Injected hyaluronidase reduces Restylane-mediated cutaneous augmentation. Arch Facial Plast Surg. 2005; 7 231-237
46 Soparkar C NS, Patrinely J R, Skibell B C, Tower R N. Hyaluronidase and Restylane. Arch Facial Plast Surg. 2007; 9 299-300
47 Sall I, Ferard G. Comparison of the sensitivity of 11 crosslinked hyaluronic acid gels to bovine testis hyaluronidase. Polym Degrad Stab. 2007; 92 915-919
48 Macready N. Dermal fillers: focus on hyaluronic acid. Presented at: American Society of Aesthetic Plastic Surgery Meeting May 1–7, 2008 San Diego, CA; Available at: http://www.medscape.com/viewarticle/576776 Accessed December 12, 2008
49 Arlette J P, Trotter M J. Anatomic location of hyaluronic acid filler material injected into the nasolabial fold: a histologic study. Dermatol Surg. 2008; 34(Suppl 1) S56-S63
50 Costantino P D, Friedman C D, Lane A. Synthetic biomaterials in facial plastic and reconstructive surgery. Facial Plast Surg. 1993; 9 1-15
51 Berlin A L, Hussain M, Goldberg D J. Calcium hydroxylapatite filler for facial rejuvenation: a histologic and immunohistochemical analysis. Dermatol Surg. 2008; 34(Suppl 1) S64-S67
52 Sadick N S, Katz B E, Deborshi R. A multicenter, 47-month study of safety and efficacy of calcium hydroxylapatite for soft tissue augmentation of nasolabial folds and other areas of the face. Dermatol Surg. 2007; 33(Suppl) S122-S127
53 Carruthers A, Liebeskind M, Carruthers J, Foster B B. Radiographic and computed tomographic studies of calcium hydroxylapatite for treatment of HIV-associated facial lipoatrophy and correction of nasolabial folds. Dermatol Surg. 2008; 34(Suppl) S78-S84
54 Tzikas T L. Evaluation of the Radiance FN soft tissue filler for facial soft tissue augmentation. Arch Facial Plast Surg. 2004; 6 234-239
55 Marmur E S, Phelps R, Goldberg D. Clinical, histologic and electron microscopic findings after injection of a calcium hydroxylapatite filler. J Cosmet Laser Ther. 2004; 6 223-226
56 Holzapfel A M, Mangat D S, Barron D S. Soft-tissue augmentation with calcium hydroxylapatite: histological analysis. Arch Facial Plast Surg. 2008; 10 335-338
57 Jansen D A, Graivier M H. Evaluation of a calcium hydroxylapatite-based implant (Radiesse) for facial soft-tissue augmentation. Plast Reconstr Surg. 2006; 118(3S) 22S-30S
58 Sankar V, McGuff H S. Foreign body reaction to calcium hydroxylapatite after lip augmentation. J Am Dent Assoc. 2007; 138 1093-1096
59 Lam S M, Azizzadeh B, Graivier M. Injectable poly-l-lactic acid (Sculptra): technical considerations in soft-tissue contouring. Plast Reconstr Surg. 2006; 118(3S) 55S-63S
60 Humble G, Mest D. Soft tissue augmentation using Sculptra. Facial Plast Surg. 2004; 20 157-163
61 Dermik, Inc. NEW-FILL^®. Sculpting and filling innovation. Available at: http://www.i-base.info/i-basemeetings/lipo/Mediphi63l%20doctors%20training.ppt Accessed December 12, 2008
62 Vleggaar D. Soft-tissue augmentation and the role of poly-l-lactic acid. Plast Reconstr Surg. 2006; 118(3S) 46S-54S
63 Fulton JE Jr, Porumb S, Caruso J, Shitabata P. Lip augmentation with liquid silicone. Dermatol Surg. 2005; 31 1577-1585
64 Cohen S R, Berner C F, Busso M et al.. ArteFill: a long-lasting injectable wrinkle filler material – Summary of the U.S. Food and Drug Administration trials and a progress report on 4- to 5-year outcomes. Plast Reconstr Surg. 2006; 118(3S) 64S-76S
65 Judet J. Prostheses en resins acrylic. Mem Acad Chir (Paris). 1947; 73 561
66 Alam M, Gladstone H, Kramer E M et al.. ASDS guideline of care: injectable fillers. Dermatol Surg. 2008; 34(Suppl 1) S115-S148
67 Lemperle G, Ott H, Charrier U, Hecker J, Lemperle M. PMMA microspheres for intradermal implantation, part I: animal research. Ann Plast Surg. 1991; 26 57-62
68 Bagal A, Dahiya R, Tsai V, Adamson P. Clinical experience with polymethylmethacrylate microspheres (Artecoll) for soft-tissue augmentation. A retrospective review. Arch Facial Plast Surg. 2007; 9 275-280
69 McClelland M, Egbert B, Hanko V, Berg R A, DeLustro F. Evaluation of Artecoll polymethylmethacrylate implant for soft-tissue augmentation: biocompatibility and chemical characterization. Plast Reconstr Surg. 1997; 100 1466-1474
70 Reisberger E M, Landthaler M, Luitgard W, Schröder Stolz W. Foreign body granulomas caused by polymethylmethacrylate microspheres. Successful treatment with allopurinol. Arch Dermatol. 2003; 139 17-20
71 Salles A G, Lotierzo P H, Gemperli R et al.. Complications after polymethylmethacrylate injections: report of 32 cases. Plast Reconstr Surg. 2008; 121 1811-1820
72 Van de Belt H, Neut D, Schenk W, van Horn J R, van der Mei H C, Busscher H J. Infection of orthopedic implants and the use of antibiotic-loaded bone cements. Acta Orthop Scand. 2001; 72 557-571

Stuart H BentkoverM.D. F.A.C.S.

Bentkover Facial Plastic Surgery and Laser Center

123 Summer Street, Suite 675, Worcester, MA 01608

Email: stuart.bentkover@drbentkover.com