Abstract
An increasing number of soft tissue filler substances have been introduced to the beauty market outside the U.S. which lack experimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test sites were excised, histologically examined, and graded according to foreign body reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had encapsulated with connective tissue, macrophages, and sporadic giant cells. Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the tissue, causing a chronic foreign body reaction. Polylactic acid microspheres (New-Fill) induced a mild inflammatory response and had disappeared clinically at 4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body reaction and had disappeared at 6 months. Polymethylacrylate particles (Dermalive) induced the lowest cellular reaction but had disappeared clinically at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to a lessening degree over the entire testing period. Histologically, it dissipated more slowly and was kept in place through fine fibrous capsules. Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres (Radiance FN) induced almost no foreign body reaction but were absorbed by the skin at 12 months.
Host defense mechanisms react differently to the various filler materials, but all substances—resorbable or nonresorbable—appeared to be clinically and histologically safe, although all exhibit undesirable side effects. Since the mechanism of late inflammation or granuloma formation is still unknown, early histological findings are not useful in predicting possible late reactions to filler substances.
Similar content being viewed by others
References
TS Alster TB West (2000) ArticleTitleHuman-derived and new synthetic injectable materials for soft-tissue augmentation: Current status and role in cosmetic surgery. Plast Reconstr Surg 105 2515
P Amard (2001) ArticleTitlePLA (New-Fill) as management of lipoatrophy of the face. Magazin Aesthet Surg 1 28
KA Athanasiou GG Niederauer CM Agrawal A Landsman (1995) ArticleTitleApplications of biodegradable lactides and glycolides in pediatry. Implant Biomater 12 475 Occurrence Handle1:STN:280:BymD3M3ls1A%3D
M Bendszus R Klein R Burger et al. (2000) ArticleTitleEfficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of meningiomas. Am J Neurorad 21 255 Occurrence Handle1:STN:280:DC%2BD3c7lvVGmsA%3D%3D Occurrence Handle10696005
AE Bent J Foote S Siegel G Faerber R Chao EA Gormley (2001) ArticleTitleCollagen implant for treating stress urinary incontinence in women with urethral hypermobility. J Urol 166 1354 Occurrence Handle1:STN:280:DC%2BD3MrhvVWrtQ%3D%3D Occurrence Handle11547073
C Bergeret-Galley X Latouche Y-G Illouz (2001) ArticleTitleThe value of new filler material in corrective and cosmetic surgery: DermaLive and DermaDeep. Aesth Plast Surg 25 249 Occurrence Handle10.1007/s002660010131
X Bigata M Ribera I Bielsa C Ferrandiz (2001) ArticleTitleAdverse granulomatous reaction after cosmetic dermal silicone injection. Dermatol Surg 27 198 Occurrence Handle10.1046/j.1524-4725.2001.00020.x Occurrence Handle1:STN:280:DC%2BD3MzjvVemsQ%3D%3D Occurrence Handle11207699
S Burres (1996) ArticleTitleRecollagenation of acne scars. Dermatol Surg 22 364 Occurrence Handle10.1016/1076-0512(95)00582-X Occurrence Handle1:STN:280:BymB3MvgvVM%3D Occurrence Handle8624662
M Busso (2003) ArticleTitleSoft tissue augmentation with Radiance FN. Aesthetic Trends & Technologies 2 IssueID3 .
KV Cahill JA Burns (1989) ArticleTitleVolume augmentation of the anophthalmic orbit with cross-linked collagen (Zyplast). Arch Ophthalmol 107 1684 Occurrence Handle1:STN:280:By%2BD2Mrps10%3D Occurrence Handle2818292
A Carr K Samaras S Burton et al. (1998) ArticleTitleA syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 12 F51 Occurrence Handle1:STN:280:DyaK1c3otFSqtQ%3D%3D Occurrence Handle9619798
RW Chan IR Titze (1998) ArticleTitleViscosities of implantable biomaterials in vocal cord augmentation surgery. Laryngoscope 108 725 Occurrence Handle10.1097/00005537-199805000-00019 Occurrence Handle1:STN:280:DyaK1c3lt1ahug%3D%3D Occurrence Handle9591554
AL Chen P Desai EM Adler PE Di Cesare (2002) ArticleTitleGranulomatous inflammation after hylan g-f 20 viscosupplementation of the knee: a report of six cases. J Bone Joint Surg (Am) 84-A 1142
N-X Cheng Y-L Wang J-H Wang X-M Zhang H Zhong (2002) ArticleTitleComplications of breast augmantation with injected hydrophilic polyacrylamide gel. Aesth Plast Surg 26 375 Occurrence Handle10.1007/s00266-002-2052-4
Cohen SR, Holmes RE (2004) Artecoll: A longlasting wrinkle augmentation material. To be published in Plast Reconstr Surg 113:
HP Drosbeck SS Rothstein KI Gumaer AD Sherer RG Slighter (1984) J Oral Maxillofac Surg 42 143 Occurrence Handle6321707
DM Duffy (1998) Injectable liquid silicone: new perspectives. AW Klein (Eds) Tissue Augmentation in Clinical Practice: Procedures and Techniques. Marcel Dekker New York 237–267
DM Duffy (2002) ArticleTitleThe silicone conundrum: A battle of anecdotes. Dermatol Surg 28 590 Occurrence Handle10.1046/j.1524-4725.2002.22081_1.x Occurrence Handle12135512
F Duranti G Salti B Bovani M Calandra M Rosati (1998) ArticleTitleInjectable hyaluronic acid gel for soft tissue augmentation. Dermatol Surg 24 1317 Occurrence Handle10.1016/S1076-0512(98)00151-4 Occurrence Handle9865196
BL Eppley D-J Summerlin CD Prevel AM Sadove (1994) ArticleTitleEffects of positively charged biomaterial for dermal and subcutaneous augmentation. Aesth Plast Surg 18 13
RA Ersek AA Beisang (1991) ArticleTitleBioplastique. A new textured copolymer microparticle promises permanence of soft-tissue augmentation. Plast Reconstr Surg 87 693
C Feretis P Benakis C Dimopoulos et al. (2001) ArticleTitleEndoscopic implantation of Plexiglas (PMMA) microspheres for the treatment of GERD. Gastrointest Endosc 53 423 Occurrence Handle10.1067/mge.2001.113912 Occurrence Handle1:STN:280:DC%2BD3M7oslSjtA%3D%3D Occurrence Handle11275880
AV Filatov SN Mirolyubov (1998) ArticleTitleContour plasty of maxillofacial soft tissues with biocompatible polyacrylamide gel (Russian). Stomatologiia (Mosk) 77 45 Occurrence Handle1:STN:280:DyaK1c7nt1Citg%3D%3D
PW Flint RL Corio CW Cummings (1997) ArticleTitleComparison of soft tissue response in rabbits following laryngeal implantation with hydroxylapatite, silicone rubber and Teflon. Ann Oto Rhino Laryngol 106 399 Occurrence Handle1:STN:280:ByiB1MjmtlI%3D
PM Friedman EA Mafong AN Kauvar RG Geronemus (2002) ArticleTitleSafety data of injectable nonanimal stabilized hyaluronic acid gel for soft tissue augmentation. Dermatol Surg 28 491 Occurrence Handle10.1046/j.1524-4725.2002.01251.x Occurrence Handle12081677
MI Garcia-Domingo J Alijotas-Reig A Cistero-Bahima F Tresserra E Enrique (2000) ArticleTitleDisseminated and recurrent sarcoid-like granulomatous panniculitis due to bovine collagen injection. J Invest Allergol Clin Immunol 10 107
D Geile I Zinner F Erbel M Schaefer G Osterholzer (2001) Diagnosis and non-surgical treatment of faecal incontinence in the proctological practice. P Fruehmorgen H-P Bruch (Eds) Non-Neoplastic Diseases of the Anorectum. Kluwer Academic Publishers Dordrecht
L Hallen C Johansson C Laurent (1999) ArticleTitleCross-linked hyaluronan (Hylan B gel): an injectable remedy for treatment of vocal fold insufficiency—an animal study. Acta Otolaryngol (Stockholm) 119 107 Occurrence Handle1:CAS:528:DC%2BD3MXitlCgu7k%3D
CW Hanke (1998) Adverse reactions to bovine collagen. AW Klein (Eds) Tissue Augmentation in Clinical Practice. Procedures and Techniques. Marcel Dekker New York 145–154
EL Kazachkov AB Fridman SA Friss (1998) ArticleTitleGranulomatous pleurisy after mammoplasty induced by polyacrylamide gel. (Russian). Arkh Patol 60 58 Occurrence Handle1:STN:280:DyaK1czmslKrsQ%3D%3D
BM Kinney CE Hughes III (2001) ArticleTitleSoft tissue fillers: An overview. Aesth Surg J 21 469 Occurrence Handle10.1067/maj.2001.119300
AW Klein ML Elson (2000) ArticleTitleThe history of substances for soft tissue augmentation. Dermatol Surg 26 1096 Occurrence Handle1:STN:280:DC%2BD3M%2FovVeltg%3D%3D Occurrence Handle11134984
FS Kolle (1911) Plastic and Cosmetic Surgery. D Appleton New York 209–230
G Lemperle H Hoehler (1975) Granulome nach Unterspritzung von Gesichtsfalten mit Teflon-Paste. H Hoehler (Eds) Plastische und Wiederherstellungschirurgie Schattauer Stuttgart 335–340
G Lemperle N Gauthier-Hazan M Lemperle (1998) ArticleTitlePMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: Refinements and statistical results. Aesth Plast Surg 22 365 Occurrence Handle10.1007/s002669900217
G Lemperle (2000) ArticleTitleHyaluronsäure zur Faltenunterspritzung. Arzneimittel-, Therapie-Kritik 3 635
G Lemperle JJ Romano M Busso (2003) ArticleTitleSoft tissue augmentation with Artecoll: 10-year history, indications, technique and complications. Dermatol Surg 29 573 Occurrence Handle10.1046/j.1524-4725.2003.29140.x Occurrence Handle12786699
Lemperle G, Legaz ME (2004) Biocompatibility of injectable microparticles. Aesth Plast Surg, submitted
NJ Lowe CA Maxwell P Lowe MG Duick K Shah (2001) ArticleTitleHyaluronic acid skin fillers: Adverse reactions and skin testing. J Am Acad Dermatol 45 930 Occurrence Handle10.1067/mjd.2001.117381 Occurrence Handle1:STN:280:DC%2BD3MnmsFOqtQ%3D%3D Occurrence Handle11712042
JR Lupton TS Alster (2000) ArticleTitleCutaneous hypersensitivity reaction to injectable hyaluronic acid gel. Dermatol Surg 26 135 Occurrence Handle10.1046/j.1524-4725.2000.99202.x Occurrence Handle1:STN:280:DC%2BD3cvgtFyjtA%3D%3D Occurrence Handle10691942
F Manna M Dentini P Desideri O De Pita E Mortilla B Mars (1999) ArticleTitleComparative chemical evaluation of two commercially available derivatives of hyaluronic acid (Hylaform from rooster combs and Restylane from streptococcus) used for soft tissue augmentation. J Eur Acad Dermatol Venerol 13 183 Occurrence Handle10.1016/S0926-9959(99)00089-6 Occurrence Handle1:STN:280:DC%2BD3c7gsFSnsg%3D%3D
F Mazzoleni C Dominici T Lotti et al. (2000) ArticleTitleFormacryl: Un nuovo biopolimero al servizio della medicina “piu un endoprotesi che un filler.” Dermatologia 1 13
DJ Misiek JN Kent RF Carr (1984) ArticleTitleSoft tissue responses to hydroxylapatite particles of different shapes. J Oral Maxillofac Surg 42 150 Occurrence Handle1:STN:280:BiuC3sfgvVw%3D Occurrence Handle6321708
RR Moscona R Bergman R Friedman-Birnbaum (1993) ArticleTitleAn unusual late reaction to Zyderm I injections: a challenge for treatment. Plast Reconstr Surg 92 331
VB Morhenn G Lemperle RL Gallo (2002) ArticleTitlePhagocytosis of different particulate dermal filler substances by human macrophages and skin cells. Dermatol Surg 28 484 Occurrence Handle10.1046/j.1524-4725.2002.01273.x Occurrence Handle12081676
C Naoum D Dasou-Plakida (200) ArticleTitleDermal filler materials and botulin toxin. Int J Dermatol 40 606
RS Narins F Brandt J Leyden ZP Lorenc M Rubin S Smith (2003) ArticleTitleA randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg 29 588 Occurrence Handle10.1046/j.1524-4725.2003.29150.x Occurrence Handle12786700
MS Neto S Passy (1999) Rellenamiento cutaneo y correccion de las deformidades del rostro con el uso de microesferas de PMMA—un nuevo enfoque. . . (Eds) Proceedings of the 28th Argentinian Congress of Plastic Surgery . Cordoba 1–8
KW O’Connor GA Lehman (1988) ArticleTitleEndoscopic placement of collagen at the lower esophageal sphincter to inhibit gastroesophageal reflux: a pilot study of 10 medically intractable patients. Gastrointest Endoscop 34 106 Occurrence Handle1:STN:280:BieB3M3gs1Y%3D
M Olenius (1998) ArticleTitleThe first clinical study using a new biodegradable implant for the treatment of lips, wrinkles and folds. Aesth Plast Surg 22 97 Occurrence Handle10.1007/s002669900172
J Pannek FH Brands J Schewe T Senge (2001) ArticleTitleParticle migration following transurethral injection of carbon coated beads for stress urinary incontinence. J Urol 165 IssueIDSuppl 5 74
S Pollack (1999) ArticleTitleSome new injectable dermal filler materials: Hylaform, Restylane, and Artecoll. J Cutan Med Surg 3 IssueIDSuppl 4 S4–S29
MJ Rapaport C Vinnik H Zarem (1996) ArticleTitleInjectable silicone: cause of facial nodules, cellulites, ulceration, and migration. Aesth Plast Surg 20 267 Occurrence Handle10.1007/s002669900032 Occurrence Handle1:STN:280:BymA38vitVU%3D
C Requena MJ Izquierdo M Navarro et al. (2000) ArticleTitleAdverse reactions to injectable aesthetic microimplants. Am J Dermatopathol 23 197 Occurrence Handle10.1097/00000372-200106000-00006
CM Rudolph HP Soyer S Schuller-Petrovic H Kerl (1999) ArticleTitleForeign body granulomas due to injectable aesthetic microimplants. Am J Surg Pathol 23 113 Occurrence Handle10.1097/00000478-199901000-00013 Occurrence Handle1:STN:280:DyaK1M7gtlOrtA%3D%3D Occurrence Handle9888711
JP Rubin MJ Yaremchuk (1997) ArticleTitleComplications and toxicities of implantable biomaterials used in facial reconstructive and aesthetic surgery: A comprehensive review of the literature. Plast Reconstr Surg 100 1
T Saint-Marc M Partisani I Poizot-Martin et al. (1999) ArticleTitleA syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 13 1659 Occurrence Handle1:STN:280:DyaK1MvjslaltA%3D%3D Occurrence Handle10509567
P Senet H Bachelez L Ollivaud D Vignon-Pennamen L Dubertret (1999) ArticleTitleMinocycline for the treatment of cutaneous silicone granulomas. Br J Dermatol 140 985 Occurrence Handle10.1046/j.1365-2133.1999.02853.x Occurrence Handle1:STN:280:DyaK1M3ot1amsw%3D%3D Occurrence Handle10354059
R Shafir A Amir E Gur (2000) ArticleTitleLong-term complications of facial injections with Restylane (injectable hyaluronic acid). Plast Reconstr Surg 106 1215
G Spenlehauer M Vert JP Benoit A Boddaert (1989) ArticleTitleIn vitro and in vivo degradation of poly(D,L-lactide/glycolide) type microspheres made by solvent evaporation method. Biomaterials 10 557 Occurrence Handle10.1016/0142-9612(89)90063-X Occurrence Handle1:CAS:528:DyaK3cXisFCqtQ%3D%3D Occurrence Handle2605288
VJ Tomacic-Jeciz K Merritt TH Umbreit (2001) ArticleTitleSignificance of type and the size of biomaterial particles on phagocytosis and tissue distribution. J Biomed Mater Res 55 523 Occurrence Handle10.1002/1097-4636(20010615)55:4<523::AID-JBM1045>3.0.CO;2-G Occurrence Handle11288080
E-D Voy J Mohasseb (2002) ArticleTitleLipoatrophie als seltene Komplikation nach Auffüllung der Nasolabialfalten mit injizierbaren Implantaten. Magazin Aesth Chir 2 .
WE Whitehead A Wald NJ Norton (2001) ArticleTitleTreatment options for fecal incontinence. Dis Colon Rectum 44 131 Occurrence Handle1:STN:280:DC%2BD38%2FosVyquw%3D%3D Occurrence Handle11805574
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lemperle, G., Morhenn, V. & Charrier, U. Human Histology and Persistence of Various Injectable Filler Substances for Soft Tissue Augmentation. Aesth. Plast. Surg. 27, 354–366 (2003). https://doi.org/10.1007/s00266-003-3022-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00266-003-3022-1