Brief communication about injectable fillers in aesthetic medicine (Part 1)

Brief communication about injectable fillers in aesthetic medicine (Part 1) 

Dr Sky Wong 

Introduction

Injectable filler by definition is a biocompatible material to be injected to the cutaneous, subcutaneous, and periosteal layers for re-volumization of the respective areas. In fact, with different properties of the fillers and injection techniques, the treatment can result in reconditioning, restoring or recontouring of the corresponding skin area and body part. It was first to be used in lipodystrophy patient to improve the appearance and avoid stigmatization[1]. The result was highly satisfied by the patients[2], therefore it is further wide-spreadly adopted in aesthetic field at fast paces. The applications can be from face to body parts like gluteal areas, from skin to deep seated periosteal layers. The properties of a good soft tissue filler are biocompatible, non-allergic inducing, integrative to soft tissues, good in plasticity and elasticity, of adequate G-prime value, long lasting, low-cost, non-migratory and easy to administer. However, there exists none for such ideal filler, so a combination of fillers in a coherent approach with good knowledge of the fillers properties is the utmost important to achieve an optimal effect in a safe way.

Filler choices and properties

There are numerous soft-tissue fillers across the world. The commonly used ones which are discussed in this article include Hyaluronic acid (HA), Calcium Hydroxylapatite (CaHA), Poly Lactic Acid (PLA), Polycaprolactone (PCL), Carboxymethylcellulose (CMC), and Autologous fat.

Hyaluronic acid (HA)

HA is a temporary filler under the family of the glycosaminoglycans (GAGs) which is found abundant in our skin as extracellular matrix of various molecular sizes. It is negatively charged and binds water molecules. It provides numerous biological functions e.g. structural support, nutrient diffusion, cell migration and proliferation etc. It is metabolized by hydrolysis facilitated with hyaluronidase. In pharmaceutical manufacturing of HA, it is by biochemical engineering using bacterial fermentation such as Streptococcus equi[3]. Low molecular size and non-cross-linked HA provides hydration and rejuvenation function, while large molecular size and cross-linked HA gives more structural support and lasts longer to exert re-volumization and recontouring functions. They follow the rule of isovolumetric degradation in which HA molecules break down and are then replaced by water molecules, theoretically it can maintain its volume with time but results in less dense and less viscous texture gradually. Although a number of HAs are approved by the FDA for wrinkles such as nasolabial fold and face contour deficiencies, there are a lot of "off-label" uses like tear trough treatment, apple zone and temporal zone revolumization etc.  

Calcium Hydroxylapatite (CaHA)

CaHA is a non-pyrogenic biocompatible inorganic bioceramic which is synthesized through chemical deposition, biomimetic deposition, sol-gel route (wet-chemical precipitation) or electrodeposition[4]. It is usually presented as semi-solid state in the form of 25-45μm microspheres in a suspension of gel carrier with carboxymethylcellulose (CMC) which gives immediate structural support. It is biodegradable in the same metabolic pathway as our bone does and removed by phagocytosis. Apart from being a filler and biostimulator, CaHA provides support and scaffold lattice that guides fibroblast ingrowth for neocollagenesis/neoelastinogenesis and promote surrounding soft tissue formation. Study also demonstrated conversion of type III collagen to type I as well at 4th month and onwards[5]. It can provide different functional properties, G-primes and viscosities by various degree of hyperdilutions, therefore it can be used in different areas and indications from filler effect (i.e. tissue augmentation and re-volumization) to biostimulator effect (i.e. collagen induction and rejuvenation)[6]^,[7]. (It is in a suspension of CMC to provide immediate volume effect.) The longevity of CaHA is generally 12-18 months[8]. It is approved by FDA for moderate to severe wrinkles and folds (nasolabial folds), facial augmentation and hand rejuvenation. 

Figure 1: The relatively uniform sized CaHA spheres, Courtesy of Holzapfel et al[9]

Poly Lactic Acid (PLA)

This is a polymer of lactic acid from alpha-hydroxy-acid family which can be derived from starch and is commercially prepared in L-enantiomer form (the Poly L-Lactic Acid, PLLA) or racemic form. It is biocompatible, biodegradable and can be fully metabolized to carbon dioxide and water. The PLA microparticles (some pharmaceutical preparations are at the sizes from 40 to 63 μm) initiate neocollagenesis as a result of activation of fibroblasts[10]. It is reconstituted in sterile water with lignocaine and then injected to the skin and soft tissue. It is advised to reconstitute at least 24 hours (best 72 hours) before use[11], although the protocol differs in different preparations. Post-injection massage was controversial or claimed to be possibly skipped in some commercial preparations, but most studies tended to show massage reduced complication of nodule formation and in general one should follow the rule of 5 (post-injection for 5 days, 5 times a day, 5 minutes each time)[12]. The life span is up to 25 months[13] to 3 years[14]. It has been approved by FDA for restoration and correction of the signs of facial fat loss, nasolabial folds and other facial wrinkles.

Polycaprolactone (PCL)

PCL is an organic aliphatic polyester belonging to the poly-α-hydroxy acid group. It is bioabsorbable and hydrolytically degradable into carbon dioxide and water[15].  Investigations also showed it is non-cytotoxic, non-pyrogenic and biocompatible. Its biostimulator effect induces collagen formation which results in filling effect. Similar to CaHA, it also provides a scaffold for collagen infiltration which facilitates soft tissue building and is prepared in a suspension of CMC to give adequate texture and immediate effect after injection. The PCLs are made to microspheres at 25-50 µm sizes in some pharmaceutical preparations. The longevity of PCL depends on the extensiveness of the polymer chain, officially from 1 – 4 years. Before injection, PCL can be mixed with lignocaine for the comfort of patient during injection. Its parental PCL medical devices (like suture materials) are FDA approved, but not the injectable PCL itself at present moment. Actually, there are studies including randomized controlled trials demonstrate its efficacy and safety[16].  

(to be continued)

Dr Sky Wong 

Hong Kong 

Reference:

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[1] Gooderham, Melinda, and Nowell Solish. "Use of hyaluronic acid for soft tissue augmentation of HIV‐associated facial lipodystrophy." Dermatologic surgery 31.1 (2005): 104-108.

[2] Sturm, Lana P., et al. "A systematic review of permanent and semipermanent dermal fillers for HIV-associated facial lipoatrophy." AIDS patient care and STDs 23.9 (2009): 699-714.

[3] Chong, Barrie Fong, et al. "Microbial hyaluronic acid production." Applied microbiology and biotechnology 66.4 (2005): 341-351.

[4] Ferraz M, Monteiro F, Manuel C. Hydroxyapatite nanoparticles: a review of preparation methodologies. Journal of Applied Biomaterials and Biomechanics. 2004;2(2):74-80.

[5] Yutskovskaya YA, Kogan EA. Improved Neocollagenesis and Skin Mechanical Properties After Injection of Diluted Calcium Hydroxylapatite in the Neck and Décolletage: A Pilot Study. Journal of drugs in dermatology: JDD. 2017;16(1):68-74.

[6] Hevia, Oscar. "A retrospective review of calcium hydroxylapatite for correction of volume loss in the infraorbital region." Dermatologic Surgery 35.10 (2009): 1487-1494.

[7] Range, Product, Image Skin Care, and Beauty Tips. "The CO2 laser is the most resourceful laser in the management of cutaneous lesions. It is the gold standard amongst all ablative lasers. Potential applications of this laser in day to day dermatological practice are boundless."

[8] Tzikas, Thomas L. "Evaluation of the Radiance FN soft tissue filler for facial soft tissue augmentation." Archives of facial plastic surgery 6.4 (2004): 234-239.

[9] Holzapfel AM, Mangat DS, Barron DS. Soft-tissue augmentation with calcium hydroxylapatite: histological analysis. Archives of facial plastic surgery. 2008;10(5):335-8.

[10] Simamora, Pahala, and Wendy Chern. "Poly-L-lactic acid: an overview." Journal of drugs in dermatology: JDD 5.5 (2006): 436-440.

[11] Narins, Rhoda S. "Minimizing adverse events associated with poly‐L‐lactic acid injection." Dermatologic Surgery 34 (2008): S100-S104.

[12] Palm, Melanie D., et al. "Cosmetic use of poly‐l‐lactic acid: a retrospective study of 130 patients." Dermatologic Surgery 36.2 (2010): 161-170.

[13] Narins, Rhoda S., et al. "A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles." Journal of the American Academy of Dermatology 62.3 (2010): 448-462.

[14] Salles, A. G., et al. "Evaluation of the poly-L-lactic acid implant for treatment of the nasolabial fold: 3-year follow-up evaluation." Aesthetic plastic surgery 32.5 (2008): 753-756.

[15] Heimowska, Aleksandra, Magda Morawska, and Anita Bocho-Janiszewska. "Biodegradation of poly (ε-caprolactone) in natural water environments." Polish Journal of Chemical Technology 19.1 (2017): 120-126.

[16] Moers‐Carpi, Marion Michaela, and Sally Sherwood. "Polycaprolactone for the correction of nasolabial folds: A 24‐month, prospective, randomized, controlled clinical trial." Dermatologic Surgery 39.3pt1 (2013): 457-463.