Brief communication about injectable fillers in aesthetic medicine (Part 2)

Brief communication about injectable fillers in aesthetic medicine (Part 2)



Dr Sky Wong 

Carboxymethylcellulose (CMC)

It is a non-cross-linked cellulose derivative that forms bioabsorbable gel with water to give immediate filling effect and structural support to tissues. It is not usually given alone but as a suspension and texture modifier mixed with other filler materials, commonly Calcium Hydroxylapatite (CaHA) and Polycaprolactone (PCL). It provides immediate volume effect and allows these primary materials enough time to exert their biostimulatory effect to produce collagen which fills up the site of interest before the CMC degrades and was resorbed. The rate of resorption of CMC depends on the molecular sizes[1] but there is no clinical data available during the literature search.

Autologous fat

Autologous fat is a long history filler since century ago. Despite perfectly compatible, adipocyte survival rate which directly affects the outcome and longevity is the chief concern. The uptake rate can be anywhere from 20 to 90%[2]. Therefore, subject selection, technique of harvesting, processing and transfer injection are very important. For underweight patient, poor quality and amount of fat may be yielded, therefore some nourishing diet may be required before the procedure is done. During harvesting, low heat, low trauma at favorable quality site are required to ensure good quality adipocyte are collected without damaging them. Adipose-derived stem cells (ASC) is shown to have improved the uptake and can be prepared by special techniques through isolating the stromal vascular fraction (SVF) which gives better neovascularization for fat survival[3].

	Hyaluronic acid (HA)	Calcium Hydroxylapatite (CaHA)	Poly Lactic Acid (PLA)	Polycaprolactone (PCL)	Carboxymethylcellulose (CMC)	Autologus fat injection
Property	Organic, Linear polysaccharide, a family of GAGs, naturally found in human skin	Inorganic, Naturally found in human teeth and bone	Organic, polymer form of lactic acid	Organic, aliphatic polyester	Organic, non-cross-linked cellulose derivative	Organic, own tissue
Manufacturing and processing	Bacterial bioengineering	inorganic bioceramic synthesize	Can be derived from starch	Ring opening polymerization	Etherification of cellulose	Liposuction, filtering, centrifugation, ASC enhancement
Biodegradable	Yes	Yes	Yes	Yes	Yes	Yes
Metabolism	Hydrolysis, enhanced by hyaluronidase	Biodegraded to Calcium and Phosphate, removed by phagocytosis	Biodegraded to carbon dioxide and water	Biodegraded to carbon dioxide and water	Biodegraded to carbon dioxide and water	As normal fat
Longevity	Variable dependent on molecular size and cross-linking, from weeks to 2 years	12-18 months for CaHA, variable for the induced collagen and elastin	Up to 3 years for PLA, variable for the induced collagen	From 1 – 4 years dependent on the length of the polymer, variable for the induced collagen	No clinical data for injectables	20-90% survival rate up to 3-6 years
Preferred layer of injection	From intradermal to subcutaneous and periosteum	Mostly preferable to subcutaneous to periosteum	Mostly preferable to subcutaneous to periosteum	Mostly preferable to subcutaneous to periosteum	Subcutaneous to periosteum together with the primary filler	Subcutaneous and deep fasciae

Table 1: comparisons of different aspects of commonly used fillers

Filler safety and complications

Filler Quality

Fillers are regarded as medical devices. There is so far no compulsory regulation nor legislation in mandating product registration yet, all are in voluntary basis. However, choosing registered one guarantees better quality and safety profiles, because it usually requires efficacy and safety certificates and profiles which are endorsed by Conformité Européenne (CE) or Food and Drug Administration (FDA).  

Complications

Since the structure of skin, body compartments and vital structures including nerve and vessels are complicated, therefore well-trained health care doctor are required to perform the procedure accurately. There are many complications from simple (e.g bruising and minor bleeding) to severe (e.g. vascular insultation, nerve injury, granuloma formation and infection)[4]. Therefore, comprehensive training in theory, skills and management of complications are very important.

Vascular embolism

Only small amount of filler can give rise to arterial embolism to result in disastrous consequences like blindness as little as 0.085ml[5]. Periorbital area is notorious for causing blindness due to vascular insultation, however other injection sites also can give rise to such severe complication due to extensive arcades and anastomosis of the facial arteries including chin and nasolabial fold. Other embolic consequences include skin/soft tissue necrosis and stroke[6]. Low pressure, retrograde and cannula injection showed improved safety but not absolute. If unwanted situation occurred, hyaluronidase, aggressive massage, warm compresses, topical nitroglycerin, enoxaparin, aspirin, dexamethasone and antibiotics are advocated for the acute management of vascular insultation[7]. Hyperbaric oxygen therapy was also documented to be helpful[8].

Figure 1: White arrows shows obstructed retinal artery with white infiltrations with retinal oedema, courtesy of Kim et al[9].

Biofilm

Biofilm is one of the important (although rare) but under-diagnosed condition in filler injection. This occur more commonly with longer duration fillers. Onset is from a few days to months. They are sometimes misdiagnosed as “hypersensitive reaction” or missed due to subtle presentation and negative culture results[10]. It has extensive extracellular matrix that devoid of the body immune attack and antibiotics effect, it forms a self-sustaining “ecosystem” that can last for an extremely long period of time. Management of such condition includes a high index of suspicion, give hyaluronidase if for HA[11] and long-term high-dose broad-spectrum antibiotics. Surgical removal or expressing away of the filler may be required if the above fails. Prevention is better than cure, meticulous aseptic technique is much required.

Techniques and reversal intervention

Improper reconstitution, uneven product distribution in the suspension, improper injection techniques and wrong layer of injection all contribute to undesirable treatment outcomes, nodule formation, and other complications. Amount all fillers, only HA has courter acting dissolution agent: hyaluronidase. The others are non-dissolvable and must wait for natural biodegradation or need surgical correction once the unpleasant filling effect or nodule is established. Early intralesional administration of normal saline or corticosteroid can be helpful[12], but injection site unevenness or atrophy may result. Dense fibrous nodule is also technically difficult to target and inject at accurately.

Conclusion

Fillers are useful substances for reconditioning, restoring and recontouring of skin and body parts. It not only improves one’s appearance but also salvages them psychologically, be it by improving self-confidence or by avoidance of stigmatization. There are a wide range of filler selections existing in the market with different properties. Adequate indication and combination of filler use give the best treatment outcome. Training for knowledge and techniques are very much required to prevent both trivial and disastrous morbidity and perhaps mortality.

Dr Sky Wong 

Hong Kong 

Reference:

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[1] Siritientong, Tippawan, and Pornanong Aramwit. "Characteristics of carboxymethyl cellulose/sericin hydrogels and the influence of molecular weight of carboxymethyl cellulose." Macromolecular Research 23.9 (2015): 861-866.

[2] Toyserkani, Navid Mohamadpour, Marlene Louise Quaade, and Jens Ahm Sørensen. "Cell-assisted lipotransfer: a systematic review of its efficacy." Aesthetic plastic surgery 40.2 (2016): 309-318.

[3] Yoshimura, Kotaro, et al. "Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells." Aesthetic plastic surgery 32.1 (2008): 48-55.

[4] Goisis, Mario, ed. Injections in Aesthetic Medicine: Atlas of Full-face and Full-body Treatment. Springer Science & Business Media, 2013.

[5] Khan, Tanya T., et al. "An anatomical analysis of the supratrochlear artery: considerations in facial filler injections and preventing vision loss." Aesthetic surgery journal 37.2 (2017): 203-208.

[6] Egido, J. A., et al. "Middle cerebral artery embolism and unilateral visual loss after autologous fat injection into the glabellar area." Stroke 24.4 (1993): 615-616.

[7] Haneke, E. (2015). "Managing complications of fillers: rare and not-so-rare." Journal of Cutaneous and Aesthetic Surgery 8(4): 198.

[8] Henderson, Raven, Debra A. Reilly, and Jeffrey S. Cooper. "Hyperbaric Oxygen for Ischemia due to Injection of Cosmetic Fillers: Case Report and Issues." Plastic and Reconstructive Surgery Global Open 6.1 (2018).

[9] Kim YK, Jung C, Woo SJ, Park KH. Cerebral Angiographic Findings of Cosmetic Facial Filler-related Ophthalmic and Retinal Artery Occlusion. J Korean Med Sci. 2015;30(12):1847-55.

[10] Dayan, Steven H., John P. Arkins, and Renata Brindise. "Soft tissue fillers and biofilms." Facial Plastic Surgery 27.01 (2011): 023-028.

[11] Pecharki, D., F. C. Petersen, and A. Aa Scheie. "Role of hyaluronidase in Streptococcus intermedius biofilm." Microbiology 154.3 (2008): 932-938.

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