Implants: synthetic fillers

Although most injectable and implantable materials used for soft tissue augmentation are of biological origin, a number of synthetic materials have also been used for this purpose, with varying degrees of success.

Some of the recently developed materials show promise in terms of their permanence and stability.

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Liquid silicone

Silicone is a polymer of dimethylsiloxanes. Liquid silicone is a clear, colorless, and relatively inert liquid. As an injection material, it was first used in Asia, Europe, and Latin America before coming to the United States. In 1963, Dow Corning (USA) created liquid medical silicone 360, and later a purer form of silicone, MDX 4-4011.

The technique of silicone injection is probably the most critical point for a successful treatment. It must be injected into the dermis and fat in minute quantities. Each particle is enclosed in a fibrous capsule over the following weeks. The tissue enlargement and filling are the result of a fibroblastic reaction, not just the presence of silicone. The fibrosing reaction and capsule formation occur over several weeks. Since silicone implantation results in a permanent result, extreme caution is necessary and deliberate undercorrection is strongly recommended.

Silicone implants are associated with the serious complications already described, including inflammation, induration, discoloration, ulceration, displacement, and formation of silicone granulomas. It should be noted that many of the complications described are the result of using silicone implants of unknown purity or even adulterated silicone containing olive oil or other components, rather than purified Dow Corning silicone (MDX 4-4011). Liquid silicone received FDA approval for ophthalmic and orthopedic use in 1994. However, injectable silicone has not yet received approval for tissue augmentation and remains dangerous due to the irreversibility of the procedure.

Polymethyl methacrylate (Artecoll)

Polymethyl methacrylate (PMMA) microspheres (Artecoll, manufactured by Rofil Medical International, the Netherlands) are used in Europe as an injectable filler. The microspheres are 20-40 µm in size - large enough to avoid phagocytosis, but small enough to be used intradermally. PMMA is supplied in a 3.5% collagen solution containing 0.3% lidocaine. The microspheres have a smooth surface and are covered with a layer of monocytes in the first 2 days, a layer of fibroblasts after 2 months and a fibrous capsule after 7 months. The main indication for the use of Artecoll are naturally occurring folds and wrinkles on the face. Usually, 1 ml of the product is enough to correct folds in the glabella area, nasolabial folds, sagging corners of the mouth and to enlarge the lips. Artecoll is not suitable for the correction of crow's feet, because they are too superficial.

Common reactions to Artecoll injections include swelling, erythema, mild pain, and itching that last for several days. Other, serious complications are rare. However, because the effect is irreversible, patients who experience displacement, inflammatory reaction, or infection cannot be offered any alternative treatment other than wide tissue excision. Cosmetically, this makes the material less attractive and even dangerous. Experience with its use is limited and long-term results are unknown. Artecoll is not approved for use by the Food and Drug Administration.

Bioplastics

Bioplastique (manufacturer Uroplasty, Netherlands) is a white, highly textured, two-phase polymer with a solid phase containing microparticles of textured vulcanized silicone rubber and a liquid phase containing a biocompatible plasdone hydrogel. It is an inert injection material with the limitations of injectable silicone. Since the microparticles have a diameter of 100-400 μm, they are not captured by macrophages, since phagocytosis is limited to particles smaller than 60 μm. Due to the large particle size, Bioplastique cannot be injected into superficial tissues, but it is ideal for subcutaneous placement. The drug can be used to correct retracted scars, sunken cheeks, nasal bridge deformities, subcutaneous contour defects and for lip augmentation. Bioplastique is too voluminous to correct folds, wrinkles and superficial meshes. Since the fibroblast reaction and collagen deposition continue for several weeks, provide additional volume increase and lifelong results, deliberately insufficient correction of cicatricial defects is recommended. Hypercorrection can lead to contour disturbances.

Several studies have shown a giant cell reaction to Bioplastique as a foreign body. Histological analysis showed an acute moderate inflammatory reaction, which becomes chronic as the gel carrier is absorbed. The hydrogel is replaced by fibrin and then by fibroblasts. After 7 days, the macrophages fuse into giant cells, as they are unable to phagocytose these particles. The giant cells remain in a stable form on the surface of the particles.

Complications occur if the material is injected superficially into the skin, or if too much material is injected, creating a dense, palpable mass. In such cases, the implant and surrounding tissue can be removed by microliposuction or surgical excision. Concerns about irreversibility and the potential for a chronic inflammatory response limit the use of this product. It is not available in the United States and is not approved for use by the Food and Drug Administration.

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PPTFE (porous polytetrafluoroethylene)

Porous polytetrafluoroethylene (Ultrasoft, manufactured by Tissue Technologies Inc., USA; Gore-Tex, manufactured by WL Gore, USA) is an extremely biocompatible, inert carbon-based alloplast that has been used for the production of reliable and effective vascular prostheses for over 20 years. Since its introduction as a vascular material in the 1970s, the field of application of ePTFE has expanded to include hernia repair and reconstructive cosmetic surgeries. The advantages of this prosthetic material are well established and documented. ePTFE has a multiaxial microstructure consisting of nodules interconnected by fine fibrils and is produced in various "pore sizes". It is easy to handle, causes minimal tissue reaction and is non-thrombogenic. After implantation, the material retains its strength, thickness, size and flexibility. Its microfibrillar structure allows minor cell penetration and connective tissue ingrowth. Comparative studies of different forms of ePTFE have shown the superiority of the tubular form (Soft-Form) in terms of stability and tissue ingrowth. Longitudinal tissue ingrowth and the lumen of the implant fix it better and minimize the risk of migration. Meanwhile, the relatively small migration of fibroblasts into the walls of the implant makes it easy to remove.

SoftForm is available in a kit, including the implant material and a cutting trocar placed in an external cannula. The implants are 5, 7 and 9 cm in length and 2.4, 3.2 and 4 mm in diameter. They are used to correct nasolabial folds and the perioral area, facial scars, soft tissue defects and for lip augmentation. The procedure is performed in the doctor's office under local anesthesia, after careful marking of the soft tissue defect, fold or wrinkle with the patient in an upright position. To achieve the desired correction, precise tunneling of the subcutaneous tissue under the defect with a trocar catheter is necessary.

There are two unacceptable long-term complications with Softform. It has been observed that the material becomes denser (more palpable) a few weeks after implantation. This is assumed to be due to the material growing into the walls - for example, into the walls of the tube. In addition, many patients experience a shortening of the material in the longitudinal direction, especially in the lips. This is a consequence of the "accordion" effect in the thick walls of the tubes. Ultrasoft for lip implantation is made with thinner walls (softer before and after implantation) and is longer. Early results show that the characteristics of this implant are significantly improved compared to Softform.

For correction of the nasolabial fold, small punctures are made in the fold, approximately at the level of the oral commissure, and in the groove at the ala of the nose. Tunneling of the subcutaneous tissue is performed with the tip of the trocar. Excessive resistance to its advancement indicates an incorrect depth, in which case the trocar should be removed and moved, as a rule, a little deeper. When the implant is visible in both the entry and exit punctures, the cannula and trocar are removed. The skin over the implant is massaged to evenly distribute the material, and its excess is cut off. Both lumens of the implant are left open (to allow ingrowth of connective tissue), immersed in the wound, and the incisions are sutured with non-absorbable monofilament sutures. Antibiotics are prescribed locally and orally for several days. In most cases, the entry and exit punctures become invisible after a short healing period, but if the punctures are not sutured very precisely, light polishing may be required.

Lip augmentation follows the same principles as nasolabial fold correction. For the upper lip, better results are achieved by augmenting the vermilion border with two implant segments, while preserving the Cupid's bow. The implant is placed just below the vermilion border of the upper lip. A third implant placed 3 months after the initial vermilion correction may produce an "inversion effect," increasing the augmentation. This "triangular" technique increases the vertical height of the lip. The lower lip is usually augmented with one long (9 cm) implant covering the entire lip, placed just below the vermilion border. Complications, including displacement, are rare and are generally related to technique defects. Short-term swelling and redness over the implantation site are to be expected. Ultrasoft is FDA-cleared and available in the United States.

Botulinum exotoxin

The use of botulinum exotoxin in cosmetic surgery has become widespread recently. Its introduction into cosmetology is based on the fact that facial folds are significantly reduced in patients treated with botulinum exotoxin A (BTX-A) for idiopathic blepharospasm. The effect of BTX-A on folds and lines is due to the fact that many of them are formed as a result of contraction of the underlying muscles. By weakening or paralyzing the corresponding muscle, BTX-A can lead to smoothing of the face.

Several properties of BTX-A make it attractive for the correction of facial folds, as an alternative to surgery and filler techniques. BTX-A is safer, more locally effective, and easier to apply. In addition, the toxin acts selectively and reversibly; therefore, it has relatively few side effects.

Botulinum neurotoxin (BTX) is produced by the anaerobic bacterium Clostridium botulinum. It exists in seven serotypes, A through G, of which BTX-A is the most potent in paralyzing human muscle. Although other serotypes (e.g., BTX-B and BTX-F) are currently being investigated, only BTX-A is commercially available.

VTX-A causes muscle paralysis by presynaptic binding to cholinergic nerve endings and blocking the release of acetylcholine into the neuromuscular synaptic cleft. VTX-A's unique mechanism of action makes it highly specific, allowing a small amount of the toxin to have a pronounced effect. This makes it possible to obtain a therapeutic effect from small doses, making systemic effects unlikely.

In therapeutic doses, VTX-A begins to act 2-3 days after administration. Maximum muscle weakening occurs approximately 1-2 weeks after administration, when muscle fibers begin to atrophy. This process continues for up to 4 weeks. Although VTX-A leads to irreversible blockade of cholinergic nerve endings, restoration of normal muscle activity occurs as a result of renewal and healing, resorption of inactive endings, axon growth and formation of new neuromuscular synapses. The effect of VTX-A lasts for 3-6 months, after which enzymatic activity returns to the neuromuscular synapses. That is, the effect of the drug is long-lasting. However, histological changes after VTX-A administration can persist for up to 3 years. Despite this, muscle fibers are normal in activity and strength.

There are currently three BTX preparations available: Botox (manufactured by Allergan, USA), Dysport (manufactured by Ipsen, UK) and Mysbloc BTX-B (manufactured by Elan Pharmaceutical, USA). Clinically, Botox is three to four times more potent (in murine units) than Dysport and its dosage should be adjusted accordingly. Botox is available in vials and must be diluted with sterile saline before intramuscular injection. Each vial contains 100 units of C. botulinum toxin type A, 0.5 mg human albumin and 0.9 mg sodium chloride in a sterile, lyophilized, preservative-free form. 100 units of Botox is significantly less than the estimated median lethal dose (LD50) for an average 70 kg human (2500-3000 units).

BTX-A has been successfully used to treat nasal folds, crow's feet, horizontal forehead lines, neck lines, submental folds, and fine lines. It is also used for facial asymmetry or paralysis to reduce the expression of the healthy side. BTX-A is injected intramuscularly along the folds. The effect of the toxin can vary from mild weakening to complete paralysis of the muscle, depending largely on the dose administered. The clinician must determine the number of injection sites and the degree of effect after paralysis. Obviously, individual differences in muscle anatomy and function must be carefully considered.

BTX-A injections have recently begun to be used successfully as a minimally invasive procedure for temporary eyebrow lifting. In this procedure, 8-10 units of Botox are injected into the lateral and superolateral fibers of the orbicularis oculi muscle, under the lateral third or half of the eyebrow. This injection weakens the superolateral part of the orbicularis oculi muscle, leaving the lifting action of the frontalis muscle on the eyebrow intact, resulting in some lifting of the lateral part of the eyebrow. At the same time, correction of the crow's feet at the lateral angle of the eye is usually performed.

There are very few complications associated with BTX-A injections, and the effects are reversible. Reported complications include ptosis following glabella injections due to toxin migration through the orbital septum to the levator muscle, and temporary lower eyelid drooping following crow's feet correction. Brow drooping has also been reported following forehead fold correction. Furthermore, BTX-A has immunogenic properties, although no cases of antibody production have been reported following BTX-A use in therapeutic doses for cosmetic purposes.

A newer form of BTX, botulinum toxin type B, has shown promise in clinical trials. It acts much faster, is stable indefinitely in solution (can be stored), and is approved by the Food and Drug Administration for neurological use. The duration of action of this drug is not yet clear.

Significant advances have been made in minimally invasive facial fold correction and soft tissue augmentation. Although there is no single material or method for all clinical cases, physicians have a wide range of options. Meanwhile, as current methods improve, research continues to develop new materials. Injection and implantation methods are welcomed as part of the clinical arsenal for facial rejuvenation by both the medical community and the general population. Since many of the methods are new, further experience and long-term follow-up are required to ensure the expected results.

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