Before the invention of the syringe, there was nothing to talk about: in 1844, Francis Rynd, an Irish physician, invented the hollow needle; in 1853, Charles Pravaz, a French surgeon, and Alexander Wood, a Scottish physician, each invented the needle and syringe for medical use at the same time. After that, the history of cosmetic injection is based on the development of material science. It can be said that the history of cosmetic injection is also the history of cosmetic injection materials, and the abandonment of old materials and the development and application of new materials constitute the overall framework of cosmetic injection development. The ideal injectable filler material should be safe and reliable, with good biological adaptability, no teratogenic carcinogenicity, no infection, no autoimmune reaction (no skin test), no wandering after injection, the effect can be maintained for more than several years after injection, soft to the touch, natural appearance, preferably cheaper, and easy to use and store, the treatment effect should be reversible, and can be easily removed and degraded when not needed No side effects. The development of cosmetic injections has been walking on the road of exploring this ideal material, is constantly learning from mistakes, the process of moving forward, many of the new discoveries at the beginning of the cheerful, and finally ended up with serious complications, so in a new material new method of birth, we can not blindly superstitious manufacturers of propaganda, must be examined with a skeptical eye, to test the time. First, the history of the development of injectable filler materials The development of injectable cosmetic filler materials can be broadly divided into three periods, but there is an intersection between the different periods, without absolute boundaries. 1, the period of immunogenic materials (representative: liquid paraffin) The saga of injectable fillers began in 1830, when the German chemist Baron Karl Ludwig von Reichenbach first invented the preparation of a substance named “paraffin”, initially used in industry. 1899 Robert Gersuny, a Viennese physician, first injected liquid paraffin into the human body to treat testicular defects caused by tuberculosis. This is probably the earliest officially documented cosmetic injection procedure. Due to the limitations of the time and the ignorance of immunology, liquid paraffin wax was widely welcomed by the medical profession at that time and its indications were soon extended to other cosmetic applications such as injectable breast augmentation and nasal fillers, and the use of liquid paraffin wax and some other inorganic oils in the cosmetic industry continued until World War II. However, after its first complication was reported in 1901, in 1911, Dr. Kolle summarized a series of sequelae caused by paraffin injections, mainly inflammation, infection, embolism, and yellow patches of skin at the injection site. The most famous incident of disfigurement by paraffin injection occurred with the Duchess of Marlborough, an American-born star who, after receiving a paraffin injection into the back of her nose, the paraffin wandered into her cheek and a paraffinoma (i.e., granuloma) formed on her entire face. Due to the limitations of immunological development, the choice of filler materials in those days was quite blind. To avoid complications after paraffin injections, materials such as beeswax, lanolin, vegetable oil, petroleum jelly and their mixtures were used for injectable fillers and all were discarded because of the same problems. The last tragedy was reported by the London Daily Telegraph on November 11, 2008, in which a Korean woman who received silicone injections at a beauty hospital took home the unused material and then blindly replenished the injections herself. When she ran out of the remaining silicone, she replaced it with cooking vegetable oil, resulting in severe disfigurement. With the development of immunology, the principle of foreign body rejection of paraffin and other materials was recognized: when paraffin is injected into human tissues, it is widely distributed in tissues in the form of small lipid droplets, causing rejection of the organism, and a large number of phagocytes are seen microscopically around the lipid droplets, and local tissue fibrovascular hyaline degeneration, necrosis, fibroblast proliferation and scar formation of the so-called “paraffinoma”. Clinically, local edema, scar formation, sometimes secondary to skin breakdown, formation of chronic ulcers or even carcinoma, and enlarged lymph nodes with visible hydrocarbon components were observed. Then, people began to look for more stable filling materials. 2.Permanent material period (Representative: liquid silicone, polyacrylamide hydrogel, Avef) In the 1940s, the use of liquid silicone injection for breast augmentation was first started in Japan, and began to become popular around the world 20 years later. Due to the stable nature of silicone, it has been thought to be a safer and more reliable injection material. Polyacrylamide hydrogel, on the other hand, was the secret weapon of the KGB agents in the former Soviet Union, and its miracle was that it could easily and quickly change the user’s appearance until after the collapse of the Soviet Union, when it was declassified and exported by Ukraine and other former Soviet member states. The most famous product is “Ingelfahrer”, i.e. “Omnidene”. Although liquid silicone and polyacrylamide hydrogels are physically stable and not too immunogenic, they have many advantages such as elasticity, hydrophilicity, heat resistance, acid resistance and non-irritation, but they cannot be fused with human tissues and will not be degraded or removed when left in the body for a long time. If injected properly, they can coexist peacefully with the body for a long time under the isolation of the envelope, but after a few or even more years, they will gradually deteriorate and cause a series of adverse reactions. More often than not, it is early after injection that the phenomenon of wandering around occurs, and later a series of complications such as fistula, ulceration, infection, and in severe cases, eventually the failure of internal organs and even death can occur. Therefore, as early as 1964, the U.S. Food and Drug Administration (Food?and?Drug?Administration, hereinafter referred to as the FDA) will be defined as a drug to restrict its use of liquid silicone, 1976 Medical Device Amendment also prohibited the use of liquid silicone as a device, in 1979 the FDA and the American College of Physicians condemned liquid silicone for injection. Now medical-grade silicone can only be used for the treatment of retinal detachment, and it is illegal to use for cosmetic purposes. China was once out of line with the world for some historical reasons, and after being in line with the new world, due to some blind perceptions and the temptation of market interests, in 1997, the polyacrylamide hydrogel product “Ingelfahrer” was introduced as a high-tech product, and developed its cottage version – “Omedin”. The product was introduced as a high-tech product in 1997 and developed its cottage version – “Omnidene”. Because of its quick effect, small trauma, plasticity, coupled with the gap in the market and the excessive propaganda of certain businesses, Omnidene was soon accepted by the majority of “beauty seekers” in China. Nowadays, many hospitals that have been doing their best to promote and inject a large number of Omnidine have become “designated units for Omnidine removal”. The PMMA microspheres can be quickly wrapped in a complete package of slender fibrous membranes when injected into the plastic parts, so they will not move and degrade, so the risk of injection is much lower compared to liquid silicone and polyacrylamide. The risk of injection is therefore much lower than that of liquid silicone and polyacrylamide hydrogel, but there are still many disadvantages such as the tendency to induce granulomas. The biggest disadvantage of permanent materials is that they do not “change with the times”, leaving aside the problem of the wandering nature of some materials. It is important to understand that the human body is a delicate balance of constant change, even if the injection early to obtain satisfactory results, as the body continues to change, permanent materials in the form of “eternal unchanging” has always existed in the body, which is a discordant factor, but also a security risk, with the passage of time, more and more problems will As time passes, more and more problems will emerge. With the rapid growth of more safe and reliable short-acting filler materials such as collagen and hyaluronic acid, and gradually occupy the main share of injectable filler materials, in December 2008, the U.S. company Artes, a manufacturer of Abbev, filed for bankruptcy protection, this event has triggered the global industry to focus again on the safety of permanent fillers and market prospects, and also basically announced the end of the ” Permanent material period” the end. 3, short-acting materials period (representative: collagen, hyaluronic acid) collagen period bovine collagen for the improvement of age-related wrinkles clinical trials began in 1977-1978, after six years of clinical evidence, the first collagen filler product Zyderm was approved by the FDA in 1981, and opened the prelude to the period of short-acting materials. However, the early bovine collagen products had problems such as too short maintenance time (only 3 months), retained some immunogenicity despite purification, had to be skin tested before injection, but still might have systemic immune symptoms such as fever and itchy rash after injection, and were expensive, which did not have too obvious advantages over the long-acting injectable materials of the same period, thus limiting their clinical application. Collagen has been developed in response to the improvement of the above two major deficiencies: (1) Removal of immunogenic substances (including the use of collagen from other sources) by a newer process, which has evolved as follows: (1) bovine collagen → allogeneic human collagen (cadaveric origin) → collagen cultured from autologous skin → collagen cultured from allogeneic skin; (2) bovine collagen → porcine collagen. (2) Improve the preparation process and increase the degree of molecular cross-linking to reduce the absorption rate in the body and increase the filling time. With the introduction of more and better collagen products, collagen (mainly bovine collagen) has been widely used in minimally invasive facial filler plastic surgery in the United States and Europe from the late 1980s to the early 1990s. However, since allogeneic sources of protein always contain some unknown risks, the spread of mad cow disease in the mid to late 1990s dealt a big blow to the promotion of collagen, and considering the possibility of more unknown pathogens present in allogeneic proteins, the use of collagen has been controlled in Europe and America, and the use of human collagen is still difficult to be popularized due to ethical or biotechnological restrictions. Therefore, the collagen products currently available on the market are mainly the safer porcine collagen products. With the development of safer and more effective hyaluronic acid-based materials, the market for collagen products gradually began to shrink. Hyaluronic acid is an acidic mucopolysaccharide, which was first isolated from the vitreous humor of bull’s eye by Meyer, a professor of ophthalmology at Columbia University in 1934. water content), it has been widely used in the field of cosmetics and skin care products. With the development of bioengineering, the use of bacteria to synthesize hyaluronic acid has provided higher quality hyaluronic acid, and the development of cross-linking technology has made the structure of hyaluronic acid more stable, thus qualifying it for use as an injectable filler. The earliest hyaluronic acid injectable product was developed and manufactured by Q-Med, Sweden, and was approved by CE in 1996, by FDA in 2003, and by the State Food and Drug Administration (SFDA) in 2008. Hyaluronic acid filler has become the most widely used injectable filler in clinical practice with the advantages of higher safety, more selective models, more powerful hydration and isotonic degradation.