Calcium hydroxylapatite (CaHA) “Radiesse as an example” is a high temperature fired bioceramic whose main component is calcium hydroxylapatite microcrystalline spheres with a diameter of 25-45 micrometers. In addition to containing 30% CaHA microspheres, the remaining 70% is composed of a gel matrix consisting mainly of water (sterile water used for injections), glycerin, and sodium carboxymethylcellulose (CMC). The outer layer of the microcrystalline porcelain is covered by a viscous gel substance, which will form a skeleton when it enters the tissues and stimulate the proliferation of collagen to climb on the skeleton. It has good biocompatibility, is not easy to be allergic to, and is highly safe, with a short recovery period after the treatment, small wounds, and no need for special enhanced moisturizing. The role of CaHA microspheres here is threefold: (1) filling, (2) stimulation of collagen and elastin production, and (3) as well as skin tightening effect through fibroblast action.

　　1.Hydroxyapatite microspheres Appearance:

　　Characteristics: 25-45 micron particles are small and have a smooth surface, which reduces the incidence of skin trauma and serious side effects (including granulomas) during the injection process. This size is optimal for avoiding macrophage phagocytosis, and few macrophages were observed at the injection site.

　　2. Comparison with hyaluronic acid fillers (significant tightening and lifting effect, long-lasting)

　　Compared with injectable implants such as hyaluronic acid, which are commonly used nowadays, Radiesse has a longer maintenance potency and has a filling function to improve skin depressions and lack of fullness.

　　3. Degradation mechanism (particle size):

　　Fibroblasts are unable to endocytose 25-45 micron microspheres and are therefore activated to release pH-lowering cytokines. As tissue pH is lowered, CaHA dissolves into calcium and phosphate ions. Calcium ions activate fibroblasts through known pathways. On the other hand, when the microsphere is smaller than 15 microns enough to be phagocytosed, it is engulfed by macrophages and the particles are further degraded within the phagocytes.

　　4. History of Radiesse development

　　In the early 1990s, a CaHA product called Coaptite (developed by Bristol-Myers Squibb) was used for the treatment of urinary incontinence.In 1999, this technology was acquired by BioForm Medical in the U.S.A. and was further developed for facial indications until the first patient was treated in 2001.In 2003, the FDA approved a product called In 2003, the FDA approved a product called Radiance, which was later renamed RADIESSE. In the aesthetic field, RADIESSE was first approved as a medical device by the EMA in 2004. 2006 saw the CE marking of its use in contouring and reconstructive surgery for deep dermal and subcutaneous soft tissue filling of the face. That same year, the FDA approved RADIESSE for the treatment of moderate to severe wrinkles and folds, such as nasolabial folds, as well as for the restoration and/or correction of lipoatrophy in patients with the Human Immunodeficiency Virus (HIV).In 2015, the FDA also approved RADIESSE for non-facial indications, such as enlargement of the hands.In 2009, the manufacturing company, BioForm Medical, was acquired by the German In 2009, the manufacturing company, BioForm Medical, was acquired by the German pharmaceutical company, Merz Pharma, and RADIESSE was re-launched in several markets around the world, leading to a significant increase in sales.RADIESSE's patented formula resulted in a decade-long monopoly.In 2013, the market for CaHA products was opened up to other manufacturers. Since the introduction of CaHA products in 2003, the formulation remained unchanged until 2016, when a lidocaine-ized version was released in the U.S. market and subsequently rolled out globally. By 2018, at least two other manufacturers had begun producing CaHA products to RADIESSE's specifications. As a result, RADIESSE has a very rich clinical use in soft tissue internal filling applications.

　　5. News from China

　　Merz is expected to launch the first hydroxyapatite microsphere filler in China.

　　6. Summary

　　In the field of medical aesthetics, the filler materials on the market are mainly divided into two categories: synthetic materials such as silicone, PMMA, polyacrylamide hydrogel, polylactic acid, etc.; biomaterials such as collagen, hyaluronic acid, autologous fat, etc. In 2006, through the U.S. FDA-approved Radiesse Porcelain Microcrystalline Porcelain is considered to be an ideal semi-solid non-surgical facial filler materials, with good biocompatibility, injection sites will form new natural tissues, and the injection site will form new natural tissues. Radiesse is considered an ideal semi-solid non-surgical facial filler with the advantages of good biocompatibility, formation of new natural tissues at the injection site, longer effect maintenance time than other fillers, and even comparable to short-acting hyaluronic acid products in terms of safety.Radiesse Microcrystalline Porcelain consists of 70% semi-solid gel and 30% calcium hydroxyapatite microspheres, with the latter being a built-in component of the body, and the former consisting of calcium hydroxyapatite microspheres with a size of 25-45 μm suspended in a gel carrier made of water and glycerol as the main ingredients. The former is formed by suspending 25~45μm calcium hydroxyapatite microspheres in a gel carrier with water and glycerol as the main components, and the gel structure is adjusted by adding a small amount of sodium carboxymethylcellulose.2020 September 30, 2020 published “Summary of the results of the second batch of 2020 classification and definition of medical device products” shows that, among the periosteum filler microplasty products used for facial cosmetic treatment, the “mandibular periosteum filler” contains calcium hydroxyapatite microspheres, sodium hyaluronate and water. Hydroxyapatite bioceramics for mandibular periosteum filling” should be managed as Class III devices, with the classification code 13-09.The calcium hydroxyapatite microspheres in this product are suspended in the gel carrier composed of sodium hyaluronate and water, which can be fixed in the injection site for a period of time to provide support, and then be absorbed and metabolized by the human body.