1. Basic Physical and Chemical Properties of the Material
The chemical molecular formula of Calcium-Hydroxylapatite is Ca₁₀(PO₄)₆(OH)₂. As a type of calcium-phosphate bioceramic material, it has a calcium-phosphate molar ratio of approximately 1.67 and a hexagonal crystal structure, which is basically consistent with the inorganic mineral composition of human natural bone tissue. Physical and chemical parameters of the material, such as powder particle size, particle morphology, crystallinity, pore structure and purity, will directly affect the biocompatibility, degradation behavior and in vivo tissue response performance of the material.
In the development of medical devices, CaHA substrates in various forms such as powder, granules, porous bulk and coating can be obtained by adjusting the synthesis process. There are clear structural differences between CaHA products for different application directions: CaHA products used in orthopedics and stomatology are mostly irregular porous particles or bulk scaffolds with a particle size of usually hundreds of micrometers, which are mainly used to provide a supporting carrier for bone tissue growth. For compliant medical aesthetic-grade CaHA products developed for soft tissue filling scenarios, they are mostly smooth-surface microspheres with a particle size of tens of micrometers, uniformly dispersed in an absorbable gel carrier to reduce tissue trauma risk during injection.
2. Basic Properties as a Biomaterial
Existing in vitro and animal experimental studies show that synthetic Calcium-Hydroxylapatite has good biocompatibility, low antigenicity, and will not cause obvious immune rejection after being implanted into the body.
In the scenario of bone repair, CaHA materials exhibit osteoconductive properties, providing a scaffold environment for the adhesion and proliferation of bone tissue cells. Porous-configuration Calcium-Hydroxylapatite can support the ingrowth of new bone tissue into the internal pores of the material. The material will gradually dissolve and degrade along with the in vivo metabolic process, and calcium and phosphorus ions will participate in the normal mineral metabolism cycle of the body.
In the direction of soft tissue-related implantation, raw materials represented by spherical micron-sized CaHA particles are often compounded with aqueous gel carriers such as carboxymethyl cellulose (CMC) to construct injectable implantation systems. After implantation, the gel carrier is gradually metabolized and absorbed, and CaHA particles remain inside the tissue, acting as a physical scaffold and signal source to interact with surrounding fibroblasts and macrophages. Existing literature observations indicate that it can induce the formation of surrounding connective tissue. The related biological response results are affected by conditions such as particle size, morphology and crystallinity, and individual differences exist.
Note: In vitro and animal experimental results at the material level are not equivalent to the clinical effects of finished medical devices. Only finished products that have completed the full registration review and obtained the medical device registration certificate can be used for human clinical practice.
3. Development and Application Directions in the Field of Medical Devices
As a substrate, Calcium-Hydroxylapatite is mainly developed and transformed into products in the two major medical device tracks of bone repair and soft tissue implantation. All related products need to follow medical device regulations to complete full-chain verification.
Bone Repair Implantable Medical Devices
Calcium-Hydroxylapatite is one of the classic substrates for bone defect repair materials. It can be processed into particles or porous bulk, and can also be sprayed on the surface of metal implants as a coating. Its main R&D directions include bone defect filling, surface modification of orthopedic implants, and oral and maxillofacial bone tissue repair. Porous CaHA substrates are mainly used for the development of repair in non-load-bearing bone defect sites. The indications of approved products are mostly limited to "non-load-bearing bone defect filling", which is used for filling and repairing bone defects during orthopedic surgery to assist the healing of bone tissue. In the field of stomatology, related approved products are mainly used in scenarios such as alveolar bone defect filling and orbital implant placement, adapting to the clinical repair needs of oral surgery and ophthalmology to help restore the basic morphology and function of local tissues.
Since the porosity and pore size of the material will affect the bone tissue ingrowth effect and material degradation rate, a series of verification tests such as mechanics, biosafety, and in vivo animal osteogenesis are required to be completed at the product development stage.
Soft Tissue Filling Implantable Medical Devices
Since 2025, two injectable Calcium-Hydroxylapatite microsphere facial dermal filler products have officially obtained Class III medical device registration certifications in China. Among them, the first domestically approved product clearly limits its indication to subcutaneous injection in the nasolabial fold area, for correcting moderate to severe nasolabial folds. The first imported approved product clearly limits the applicable scenario of supraperiosteal injection on the face, for improving the mandibular contour of patients with moderate mandibular retrusion.
The compounding of Calcium-Hydroxylapatite and gel carrier is an important technical route for soft tissue filling implantable medical devices. This type of product belongs to Class III medical devices, which has extremely strict requirements for raw material purity, particle morphology, particle size distribution and sterility control. The R&D priorities in this direction focus on particle parameter optimization, carrier formula debugging, in vivo volume maintenance performance, histocompatibility, degradation behavior and other aspects. Raw material screening is the key link of product development. Sterile spherical Calcium-Hydroxylapatite (CaHA) with a purity of 99% and a particle size of 25-45μm is an ideal choice.
4. Compliance Points for R&D and Production
Calcium-Hydroxylapatite is only a substrate raw material for medical device production. The raw material itself cannot be directly used on the human body as a finished product. To develop implantable medical devices with this substrate, it is necessary to carry out work in accordance with relevant Chinese medical device regulations and industry standards:
Raw Material End: It is necessary to establish a raw material quality control system to control key indicators such as chemical purity, microscopic morphology, particle size distribution, microorganisms and endotoxin, and meet the requirements of YY/T 1558 and GB 23101.6 series of national standards.
Product Development: Complete full sets of verifications including physical and chemical properties, sterility, biocompatibility evaluation, in vivo animal implantation tests, etc., and clarify the product's scope of application, contraindications and usage restrictions.
Registration and Marketing: Complete the registration review in accordance with the requirements for Class III medical devices, and obtain the registration certificate before production and marketing. The listed finished products must be used clinically strictly in accordance with the scope of application specified in the registration, and no off-label application is allowed.
5. Summary
Calcium-Hydroxylapatite (CaHA) is a biomimetic calcium-phosphate bioceramic substrate. Relying on its chemical composition similar to the minerals of human hard tissue, it has extensive development value in the scientific research and manufacturing fields of bone repair and soft tissue implantable medical devices. However, the material performance is highly dependent on the preparation process and microscopic parameters. The raw material is not equivalent to a medical device-grade finished product. From the substrate to the finished product that can be used on the human body, a complete process of material screening, formula development, safety verification and registration is required.
Disclaimer: This article is only a material science popularization and does not constitute any product efficacy promise. The use of all medical Calcium-Hydroxylapatite implantable devices is subject to the contents specified in the approved medical device registration certificate.
References
[1] YY/T 1558.3-2017，外科植入物 磷酸钙 第 3 部分：羟基磷灰石和 β 磷酸三钙骨替代物 [S]. 国家药品监督管理局医疗器械技术审评中心. https://www.cmde.org.cn/hbpdf/YY1558.3-2017.pdf?type=pc国家药品监...
[2] Karatas E, Koc K, Yılmaz M, et al. Characterization and Comparative Investigation of Hydroxyapatite/Carboxymethyl Cellulose (CaHA/CMC) Matrix for Soft Tissue Augmentation in a Rat Model[J]. ACS Omega,2024,9(31):31586 31600. https://pmc.ncbi.nlm.nih.gov/articles/PMC11270726/pdf/ao4c01503.pdfPMC
[3] Hubbard W. Injectable Calcium Hydroxylapatite Implants: Biocompatibility[R]. Cytophil Inc. https://cytophil.com/wp content/uploads/2021/06/SM 08 033 A Attachment I Injectable CaHA Implants Biocompatibility 00.pdf
[4] Woolery-Lloyd L H. Calcium Hydroxylapatite in Regenerative Aesthetics: Mechanistic Insights and Mode of Action[J]. Aesthetic Surgery Journal,2025,45(4):393-406. https://academic.oup.com/asj/article/45/4/393/7810945Oxford Aca...
[5] Lebre F, Sato Y, Bringensparr C, et al. Particle shape dictates NLRP3 inflammasome activation by hydroxyapatite biomaterials[J]. Acta Biomaterialia,2017,57:423-434.