A Natural Bone Cement--A Laboratory Novelty Led to the Development of Revolutionary New Biomaterials
Laurence C. Chow, Shozo Takagi
In the early 1980's, Brown and Chow of the American Dental Association Health Foundation-Paffenbarger Research Center (PRC) at National Institute of Standards and Technology (NIST) conducted studies on calcium phosphates aimed at developing remineralizing pastes for repairing early dental carious lesions. Based on the solubility properties of calcium phosphates, they formulated mixtures containing tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) or TTCP and dicalcium phosphate dihydrate. Upon addition of water, these mixtures would form hydroxyapatite (HA), the major component of tooth mineral, rapidly under body temperatures. It was observed that some of the pastes became a hardened mass when left in test tubes for a few hours. Thus, the PRC scientists inadvertently discovered a new type of self-hardening cements that consists of only calcium phosphates and forms HA as the only product. By optimizing the particle size distributions of the cement ingredients, the scientists were able to develop cements with setting times of about 30 minutes and compressive strengths of 34 MPa . Powder X-ray diffraction and microscopic examinations indicated that the HA formed in these calcium phosphate cements (CPC) was in the form of very small rod-like crystals ( 0.05 mm x 0.5 mm) that are similar in size to the HA crystallites in human tooth enamel. From animal studies conducted at Northwestern University, Costantino and coworkers  found that when implanted in bone defects, CPC was gradually resorbed and replaced by new bone. Dense and porous ceramic HA materials, which have good biocompatibility, have been used clinically for repairing bone defects. However, because these materials do not resorb, they must be used in granular forms to allow a blend of soft and bone tissues to form interstitially with the HA granules to achieve stable implant-tissue integration. This has limited the use of ceramic HA for repairing small defectsrepairing small defects in bone. In contrast, because of its self-hardening and in vivo resorption properties, CPC has the potential to be useful in a much wider range of clinical applications. Continued research conducted by PRC scientists at NIST has resulted in many significant improvements in CPC. These improvements include a much shorter hardening time of 5 min , a considerably higher compressive strength of 66 MPa , and a superb wash-out resistance that allows CPC to harden in standing water . Additionally, PRC scientists discovered many other CPC formulas that also form HA as the product . In the mean time, numerous animal and human studies were conducted elsewhere in collaboration or with the help of PRC scientists on the various in vivo aspects of CPC. In July 1996, a CPC consisting of TTCP + DCPA was approved by the Food and Drug Administration for repair of cranial defects in humans, thus becoming the first material of its kind available for clinical use. CPC has become a subject of great interest to many scientists and clinicians worldwide, and several additional CPC products are now commercially available. With continuing improvements in cement properties and understanding of material-tissue interactions under various clinical situations, different CPC formulations with properties optimized for specific clinical applications are being developed.
and Takagi, S.
A Natural Bone Cement--A Laboratory Novelty Led to the Development of Revolutionary New Biomaterials, Journal of Research (NIST JRES), National Institute of Standards and Technology, Gaithersburg, MD
(Accessed May 31, 2023)