Synthesis of an Orthopedic Cement by the Addition of Anhydrous Calcium Hydrogen Phosphate to Calcium Sulfate Hemihydrate

Abstract

Commercially available calcium sulfate hemihydrate (CSH) powders were mixed with anhydrous calcium hydrogen phosphate (monetite) in order to develop a novel resorbable orthopedic cement. The setting solution, distilled water, converted the CSH into gypsum as proven by an X-ray diffraction. This conversion into gypsum is what gives the cement its high compressive strength. The addition of monetite gives the cement a high bioresorbablity and remodeling ability that is not present in the pure CSH cements on the market today. Instead of merely dissolving into powder when placed in body fluids like CSH cements, the phosphate-enhanced cement in vivo may convert into apatitic bone-like structures.

Introduction

Thanks to the considerable advances in orthopedic surgery in the past twenty years, surgeons today are faced with many different techniques and substances with which to fill and correct bone defects. The most common treatment of choice for these corrections, however, despite new technologies, is autologous bone grafting. This is a process in which the surgeon scrapes bone cells from the patient's hipbone to place in the defect site. This treatment displays three main characteristics associated with the bone healing process: osteoconduction (the ability of materials to serve as a scaffold for new bone growth), osteoinduction (the ability of materials to promote and/or stimulate the formation of new bone), and osteogeneration (the ability to directly create bone tissue) (Smith & Smith, 2000). However, there are also disadvantages to the bone grafting method. Pain, infection, or nerve damage is reported by 10-25% of all patients and there may not be a sufficient amount of material available at the harvesting site, as often is the case in children. For the surgeon, disadvantages include a much longer operation time (Bloemers, Blokhuis, Patka, Bakker, Wippermann, & Haarman, 2003). Using an artificial bone substitute in place of autologous bone grafting has helped to circumvent these difficulties and various artificial bone substitutes have been developed for this purpose.

Calcium sulfate hemihydrate (CSH) is used as an artificial bone substitute and is the most prevalent orthopedic cement in the United States market today, since its FDA approval in 2001. With the addition of a setting solution of water or saline, the CSH converts into a calcium sulfate dihydrate, more commonly known as gypsum. Gypsum shows good compressive strength results, however it does not maintain that strength for long after it is placed in body fluid. Gypsum in vivo does not withstand the effects of body fluid and dissolves into powder within the first few months after the surgery, before strong new bone can replace it. The optimal cement would uphold the mechanical strength during the stages of cellular resorption in the first three to four months but would be gradually replaced by new bone at the defect site within a year of the operation (Tas, 2004).

When synthesizing a novel orthopedic substitute, one must consider many various factors including toxicity, pH, and body temperature. The elements and components of a cement can not contain materials that could harm the body. The material should ideally contain certain components similar to those of natural bone -- mainly calcium and phosphorous, and secondarily carbon, hydrogen, and oxygen. The calcium to phosphorous ratio in adult bones is normally around the number 1.67. Likewise, the material cannot alter the pH of the blood (pH=7.4). Having a substitute that is more alkaline or more acidic than 7.4 would alter the pH of the blood and result in catastrophic and often fatal consequences. Therefore, calcium hydroxide (Ca(OH)2), although containing elements of natural bone, would not be a useful chemical in a bone cement because it is such a strong base. The material must also be able to remain solid at the normal human body temperature of 37 ˚C (Joschek, Nies, Krotz, & Gopferich, 2000).

An addition of calcium-phosphate to CSH may synthesize a cement with a strength comparable to that of pure CSH, but with a more ideal bioresorbability rate. . The addition of phosphate into the CSH mixture may also produce more apatitic growth because the cement would better imitate the composition of natural bone, and thus more natural bone would create more strength. The cement would also be much more slowly absorbed into the body as it is replaced by natural bone, ideally within six months to a year after the operation. It is hypothesized that by adding CaHPO4 in proper ratios to CSH, a more ideal bioresorbability and bioactivity rate with a comparable compressive strength will be achieved.

Methods and Materials

Anhydrous calcium hydrogen phosphate (CaHPO4) was measured out in ratios of 5%, 10%, and 33% compared to Calcium sulfate hemihydrate (CSH). The powders were then mixed together using a mortar and pestle in wet form in order to ensure that the powders are completely mixed together. To do this "wet" mixture, enough ethanol must be used to have a liquid-to-powder ratio equal to 0.50. The ethanol and powders were mixed until a liquid paste was formed. The ethanol mixture was then placed in a 60 Ñ"C oven for 90 minutes to allow for the ethanol to completely evaporate. The setting solution of distilled water was added into the powder mixture using the liquid-to-powder mass ratio of 0.40 after the ethanol had fully evaporated. The water and CaHPO4-doped CSH powder was then mixed thoroughly for 3 minutes until a workable paste was formed. The paste was then put in a steel die to be pressed at 2,000 psi for approximately 8 minutes. Within this time, a perfect cylindrical pellet formed. The pellet must be removed from the steel die, and then placed in a 37 Ñ"C oven to dry overnight.

Several tests were performed on the samples in order to determine the effectiveness of the product. To determine its compressive strength, a perfectly cylindrical pellet is placed between two steel plates (2 centimeters thick) and loaded into the Instron Compression Machine. This machine would then slowly increases the pressure on the cylinders by pressing down on them eventually reaching a force of almost 13,800 N. The strength of the material was calculated by comparing the displacement relevant to the force applied. X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) tests were performed on the control samples as well as each of the doped samples to gain a better understanding of the composition and crystal structures of the samples. To perform XRD and FTIR tests, the pellet was crushed into a fine powder using a mortar and pestle. To determine how a sample would react within the setting