Adding alginic acid to calcium phosphate cement has been shown to improve compressive strength and porosity of artificial bones, promoting faster and more effective bone repair and regeneration.
How to not break under pressure? While we ask this question in the face of stressful situations, so do our bones. Though known to be tough and hardy, bones will bend under strain and in some cases, snap if the pressure is too great or too sudden. In such a case, bones call on their ability to self-heal and regenerate by a cycle of bone resorption and bone formation. However, if damage to the bone is caused by a disease or severe injury, it becomes difficult for the body to repair itself, thus requiring a substitute to replace the missing bone. This is where artificial bones come into play.
Initially, artificial bones were made of materials like metals and solid ceramics to mimic the strength of natural bones. However, the rigidity and poor biocompatibility of these materials prevent synthetic bones from blending into bone tissues. In recent years, clinicians have begun to use a new biopolymer called calcium phosphate cement as a common bone replacement material to build better bones. With its self-setting nature, calcium phosphate cement can be injected into a patient, thus making it non-invasive. But this material is still limited as it has a dense microstructure that makes it difficult for cells to enter, thereby preventing new bone growth.
In a new collaborative study by researchers from the Graduate School of Medicine and the Graduate School of Engineering of Osaka City University, it has been found that mixing alginic acid with calcium phosphate cement can significantly improve the setting time and compressive strength of artificial bones. Incorporating alginic acid can also increase the porosity of the biomaterial, thus permitting the entry of cells to a defective area and grow new bone.
"Artificial bones can support broken bones, but they do not replace our own bones and remain in the body as a foreign object,” said Graduate Student and first author Akiyoshi Shimatani.
“To solve this problem, we have developed an artificial bone in collaboration Professor Yoshiyuki Yokogawa and his team from [Osaka City University] Faculty of Engineering, which is sticky, hard to break, and replaces the body’s own bone,” continued Associate Professor Hiromitsu Toyoda of the university’s Department of Orthopaedic Surgery.
Alginic acid has long been used in the medical field for cell immobilisation, drug delivery, and wound dressing. However, it has not been studied in conjunction with calcium phosphate cement to facilitate bone repair. Past studies primarily focused on other biopolymers like gelatine, collagen, and chitosan, even though the degradability and cross-linking characteristics of alginic acid show promise to improve on the dense and poor mechanical properties of calcium phosphate cement.
To fill this gap, Shimatani and colleagues embarked on their investigation to determine whether mixing low viscosity alginic acid with calcium phosphate cement can promote interconnected porosity in the cement and enhance bone replacement. To do this, the team examined a series of calcium phosphate cement-alginate compounds with varying amounts of alginic acid.
Based on in vitro analysis, it was found that increasing the amount of alginic acid in the calcium phosphate cement sped up the time needed for the material to set. Scanning electron microscopy also showed that compounds with increased alginic acid had more pores and less density, appropriately addressing the limitations of past models. Because their work hopes to be brought into clinical practice, the researchers proceeded to test their mixture in vivo.
Using rabbit models, the scientists injected calcium phosphate cement with varying levels of alginic acid into holes created on their femurs. After six weeks, X-ray and micro-CT analysis revealed that femurs injected with cement compounds containing elevated levels of low viscosity alginic acid exhibited more degradation and bone formation in comparison to the control group. They also observed shortened setting time and greater compressive strength, thus demonstrating alginic acid’s potential as a promising additive.
As the first study to demonstrate the benefits of incorporating low viscosity alginic acid to enhance the biological performance of calcium phosphate cement, their findings are expected to advance bone tissue engineering. Associate Professor Hiromitsu Toyoda and colleagues are hopeful that their work can “become a new option for artificial bones.”
Source: Shimatani et al. (2021). A bone replacement-type calcium phosphate cement that becomes more porous in vivo by incorporating a degradable polymer. Journal of Material Sciences: Materials in Medicine, 32, 77.