Preclinical safety and efficacy evaluation of ‘BioCaS’ bioactive calcium sulfate bone cement

Abstract

A new bioactive calcium sulfate-based formulation (named 'BioCaS') has been developed for bone filler applications. This is a self-setting injectable cement where the preset form comprises bassanite obtained from the uniform submicron-sized precursor crystals of gypsum, modified with hydrogen orthophosphate ions. The results of the safety and efficacy evaluation of BioCaS cement, done as per the International Standards and guidelines, are presented in this paper. The study plan consisted of in vitro screening tests of cytotoxicity and haemolysis and in vivo biocompatibility evaluation, including an acute systemic toxicity test (in mice), an intracutaneous reactivity test (in rabbits), a pyrogen test (in rabbits) and a maximization sensitization test (in guinea pigs). The efficacy of the material in healing bone defects was investigated by implanting it in artificially created defects in rabbit femora, with clinically established hydroxyapatite porous ceramic as the control, followed by histological analysis at 12, 26 and 52 weeks. Set BioCaS cement consisted of hydrogen orthophosphate incorporating low-dimensional gypsum crystal lattices, the bioactivity of which has been identified by immersion in simulated body fluid. BioCaS was proved to be non-cytotoxic and non-haemolytic in the screening tests. In the live/dead assay, human osteoblast-like human osteosarcoma cells adhered well and spread on the surface of the material, attaining typical morphology and affirming the bone cell compatibility of the material. In the biocompatibility evaluation there were no acute systemic effects and the material proved non-pyrogenic. There was no intracutaneous erythemic or oedematous reactivity and no hypersensitivity observed in the Magnusson-Kligman method. The material satisfied the biocompatibility requirements. Bone implantation study revealed BioCaS to be osteoconductive and its efficacy of healing the experimental bone defects in rabbit femora is on a par with that of hydroxyapatite ceramic. The material resorbed at a pace matching that of new bone formation. This property of osteotransductivity will help the defect to heal and gain strength faster.

A Bioactive Degradable Composite Bone Cement Based on Calcium Sulfate and Magnesium Polyphosphate

“…As shown in Figure 5a, the cell viability of each concentration exceeded 100% on days 1, 3, and 5, suggesting a promoting effect on cell proliferation. Actually, numerous studies showed the cell proliferation ability of CSC was inferior to that of the control group, likely attributed to acidic byproducts generated during its degradation [29,[43][44][45][46][47]. It can be inferred that the biocompatibility of CS/MPP/C 3 S composite bone cement was greatly improved.…”

Advanced applications of strontium-containing biomaterials in bone tissue engineering

“…As a BM that is widely used in clinical practice, calcium sulfate (CaSO 4 ) has various advantages, including good biocompatibility and degradability, sufficient sources, convenient sterilization, and other characteristics [ 217 ]. CaSO 4 cement has been approved by the US Food and Drug Administration (FDA) to be used in clinical bone defect treatment [ 218 , 219 ]. In the body, CaSO 4 can be completely degraded and absorbed through humoral-mediated dissolution and cell-mediated phagocytosis and does not have any significant impacts on Ca levels in blood [ 218 ].…”

Calcium silicate and calcium aluminate cements for dentistry reviewed

“…Animal tests have been formed to gain histological responses to the cements using the teeth of subject dogs, 56,109,[211][212][213][214][215][216][217][218] ferrets, 219 rats, 109,[220][221][222][223] monkeys, [224][225][226] and the bones of rats, 227,228 or rabbits. 85,[229][230][231][232] The advantage of animal testing is using multiple teeth and being able to microscopically examine the healing tissues. Notably, the overall trend in medical device development is to minimize animal testing and use more tissue-specific tests.…”