Subacute systemic toxicity assessment of β-tricalcium phosphate/carboxymethyl-chitin composite implanted in rat femur

Abstract

The efficacy of a composite of beta-tricalcium phosphate particles and carboxymethyl-chitin (beta-TCP/CM-chitin) for bone repair has already been established in animal experiments. In the present study, subacute systemic toxicity was evaluated to further assess the biological safety of the implanted composite. beta-TCP/CM-chitin (approximately 4 mg/kg and 7 mg/kg in male and female rats, respectively) was implanted for 28 days into penetrating defects (2 mm diameter) made artificially in the shaft of the right femur of rats. Sham operation groups with the defect only were prepared as controls. Haematology, blood chemistry, urinalysis, and the histopathology of 44 organs and tissues were investigated. Body weight measurements and clinical observations were performed daily throughout the study. No subacute systemic toxicity possibly caused by the implantation of beta-TCP/CM-chitin was detected. These findings indicate that beta-TCP/CM-chitin composite is a highly biocompatible bone substitute, at least with an implantation dosage of < 4-7 mg/kg.

Biocomposites and hybrid biomaterials based on calcium orthophosphates

“…Various biocomposites of calcium orthophosphates with chitosan 298,482,500,512,527,565,[645][646][647][648][649][650][651][652][653]674,675,690,695,799,807,[811][812][813][814][815][816][817][818][819][820][821][822][823][824][825][826][827][828] and chitin 232,476,612,[829][830][831][832][833] are also very popular. For example, a solutionbased method was developed to combine HA powders with chitin, in which the ceramic particles were uniformly dispersed.…”

Calcium orthophosphate-based biocomposites and hybrid biomaterials

“…Besides, they are faster resorbed in vivo. 5 Therefore, these calcium orthophosphates were used instead of HA to prepare completely biodegradable biocomposites [376][377][378][379][380][381][382][383][384][385][386][387][388][389][390][391][392][393][394]. For example, a biodegradable and osteoconductive biocomposite made of b-TCP particles and gelatin was proposed [385].…”

“…Various biocomposites of calcium orthophosphates with chitosan [239, 397, 412, 419, 435, 467, 545-549, 566, 567, 577, 582, 663, 669, 672-683] and chitin [183,394,513,[684][685][686][687][688] are also very popular. For example, a solutionbased method was developed to combine HA powders with chitin, in which the ceramic particles were uniformly dispersed [684,685].…”

Influence of carboxymethyl chitin on stability and biocompatibility of 3D nanohydroxyapatite/gelatin/carboxymethyl chitin composite for bone tissue engineering

“…18 The intravascular resorbability of carboxymethyl chitin considers it efficient in terms of biological safety which is due to its hydrolysis to an oligomer during inflammation followed by its excretion as urea. [19][20][21][22][23][24][25] Our objective was based on a biomimetic approach, in which we prepared a series of 3D scaffolds including n-HA/ gel and n-HA/gel/CMC using the solvent-casting method combined with freeze-drying and compared them, so as to test the effect of CMC (prepared by chemical modification of chitin) on the developed construct. The 3D scaffolds containing functional group for apatite nucleation, were crosslinked using glutaraldehyde in the vapor-phase, following which sodium borohydride (NaBH 4 ) was used as an excess glutaraldehyde discharger.…”