Biocompatibility and osteoplastic properties of mineral polymer composite materials based on sodium alginate, gelatin, and calcium phosphates intended for 3D-printing of the constructions for bone replacement

Bone extracellular matrix comprises a unique composite compound including the mineral and organic components. Therefore, use of biomimetic approach to the formation of tissue-engineered constructions for bone defects replacement based on composite materials containing biopolymers and calcium phosphates, as expected, can significantly improve their cyto-, biocompatibility and osteoplastic properties. The aim of the work was to study the structural features, biocompatibility and osteoplastic properties of 3D-constructions based on sodium alginate, gelatin, and two types of calcium phosphates (tricalcium phosphate and octacalcium phosphate) obtained by three-dimensional printing. The method of 3D-constructions fabrication comprised inkjet 3D-printing with hydrogel, consisted of alginate and gelatin with the addition of calcium phosphate granules, followed by freezing, freeze-drying and sterilization by y-irradiation. The structure of 3D-constructions, porosity and strength characteristics were evaluated. After the subcutaneous implantation in mice we investigated the biocompatibility of 3D-constructions during the period of up to 12 weeks. Also the osteoplastic properties of the constructions were estimated in vivo in a rat model of tibial defects. 3D printed constructions had irregular lamellar structure of sodium alginate with inclusions of spherical calcium phosphates granules. Addition of gelatin to the composite increased the porosity of constructs and significantly increased the compressive strength meanwhile practically had no effect on the ultimate strain value. In results of subcutaneous in vivo tests 3D printed constructions demonstrated perfect prolonged biocompatibility. The highest rate of biodegradation was noticed for implants containing octacalcium phosphate. All of the studied 3D-scaffolds had osteoconductive potential, more pronounced according to the number of examined histological parameters in those, made from sodium alginate, gelatin and octacalcium phosphate. The data showed the feasibility and prospect of using three-component mineral polymer composite materials based on alginate, gelatin and octacalcium phosphate as an “ink” for 3D printing of bone grafting constructions intended for implantation in bone defects.

3D printing, sodium alginate, gelatin, tricalcium phosphate, octacalcium phosphate, bone substitutes, bone defects replacement