Nowadays bone defects and age related orthopedic disorders have become a critical public health issue. New tissue engineering strategies allowed the development of different technique for the de novo generation of bone tissue, including the use of autologous bone forming cells. In this case, biocompatible three-dimensional porous scaffolds materials are essential to mimic the native bone tissue microenvironment, giving a structural support and, at the same time, allow the transportation of nutrients and oxygen to the growing cells. To this purpose, this work is based on the development of new solid alginate foams with a suitable microporosity to support and enhance growth and osteogenic differentiation of human Mesenchymal Stem cells (hMSCs). Macroporous alginate foams (MAFs) were formulated by freeze-drying of hydrogels prepared by internal gelation [1] using glucono-?-lactone (GDL) and strontium carbonate. Strontium is well known as bone anabolic agent and in this case it was used with a double function: (I) cross-linking agent for the alginate chains and (II) enhancer of the osteogenic differentiation of mesenchymal stem cells (MSCs) thanks to an in situ release from the foam [2]. To obtain a macroporous uniform structure, sodium bicarbonate and pluronic F127 were added as foaming agents and foam stabilizer, respectively. The MAFs were tested for functional characteristics including mechanical strength, porous structure, stability, water content and swelling. A preliminary formulative study was carried out to define the optimal conditions to produce MAFs with different shapes and size. The acidic environment, created by the hydrolysis of GDL, promotes dissolution of strontium carbonate and development of CO2 from sodium bicarbonate, generating the physical crosslinking and the microporosity in only one step. After the freeze-drying process, MAFs were soft, flexible, elegant in appearance, non-brittle in nature and, due to their porous nature, have proved to be suitable for cell migration whilst still maintaining their physical integrity. Porosity was evaluated by scanning electron microscopy (SEM) showing interconnected pores with a well-defined size range. Furthermore, mechanical characterization demonstrated that the MAFs were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed bone tissue. In conclusion, MAFs seems to be a very promising three-dimensional scaffold for in vitro bone cell growth. Further studies are in progress to evaluate the effect of the scaffold and of Sr2+ ions released in the environment on the cellular behaviour, in terms of proliferation and osteogenic differentiation.
MACROPOROUS ALGINATE FOAMS CROSSLINKED WITH STRONTIUM FOR BONE TISSUE ENGINEERING
Ovidio Catanzano;Giovanna Gomez d'Ayala;Paola Laurienzo;Mario Malinconico;Maria Grazia Raucci;
2016
Abstract
Nowadays bone defects and age related orthopedic disorders have become a critical public health issue. New tissue engineering strategies allowed the development of different technique for the de novo generation of bone tissue, including the use of autologous bone forming cells. In this case, biocompatible three-dimensional porous scaffolds materials are essential to mimic the native bone tissue microenvironment, giving a structural support and, at the same time, allow the transportation of nutrients and oxygen to the growing cells. To this purpose, this work is based on the development of new solid alginate foams with a suitable microporosity to support and enhance growth and osteogenic differentiation of human Mesenchymal Stem cells (hMSCs). Macroporous alginate foams (MAFs) were formulated by freeze-drying of hydrogels prepared by internal gelation [1] using glucono-?-lactone (GDL) and strontium carbonate. Strontium is well known as bone anabolic agent and in this case it was used with a double function: (I) cross-linking agent for the alginate chains and (II) enhancer of the osteogenic differentiation of mesenchymal stem cells (MSCs) thanks to an in situ release from the foam [2]. To obtain a macroporous uniform structure, sodium bicarbonate and pluronic F127 were added as foaming agents and foam stabilizer, respectively. The MAFs were tested for functional characteristics including mechanical strength, porous structure, stability, water content and swelling. A preliminary formulative study was carried out to define the optimal conditions to produce MAFs with different shapes and size. The acidic environment, created by the hydrolysis of GDL, promotes dissolution of strontium carbonate and development of CO2 from sodium bicarbonate, generating the physical crosslinking and the microporosity in only one step. After the freeze-drying process, MAFs were soft, flexible, elegant in appearance, non-brittle in nature and, due to their porous nature, have proved to be suitable for cell migration whilst still maintaining their physical integrity. Porosity was evaluated by scanning electron microscopy (SEM) showing interconnected pores with a well-defined size range. Furthermore, mechanical characterization demonstrated that the MAFs were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed bone tissue. In conclusion, MAFs seems to be a very promising three-dimensional scaffold for in vitro bone cell growth. Further studies are in progress to evaluate the effect of the scaffold and of Sr2+ ions released in the environment on the cellular behaviour, in terms of proliferation and osteogenic differentiation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.