We, as human beings, are explorers at the speed of our thoughts, of our imagination, of our feet, and of our eyes. Nowadays, humans aim at reaching Mars, contemplating the possibility of becoming a two-planet species. Nonetheless, there are physiological problems that must be addressed and overcome since “Miss Evolution” has selected us to be functional on the planet Earth. Spaceflights place the human body into a vast sparkling void rich of health hazards. Indeed, foreseeing, studying and countermeasuring how the body copes with long-duration spaceflight is of the utmost importance for a successful mission. Every system is involved and in astronauts’ bodies it has actually been seen how those significant adaptations undergo, while thier physical structure tries to find a new equilibrium in an unusual environment. In line with Wolff’s Law, the removal of gravitational loading leads concomitantly to a decrease in bone formation and an increase in bone resorption, thereby dysregulating the bone remodeling process. Data obtained from past six-months missions highlighted a loss of up to 2-3% of weight-bearing bone mass per month. Mathematical models predicted that all crew members participating in a Mars mission would meet the WHO criteria for osteopenia, with a part meeting the criteria for osteoporosis. Evidences showed that strontium-substituted hydroxyapatite nanoparticles (SrHA-NPs) exert a dual action both on osteoblasts and osteoclasts, enhancing bone matrix deposition while reducing osteoclasts differentiation. The enrichment of collagen sponges with strontium hydroxyapatite can constitute a crucial point in bone remodeling modulation, merging together the properties of osseointegration, osteoinduction and osteoconduction. The unique innovative nanosystem described and analyzed in this thesis showed compelling results when applied in an in vitro setup involving different bone cells. Studies have been conducted on bone cells subjected to µg and this system proved its efficacy in counteracting µg-driven impairments of cells differentiation and activity, possibly avoiding common complications related to pharmacological treatments. Indeed, future standardized fracture and unloading mouse models are crucial to shed light on the molecular processes of bone regeneration and consequently develop new therapeutic interventions. Further studies are needed, however the key to therapeutically resolve conditions and pathologies involving BR dysregulation is thought to resides in learning how to enhance and modulate the intrinsic “force of Nature” (i.e. bone remodeling) of human bones. In that, up to now our system has provided evidence of heading toward the right direction.
OLTRE LA MEDICINA SPAZIALE: valutazione in vitro ed in vivo di nanoparticelle di idrossiapatite arricchite con Sr come contromisura per l'osteoporosi indotta da microgravità.
TO SPACE MEDICINE AND BEYOND: in vitro and in vivo evaluation of Sr-hydroxyapatite nanoparticles as countermeasure to microgravity-induced osteoporosis
PREDA, EMMA MARIA
2019/2020
Abstract
We, as human beings, are explorers at the speed of our thoughts, of our imagination, of our feet, and of our eyes. Nowadays, humans aim at reaching Mars, contemplating the possibility of becoming a two-planet species. Nonetheless, there are physiological problems that must be addressed and overcome since “Miss Evolution” has selected us to be functional on the planet Earth. Spaceflights place the human body into a vast sparkling void rich of health hazards. Indeed, foreseeing, studying and countermeasuring how the body copes with long-duration spaceflight is of the utmost importance for a successful mission. Every system is involved and in astronauts’ bodies it has actually been seen how those significant adaptations undergo, while thier physical structure tries to find a new equilibrium in an unusual environment. In line with Wolff’s Law, the removal of gravitational loading leads concomitantly to a decrease in bone formation and an increase in bone resorption, thereby dysregulating the bone remodeling process. Data obtained from past six-months missions highlighted a loss of up to 2-3% of weight-bearing bone mass per month. Mathematical models predicted that all crew members participating in a Mars mission would meet the WHO criteria for osteopenia, with a part meeting the criteria for osteoporosis. Evidences showed that strontium-substituted hydroxyapatite nanoparticles (SrHA-NPs) exert a dual action both on osteoblasts and osteoclasts, enhancing bone matrix deposition while reducing osteoclasts differentiation. The enrichment of collagen sponges with strontium hydroxyapatite can constitute a crucial point in bone remodeling modulation, merging together the properties of osseointegration, osteoinduction and osteoconduction. The unique innovative nanosystem described and analyzed in this thesis showed compelling results when applied in an in vitro setup involving different bone cells. Studies have been conducted on bone cells subjected to µg and this system proved its efficacy in counteracting µg-driven impairments of cells differentiation and activity, possibly avoiding common complications related to pharmacological treatments. Indeed, future standardized fracture and unloading mouse models are crucial to shed light on the molecular processes of bone regeneration and consequently develop new therapeutic interventions. Further studies are needed, however the key to therapeutically resolve conditions and pathologies involving BR dysregulation is thought to resides in learning how to enhance and modulate the intrinsic “force of Nature” (i.e. bone remodeling) of human bones. In that, up to now our system has provided evidence of heading toward the right direction.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12043