Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Despite current treatment options such as combined chemotherapy and surgical resection, the survival rate remains notably low due to the tumor's infiltrative growth and susceptibility to metastasis. Boron Neutron Capture Therapy (BNCT), an experimental binary radiotherapy, could be considered as an alternative or integrative treatment to conventional therapies. BNCT involves irradiating neoplastic cells enriched with a stable non- radioactive isotope of boron (10B) with epithermal neutrons. The subsequent neutron capture reaction in boron releases two ionizing particles that dissipate all their energy within a distance comparable to the diameter of a cell, causing irreparable DNA damage and providing a way to selectively destroy cancer cells while sparing surrounding normal cells. Therefore, it is particularly suitable for the treatment of widespread or invasive tumors. The innovative approach adopted in this study includes the use of 3D bioprinting to create three-dimensional models of osteosarcoma for testing the effects of BNCT. 3D bioprinting, through the layer-by-layer deposition of biomaterials and cells, has allowed the creation of constructs that better replicate the complexity of solid tumors compared to traditional 2D models. This approach aligns with the principles of the 3Rs in animal experimentation, reducing the need for animal models. The research focused on optimizing the printing protocol, examining biomaterial selection, cell density, and the crosslinking process. The goal was to enhance cell colonization in the constructs and subsequently assess the applicability of BNCT through targeted experiments. Challenges related to quantifying intracellular boron were addressed due to interference of the gel matrix used in the printing process. Various solutions were explored, including increasing the concentration of the boronated vectors and optimizing the analyses reducing the thickness of the construct realizing cryostatic-section. Preliminary results are encouraging, suggesting that the strategies employed can make osteosarcoma models suitable for experimental BNCT applications.
L’osteosarcoma è il tumore primitivo maligno dell'osso più comune nei bambini e negli adolescenti. Nonostante le opzioni di trattamento attuali, quali chemioterapia combinata e resezione chirurgica, il tasso di sopravvivenza rimane notevolmente basso a causa della crescita infiltrativa del tumore e della suscettibilità alle metastasi. Per questo motivo, la Terapia per Cattura Neutronica del Boro (BNCT), una radioterapia binaria sperimentale, è stata studiata come trattamento alternativo o integrativo ai trattamenti convenzionali. La BNCT si basa sull’irraggiamento con neutroni termici di cellule neoplastiche precedentemente arricchite con un isotopo stabile non radioattivo del boro (10B). La successiva reazione di cattura dei neutroni nel boro rilascia due particelle ionizzanti che dissipano tutta la loro energia in una distanza paragonabile al diametro di una cellula, causando danni non riparabili al DNA e fornendo così un modo per distruggere selettivamente le cellule cancerose risparmiando le cellule normali circostanti. Pertanto, è particolarmente indicata nel trattamento di tumori diffusi o infiltranti. L'approccio innovativo adottato in questo studio include l'utilizzo del 3D bioprinting per creare costrutti tridimensionali di osteosarcoma impiegabili come modello alternativo, per studi inerenti la BNCT. La tecnica del 3D bioprinting, mediante la deposizione strato su strato di biomateriali e cellule, ha permesso la realizzazione di costrutti che meglio replicano la complessità dei tumori solidi rispetto ai tradizionali modelli 2D. Questo approccio risponde ai principi delle 3R nella sperimentazione animale, riducendo la necessità di utilizzare modelli animali. Il lavoro di ricerca si è concentrato sull'ottimizzazione del protocollo di stampa, esaminando la scelta dei biomateriali, la densità cellulare e il processo di crosslinking. L'obiettivo è stato migliorare la colonizzazione cellulare nei costrutti, successivamente valutare l’applicabilità della BNCT attraverso esperimenti mirati. Sono stati affrontati ostacoli legati alla quantificazione del boro intracellulare dovuti all'interferenza della matrice dei gel utilizzati nel processo di stampa. Sono state esplorate diverse soluzioni, tra cui l'incremento della concentrazione del vettore borato e l'ottimizzazione delle analisi effettuate su più sottili sezioni criostatiche anziché sull’intero costrutto. I risultati preliminari sono incoraggianti, dimostrando che le strategie adottate possono rendere i modelli di osteosarcoma idonei per gli studi sperimentali in ambito BNCT.
3D BIOPRINTED OSTEOSARCOMA CONSTRUCTS: AN ALTERNATIVE MODEL FOR BORON NEUTRON CAPTURE THERAPY (BNCT) STUDIES
DELGROSSO, ELENA
2024-04-19
Abstract
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Despite current treatment options such as combined chemotherapy and surgical resection, the survival rate remains notably low due to the tumor's infiltrative growth and susceptibility to metastasis. Boron Neutron Capture Therapy (BNCT), an experimental binary radiotherapy, could be considered as an alternative or integrative treatment to conventional therapies. BNCT involves irradiating neoplastic cells enriched with a stable non- radioactive isotope of boron (10B) with epithermal neutrons. The subsequent neutron capture reaction in boron releases two ionizing particles that dissipate all their energy within a distance comparable to the diameter of a cell, causing irreparable DNA damage and providing a way to selectively destroy cancer cells while sparing surrounding normal cells. Therefore, it is particularly suitable for the treatment of widespread or invasive tumors. The innovative approach adopted in this study includes the use of 3D bioprinting to create three-dimensional models of osteosarcoma for testing the effects of BNCT. 3D bioprinting, through the layer-by-layer deposition of biomaterials and cells, has allowed the creation of constructs that better replicate the complexity of solid tumors compared to traditional 2D models. This approach aligns with the principles of the 3Rs in animal experimentation, reducing the need for animal models. The research focused on optimizing the printing protocol, examining biomaterial selection, cell density, and the crosslinking process. The goal was to enhance cell colonization in the constructs and subsequently assess the applicability of BNCT through targeted experiments. Challenges related to quantifying intracellular boron were addressed due to interference of the gel matrix used in the printing process. Various solutions were explored, including increasing the concentration of the boronated vectors and optimizing the analyses reducing the thickness of the construct realizing cryostatic-section. Preliminary results are encouraging, suggesting that the strategies employed can make osteosarcoma models suitable for experimental BNCT applications.File | Dimensione | Formato | |
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Descrizione: 3D BIOPRINTED OSTEOSARCOMA CONSTRUCTS: AN ALTERNATIVE MODEL FOR BORON NEUTRON CAPTURE THERAPY (BNCT) STUDIES
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