Στην παρούσα διπλωματική εργασία μελετήθηκε η αποδέσμευση τριών βιοδραστικών ουσιών με διαφορετική διαλυτότητα στο νερό, από υδρόφιλες μήτρες αποτελούμενες από άλατα του φωσφορικού ασβεστίου. Οι υδρόφιλες μήτρες κυρίως πολυμερών, χρησιμοποιούνται ευρύτατα στην ελεγχόμενη αποδέσμευση βιοδραστικών ουσιών από στερεές φαρμακοτεχνικές μορφές διότι μπορούν να παρέχουν τα απαιτούμενα χαρακτηριστικά αποδέσμευσης (ρυθμός και ποσοστό αποδέσμευσης έναντι χρόνου). Σημαντικά πλεονεκτήματα των αλάτων του φωσφορικού ασβεστίου είναι το χαμηλό κόστος παραγωγής των και το γεγονός ότι πρόκειται για βιοσυμβατά και βιοδιασπώμενα υλικά. Οι βιοδραστικές ενώσεις που μελετήθηκαν ήταν η καφεϊνη, η θεοφυλλίνη και η θεοβρωμίνη που έχουν την ίδια βασική χημική δομή και ανήκουν στην κατηγορία των μεθυλοξανθινών, αλλά έχουν διαφορετική διαλυτότητα στο νερό. Οι υδρόφιλες μήτρες των αλάτων του φωσφορικού ασβεστίου που μελετήθηκαν στην παρούσα εργασία ήταν α) δισκία τα οποία παρασκευάσθηκαν με συμπίεση μιγμάτων των αλάτων του φωσφορικού ασβεστίου και της βιοδραστικής ένωσης με ορισμένη σύσταση και β) οστικά τσιμέντα τα οποία παρασκευάσθηκαν με επεξεργασία μίγματος αλάτων του φωσφορικού ασβεστίου και της βιοδραστικής ένωσης με φωσφορικό οξύ. Μελετήθηκε η μεταβολή του ρυθμού και του ποσοστού αποδέσμευσης των βιοδραστικών ουσιών έναντι του χρόνου α) για διαφορετικές συστάσεις της υδρόφιλης μήτρας, β) με την υδατοδιαλυτότητα της βιοδραστικής ένωσης, γ) με την ταχύτητα ανάδευσης του μέσου διαλυτοποίησης και δ) με την σύσταση του μέσου διαλυτοποίησης. Επίσης τα κινητικά δεδομένα (ποσοστό αποδέσμευσης έναντι του χρόνου) αναλύθηκαν με βάση ορισμένα κινητικά πρότυπα προκειμένου να προσδιορισθεί το κινητικό πρότυπο ή πρότυπα που καθορίζουν την αποδέσμευση των παραπάνω βιοδραστικών ενώσεων από τα δισκία και τα οστικά τσιμέντα αλάτων του φωσφορικού ασβεστίου. / -

Submitted by CLAUDIA VILALVA CASSARO null (claudia.v.cassaro@gmail.com) on 2018-03-21T13:51:17Z No. of bitstreams: 1 dissertacao claudia_cassaroFINAL.pdf: 3809022 bytes, checksum: a5c8891039ce6bc569b42ee66058c846 (MD5) / Rejected by Luciana Pizzani null (luciana@btu.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: Necessário fazer as seguintes correções no arquivo submetido: problema 1: Assinalar a agência de fomento (no seu caso CAPES). problema 2: No campo número do financiamento: colocar o número do processo. Assim que tiver efetuado as correções submeta o arquivo em PDF novamente. Agradecemos a compreensão. on 2018-03-22T12:35:28Z (GMT) / Submitted by CLAUDIA VILALVA CASSARO null (claudia.v.cassaro@gmail.com) on 2018-03-22T15:52:41Z No. of bitstreams: 1 dissertacao claudia_cassaroFINAL.pdf: 3809022 bytes, checksum: a5c8891039ce6bc569b42ee66058c846 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-03-23T12:00:14Z (GMT) No. of bitstreams: 1 cassaro_cv_me_bot.pdf: 3809022 bytes, checksum: a5c8891039ce6bc569b42ee66058c846 (MD5) / Made available in DSpace on 2018-03-23T12:00:14Z (GMT). No. of bitstreams: 1 cassaro_cv_me_bot.pdf: 3809022 bytes, checksum: a5c8891039ce6bc569b42ee66058c846 (MD5) Previous issue date: 2018-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O reparo do tecido ósseo é um desafio antigo da ciência mundial. A partir das décadas de 70-80, os biomateriais passaram a ser explorados e hoje desempenham importante papel na engenharia tecidual. Estes, quando aplicados na enxertia óssea, devem ser bioativos, biocompatíveis e reabsorvíveis. A integração entre os diversos materiais de origem sintética e os arcabouços biológicos possui amplo espectro de uso. Dentre os arcabouços destacam-se os compostos à base de fibrina por suas propriedades hemostáticas, estabilidade e morfologia favorável à proliferação celular. A presente revisão abordou a estrutura e constituição do tecido ósseo e suas limitações no processo de reparo, a relevância da engenharia tecidual aplicada à esta finalidade e os biomateriais utilizados para otimizar tal processo, com ênfase especial aos materiais compostos por fosfatos de cálcio, células tronco mesenquimais e sua aplicação junto ao arcabouço biológico selante de fibrina, com destaque para o selante heterólogo de fibrina, agora denominado biopolímero de fibrina, um produto único e em fase de testes em experimentação animal e estudos clínicos. Propõe-se, ao final desta, uma nova abordagem para a regeneração de defeitos ósseos de ratos baseada na associação entre o selante heterólogo de fibrina, o fosfato de cálcio bifásico e células tronco mesenquimais. / Bone tissue repair is an ancient challenge of world science. From the 70s and 80s, biomaterials began to be explored and nowadays play an important role in tissue engineering. These, when applied in bone grafting, have to be bioactive, biocompatible and resorbable. The integration between the various materials of synthetic origin and biological scaffolds has a wide spectrum of use. Among these scaffolds, fibrin-based compounds are distinguished by their hemostatic properties, stability and morphology favorable to cell proliferation. The present review addressed the structure and constitution of bone tissue and its limitations in the repair process, the relevance of tissue engineering approaches applied to this purpose and the biomaterials used to optimize this process, with special emphasis on materials composed of calcium phosphates, mesenchymal stem cells and its application with the biological sealant fibrin scaffold, highlighting the heterologous fibrin sealant, now named as fibrin biopolymer, a unique product testing in animal experimentation and clinical studies. At the end of this, a new approach is proposed for the regeneration of rat bone defects based on the association between heterologous fibrin sealant, biphasic calcium phosphate and mesenchymal stem cells.

Orientador: Benedito Barraviera / Resumo: O reparo do tecido ósseo é um desafio antigo da ciência mundial. A partir das décadas de 70-80, os biomateriais passaram a ser explorados e hoje desempenham importante papel na engenharia tecidual. Estes, quando aplicados na enxertia óssea, devem ser bioativos, biocompatíveis e reabsorvíveis. A integração entre os diversos materiais de origem sintética e os arcabouços biológicos possui amplo espectro de uso. Dentre os arcabouços destacam-se os compostos à base de fibrina por suas propriedades hemostáticas, estabilidade e morfologia favorável à proliferação celular. A presente revisão abordou a estrutura e constituição do tecido ósseo e suas limitações no processo de reparo, a relevância da engenharia tecidual aplicada à esta finalidade e os biomateriais utilizados para otimizar tal processo, com ênfase especial aos materiais compostos por fosfatos de cálcio, células tronco mesenquimais e sua aplicação junto ao arcabouço biológico selante de fibrina, com destaque para o selante heterólogo de fibrina, agora denominado biopolímero de fibrina, um produto único e em fase de testes em experimentação animal e estudos clínicos. Propõe-se, ao final desta, uma nova abordagem para a regeneração de defeitos ósseos de ratos baseada na associação entre o selante heterólogo de fibrina, o fosfato de cálcio bifásico e células tronco mesenquimais. / Abstract: Bone tissue repair is an ancient challenge of world science. From the 70s and 80s, biomaterials began to be explored and nowadays play an important role in tissue engineering. These, when applied in bone grafting, have to be bioactive, biocompatible and resorbable. The integration between the various materials of synthetic origin and biological scaffolds has a wide spectrum of use. Among these scaffolds, fibrin-based compounds are distinguished by their hemostatic properties, stability and morphology favorable to cell proliferation. The present review addressed the structure and constitution of bone tissue and its limitations in the repair process, the relevance of tissue engineering approaches applied to this purpose and the biomaterials used to optimize this process, with special emphasis on materials composed of calcium phosphates, mesenchymal stem cells and its application with the biological sealant fibrin scaffold, highlighting the heterologous fibrin sealant, now named as fibrin biopolymer, a unique product testing in animal experimentation and clinical studies. At the end of this, a new approach is proposed for the regeneration of rat bone defects based on the association between heterologous fibrin sealant, biphasic calcium phosphate and mesenchymal stem cells. / Mestre