Новые методы поверхностного и объемного модифицирования материалов на основе биоразлагаемых полиэфиров для медицинских применений

Введение …………………………………………………………………………………………………………… 6
Глава 1 Литературный обзор ……………………………………………………………………………. 12
1.1 Использование скаффолдов на основе биоразлагаемых полимеров в
медицине …………………………………………………………………………………………………. 12
1.1.1 Биоразлагаемые волокнистые скаффолды для целевой доставки
лекарственных средств …………………………………………………………………………. 12

1.1.2 Биоразлагаемые волокнистые скаффолды в регенеративной
медицине ……………………………………………………………………………………………… 13

1.2 Поли(ε-капролактон) и поли(молочная кислота)………………………………….. 14
1.3 Методы формования скаффолдов на основе биоразлагаемых
полиэфиров ……………………………………………………………………………………………… 17
1.3.1 Электроформование ……………………………………………………………………… 17

1.3.2 Формование под действием центробежной силы …………………………… 17

1.3.3 Аэродинамическое формование ……………………………………………………. 18

1.3.4 Фазовое разделение ……………………………………………………………………… 18

1.3.5 Прядильная технология с контролируемыми параметрами ……………. 18

1.3.6 Методы модифицирования скаффолдов на основе биоразлагаемых
полиэфиров ………………………………………………………………………………………….. 20

1.3.7 Методы поверхностного модифицирования ………………………………….. 20

1.3.8 Методы модифицирования в объеме …………………………………………….. 23

Глава 2 Экспериментальная часть ……………………………………………………………………. 25
Глава 3. Поверхностное модифицирование с использованием обработки смесью
хорошего и плохого растворителей ………………………………………………………………….. 35
3.1 Поверхностное модифицирование пленок из поли(молочной кислоты) .. 35
3.1.1 Выбор системы «хороший/плохой растворитель» …………………………. 36

3.1.2 Подбор условий проведения модифицирования ……………………………. 36
3.1.3 Качественная и количественная оценка результатов
модифицирования пленок из поли(молочной кислоты) …………………………. 39

3.2 Получение скаффолдов на основе поли(ε-капролактона) и поли(молочной
кислоты), содержащих иод на поверхности волокон, с использованием
метода «хороший/плохой растворитель» ………………………………………………….. 47
3.2.1 Подбор состава системы «хороший/плохой растворитель» ……………. 48

3.2.2 Изучение динамики нанесения иода на поверхность волокон ……….. 53

3.3 Физико-химические свойства скаффолдов, содержащих иод на
поверхности волокон ……………………………………………………………………………….. 54
3.3.1 Морфология скаффолдов, содержащих иод на поверхности волокон 54

3.3.2 Механические свойства скаффолдов, содержащих иод на поверхности
волокон ………………………………………………………………………………………………… 57

3.4 Антибактериальные свойства скаффолдов, содержащих иод на
поверхности волокон ……………………………………………………………………………….. 57
3.5 Получение скаффолдов на основе поли(молочной кислоты), содержащих
желатин на поверхности волокон, с использованием метода
«хороший/плохой растворитель» ……………………………………………………………… 60
3.6 Физико-химические свойства скаффолдов, содержащих желатин на
поверхности волокон ……………………………………………………………………………….. 62
3.6.1 Морфология скаффолдов, содержащих желатин на поверхности
волокон ………………………………………………………………………………………………… 62

3.6.2 Гидрофильность скаффолдов, содержащих желатин на поверхности
волокон ………………………………………………………………………………………………… 64

3.6.3 Механические свойства скаффолдов, содержащих желатин на
поверхности волокон ……………………………………………………………………………. 64

3.7 Исследование биосовместимости скаффолдов, содержащих желатин на
поверхности волокон ……………………………………………………………………………….. 65
3.8 Краткие выводы по главе 3 …………………………………………………………………. 66
Глава 4. Получение композитных материалов, модифицированных в объеме …… 68
4.1 Получение скаффолдов на основе поли(ε-капролактона), содержащих L-
аргинин ……………………………………………………………………………………………………. 68
4.2 Физико-химические свойства скаффолдов, содержащих L-аргинин …….. 69
4.2.1 Изучение влияния концентрации L-аргинина в прядильном растворе
на морфологию полученных скаффолдов ……………………………………………… 69

4.2.2 Механические свойства скаффолдов с различным содержанием L-
аргинина ………………………………………………………………………………………………. 70

4.3 Исследование биосовместимости скаффолдов, содержащих L-аргинин, in
vitro …………………………………………………………………………………………………………. 71
4.4 Получение скаффолдов на основе поли(ε-капролактона) и
поливинилпирролидона с использованием гексафторизопропанола в качестве
общего растворителя………………………………………………………………………………… 72
4.4.1 Изучение влияния соотношения поли(ε-капролактона) и
поливинилпирролидона в прядильном растворе на морфологию
полученных материалов ……………………………………………………………………….. 75

4.5 Физико-химические свойства скаффолдов на основе поли(ε-
капролактона) и поливинилпирролидона ………………………………………………….. 76
4.5.1 Механические свойства скаффолдов с различным соотношением
поли(ε-капролактона) и поливинилпирролидона …………………………………… 76

4.5.2 Изучение стабильности полученных материалов в водной среде …… 78

4.6 Исследование биосовместимости скаффолдов на основе поли(ε-
капролактона) и поливинилпирролидона ………………………………………………….. 81
4.6.1 Клеточные исследования in vitro …………………………………………………… 81

4.6.2 Краткие выводы по главе 4 …………………………………………………………… 82

ОСНОВНЫЕ ВЫВОДЫ ………………………………………………………………………………….. 84
Список литературы …………………………………………………………………………………………. 85
Приложение А Акт об использовании результатов диссертационной работы …… 97
Приложение Б Акт внедрения в научную деятельность результатов
диссертационной работы …………………………………………………………………………………. 99
Приложение В Акт внедрения в научную деятельность результатов
диссертационной работы ……………………………………………………………………………….. 100
Приложение Г Акт внедрения в учебном процессе результатов диссертационной
работы …………………………………………………………………………………………………………… 101
Приложение Д Патент на изобретение …………………………………………………………… 102

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