СОВРЕМЕННЫЕ ПОДХОДЫ ИНЖЕНЕРИИ КОСТНОЙ ТКАНИ

This article discusses the modern approaches of bone tissue engineering in oral and maxillofacial surgery for repair of bone integrity. Describes the new biomaterials in bone tissue engineering, complex scaffolds containing MSC for bone repair of large and critical bone defects, the criteria for selecting biomaterial scaffolds, as well as their positive and negative properties.В данной обзорной статье рассматриваются современные методы тканевой инженерии костной ткани, которые применяются в хирургической стоматологии и челюстно-лицевой хирургии для восстановления обширных дефектов челюстных и других костей черепа. Представлена характеристика сложных скаффолдов, содержащих стволовые клетки, а также отражены критерии выбора каркасных материалов, их положительные и отрицательные свойства

СОВРЕМЕННЫЕ ПОДХОДЫ ИНЖЕНЕРИИ КОСТНОЙ ТКАНИ

This article discusses the modern approaches of bone tissue engineering in oral and maxillofacial surgery for repair of bone integrity. Describes the new biomaterials in bone tissue engineering, complex scaffolds containing MSC for bone repair of large and critical bone defects, the criteria for selecting biomaterial scaffolds, as well as their positive and negative properties.В данной обзорной статье рассматриваются современные методы тканевой инженерии костной ткани, которые применяются в хирургической стоматологии и челюстно-лицевой хирургии для восстановления обширных дефектов челюстных и других костей черепа. Представлена характеристика сложных скаффолдов, содержащих стволовые клетки, а также отражены критерии выбора каркасных материалов, их положительные и отрицательные свойства

РАЗРАБОТКА ТКАНЕИНЖЕНЕРНОИ ТЕРАПЕВТИЧЕСКОЙ СИСТЕМЫ НА ОСНОВЕ ГИБРИДНОИ КОНСТРУКЦИИ ИЗ ПОЛИ-3-ОК-СИБУТИРАТА С ГИДРОКСИАПАТИТОМ, ЗАПОЛНЕННОЙ АЛЬГИНАТНЫМ ГИДРОГЕЛЕМ, СОДЕРЖАЩИМ МЕЗЕНХИМАЛЬНЫЕ СТВОЛОВЫЕ КЛЕТКИ

The purpose of this study was the development of three-dimensional hybrid tissue-engineered construct based on poly-3-oxybutyrate and mesenchymal stem cells for the replacement of bone defects. Regeneration of bone defects was studied on the model of the critical bone defect of the cranial vault in rats. To restore them, three-dimensional tissue-engineered construct (TEC) were manufactured on the basis of a composite of poly-3-oxybutyrate (POB) and nanosized hydroxyapatite (HAp): with a 3D printer a mold was printed, where a scaffold was formed using a double leaching methodfrom a POB /HAp composite. On the basis of the obtained scaffold, TEC was formed by filling it with sodium alginate solution (ALG) and mesenchymal stem cells (MSC) suspended therein, followed by its gelation. After TEC was placed in a critical bone defect, the dynamics and the parameters of regeneration was studied. After one month implantation results, namely, osteogenic activity, were determined using cone-beam tomography and histomorphome-try. The conducted studies showed that the developed by us TEC has osteogenic properties and promotes the regeneration of flat bones of the rats skulls. Implantation of TEC provides closure of the critical bone defect of the cranial vault in the rat to 92% of its area during 1 month of observation, presumably due to the introduced scaffold into the design of MSCs and biomaterials, capable of stimulating bone growth. Thus, the developed tissue-engineered construct possesses osteogenic properties, potentiating the regeneration of critical bone defects of the cranium of rat skull.Целью данного исследования явилась разработка трёхмерных гибридных тканеинженерных конструкций (ТИК) на основе поли-3-оксибутирата (ПОБ) и мезенхимальных стволовых клеток (МСК) для замещения костных дефектов. Регенерацию костных дефектов изучали на модели критического костного дефекта свода черепа у крыс. Для их восстановления были изготовлены трехмерные тканеинженерные конструкции на основе композита поли-3-оксибутирата и наноразмерного гидрок-сиапатита (ГАП): при помощи 3D-принтера была напечатана пресс-форма, в которой методом двойного выщелачивания из композита ПОБ/ГАП был сформирован скаффолд. На основе полученного скаффолда сформировали ТИК, заполнив ее раствором альгината натрия (АЛГ) и суспензированными в нем мезенхимальными стволовыми клетками с последующим его гелированием. ТИК помещали в критический костный дефект и исследовали динамику, а также параметры регенерации. Результаты имплантации, а именно остеогенную активность определяли через месяц с использованием конусно-лучевой томографии и методом гистоморфометрии. Проведенные исследования показали, что разработанная нами ТИК обладает остеогенными свойствами и способствует регенерации плоских костей черепа у крыс. Имплан-тациия ТИК обеспечивает закрытие критического костного дефекта свода черепа у крысы до 92% его площади в течение 1 месяца наблюдений, по-видимому, благодаря введенным в конструкцию МСК и биоматериалам скаффолда, способным к стимуляции роста костной ткани. Таким образом, разработанная тканеинженерная конструкция обладает остеогенными свойствами, потенции-руя регенерацию критических костных дефектов свода черепа крыс

Development and preclinical studies of orthotopic bone implants based on a hybrid construction from poly(3-hydroxybutyrate) and sodium alginate

The aim of the investigation was to develop a technology of manufacturing bone implants based on a hybrid polymer construction composed of poly(3-hydroxybutyrate) and sodium alginate for guided bone regeneration using 3D printing method. Materials and Methods. Complex shaped bone implants based on poly(3-hydroxybutyrate) and sodium alginate were manufactured by the method of two-stage leaching using a mold obtained by 3D printing. The appearance, morphology and structure of the obtained scaffolds were analyzed by means of scanning electron microscopy. Biocompatibility in vivo was determined based on the histology data of scaffolds implantation as bone substitutes. Results. The study of the developed hybrid 3D scaffolds from poly(3-hydroxybutyrate) and sodium alginate showed that they perform a restrictive function providing conditions for regeneration of flat cranial bones in rats. Conclusion. The developed hybrid 3D scaffolds do not interfere with normal osteogenesis and provide beneficial conditions for regeneration. © 2016, Nizhny Novgorod State Medical Academy. All rights reserved

Development and preclinical studies of orthotopic bone implants based on a hybrid construction from poly(3-hydroxybutyrate) and sodium alginate

The aim of the investigation was to develop a technology of manufacturing bone implants based on a hybrid polymer construction composed of poly(3-hydroxybutyrate) and sodium alginate for guided bone regeneration using 3D printing method. Materials and Methods. Complex shaped bone implants based on poly(3-hydroxybutyrate) and sodium alginate were manufactured by the method of two-stage leaching using a mold obtained by 3D printing. The appearance, morphology and structure of the obtained scaffolds were analyzed by means of scanning electron microscopy. Biocompatibility in vivo was determined based on the histology data of scaffolds implantation as bone substitutes. Results. The study of the developed hybrid 3D scaffolds from poly(3-hydroxybutyrate) and sodium alginate showed that they perform a restrictive function providing conditions for regeneration of flat cranial bones in rats. Conclusion. The developed hybrid 3D scaffolds do not interfere with normal osteogenesis and provide beneficial conditions for regeneration. © 2016, Nizhny Novgorod State Medical Academy. All rights reserved

Poly(3-hydroxybutyrate)/hydroxyapatite/alginate scaffolds seeded with mesenchymal stem cells enhance the regeneration of critical-sized bone defect

A critical-sized calvarial defect in rats is employed to reveal the osteoinductive properties of biomaterials. In this study, we investigate the osteogenic efficiency of hybrid scaffolds based on composites of a biodegradable and biocompatible polymer, poly(3-hydroxybutyrate) (PHB) with hydroxyapatite (HA) filled with alginate (ALG) hydrogel containing mesenchymal stem cells (MSCs) on the regeneration of the critical-sized radial defect of the parietal bone in rats. The scaffolds based on PHB and PHB/HA with desired shapes were prepared by two-stage salt leaching technique using a mold obtained by three-dimensional printing. To obtain PHB/HA/ALG/MSC scaffolds seeded with MSCs, the scaffolds were filled with ALG hydrogel containing MSCs; acellular PHB/ALG and PHB/ALG filled with empty ALG hydrogel were prepared for comparison. The produced scaffolds have high porosity and irregular interconnected pore structure. PHB/HA scaffolds supported MSC growth and induced cell osteogenic differentiation in a regular medium in vitro that was manifested by an increase in ALP activity and expression of the CD45 phenotype marker. The data of computed tomography and histological studies showed 94% and 92%, respectively, regeneration of critical-sized calvarial bone defect in vivo at 28th day after implantation of MSC-seeded PHB/HA/ALG/MSC scaffolds with 3.6 times higher formation of the main amount of bone tissue at 22–28 days in comparison with acellular PHB/HA/ALG scaffolds that was shown at the first time by fluorescent microscopy using the original technique of intraperitoneal administration of fluorescent dyes to living postoperative rats. The obtained in vivo results can be associated with the MSC-friendly microstructure and in vitro osteogenic properties of PHB/HA base-scaffolds. Thus, the obtained data demonstrate the potential of MSCs encapsulated in the bioactive biopolymer/mineral/hydrogel scaffold to improve the bone regeneration process in critical-sized bone defects. © 2020 Elsevier B.V