生物材料在再生医学和组织工程中的应用-概念与展望

S. Najman, S. Stojanović, J. Živković, J. Najdanović, M. Radenković, P. Vasiljević, Nenad L. Ignjatović
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引用次数: 0

摘要

再生医学(RM)利用人体的先天潜能,借助各种生物材料有效地修复和再生受损的组织和器官。组织工程(TE)使得用新的组织和器官替换受损的组织和器官成为可能。生物材料领域的研究显著提高了RM和TE的领域。生物材料被用于骨科、牙科、心血管植入物、医疗器械、重建和再生医学等领域。生物材料用于植入的重要前提是其生物相容性和生物功能。生物材料应能使细胞粘附、迁移、增殖和分化。生物材料的生物学性质是其物理化学性质的反映,如内部结构、表面特征和电荷。用于组织再生的生物材料应模仿细胞外基质的自然结构,并代表正常细胞功能的生理微环境。这些生物材料还应具有足够的生物降解性,以促进新组织的形成和生长。用于RM的生物材料可以是天然的或合成的,聚合物的结构性质,陶瓷和复合类型,基于生物反应性,它们可以是生物惰性的或生物活性的。在RM和TE中,使用了不同类别的聚合物,天然的和合成的,可以制成智能材料。水凝胶的多孔网络结构为细胞活性提供了良好的基质。基于羟基磷灰石(HAp)的陶瓷生物材料被选择用于RM和TE,特别是固体组织。性能,如组成、粒度、材料形状、孔隙率、表面电荷、形貌等,都与HAp材料的正确使用有关。HAp的性质允许其结构、表面、微纳米级粒度设计、与聚合物、金属等的杂交,这对其应用非常重要。所设计的微纳杂化HAp结构最接近骨骼结构,使细胞环境最接近自然。骨组织工程(Bone tissue engineering, BTE)是基于细胞、骨刺激(骨诱导)因子和生物材料作为骨再生和骨缺损修复的支架和载体的组合使用。在BTE中,脂肪来源的间充质干细胞(ADSCs)通常被用于体外诱导成成骨细胞或内皮细胞,新鲜分离的基质血管部分也可以被使用。血液成分(PRP,血浆或血凝块)可以作为骨诱导因子的来源包括在BTE结构的组成中。采用体外模型和方法研究生物材料的生物相容性、免疫调节和再生潜能及其对细胞功能的影响。在体外方法之后,在临床研究之前,使用各种体内动物模型来检测生物材料的再生潜力,例如皮下植入和实验动物(小鼠,大鼠,兔)胫骨,股骨和颅骨的骨缺损。
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APPLICATIONS OF BIOMATERIALS IN REGENERATIVE MEDICINE AND TISSUE ENGINEERING – CONCEPTS AND PERSPECTIVE
Regenerative medicine (RM) exploits the innate potential of the human body to effectively repair and regenerate damaged tissues and organs with the help of various biomaterials. Tissue engineering (TE) makes it possible to replace damaged tissues and organs with new ones. Research in the field of biomaterials has significantly improved the area of RM and TE. Biomaterials are used as orthopedic, dental, cardiovascular implants, medical devices, in the fields of reconstructive and regenerative medicine, among others. Important preconditions for the biomaterial to be used for implantation are its biocompatibility and biofunctionality. Biomaterials should enable adhesion, migration, proliferation and differentiation of cells. The biological properties of biomaterials are a reflection of their physicochemical properties, such as internal architecture, surface characteristics and charge. Biomaterials used in tissue regeneration should mimic the natural structure of the extracellular matrix and represent a physiological microenvironment for normal cellular functions. These biomaterials should also have adequate biodegradability properties to facilitate the formation and growth of new tissue. Biomaterials for use in RM can be of natural or synthetic origin, polymers by structural properties, ceramic and composite type, and based on bioreactivity they can be bioinert or bioactive. In RM and TE, polymers of different classes, natural and synthetic, are used, which can be made as intelligent materials. The structure of hydrogels in the form of a porous network represents a good matrix for cell activity. Ceramic biomaterials based on hydroxyapatite (HAp) are selected for use in RM and TE, especially solid tissues. Properties, such as composition, particle size, material shape, porosity, surface charge, topography, etc., are relevant for the proper use of HAp materials. The properties of HAp allow modification of its structure, surface, particle size design at the micro and nano level, hybridization with polymers, metals, etc. which is very important for its applications. Designed micro-nanohybrid HAp structure is most similar to the bone structure, making the cell environment closest to natural. Bone tissue engineering (BTE) is based on the combined use of cells, osteostimulating (osteoinductive) factors and biomaterials as a scaffolds and carriers for bone regeneration and defects repair. In BTE adipose-derived mesenchymal stem cells (ADSCs) are often used that are induced in vitro towards osteogenic cells or endothelial cells, and freshly isolated stromal vascular fraction can also be used. Blood components (PRP, blood plasma or blood clot) can be included in the composition of the BTE construct as a source of osteoinductive factors. In vitro models and methods were used to examine the biocompatibility, immunomodulatory and regenerative potential of biomaterials, as well as their influence on cellular functions. After in vitro methods, and before clinical studies, various in vivo animal models are used to examine the regenerative potential of biomaterials, such as subcutaneous implantations and bone defects in tibia, femur and calvaria in experimental animals (mouse, rat, rabbit).
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