骨组织工程应用可降解聚合物的可能性探讨

成骨细胞细胞外基质材料的选择是骨组织工程研究中一项重要而紧迫的任务。本文阐述了理想骨组织工程基质材料的研制要求 ,介绍了几种可降解聚合物在骨组织工程中的应用现状 ,并重点介绍了 PL A、PGA及其共聚物的优缺点和相应的改进方法。作者认为 ,以合成可降解聚合物为主要组成成分的新型基质材料必将在未来骨组织工程研究中展示出可喜的应用前景     

基于有限元的骨组织工程支架结构力学性能优化分析

目的 分析骨组织工程支架微孔参数对支架力学性能的影响,为支架微孔结构的优化设计提供参考依据。方法 利用ANYSY软件建立支架微孔结构有限元模型,计算最大等效应力、最大总变形与孔隙率的关系,并分析比较不同孔径、孔间距结构对支架最大等效应力、最大总变形、内部应变的影响。结果 x、y轴方向孔间距的影响规律一致,随着孔间距从0.6 mm增加到2.0 mm,最大等效应力从63.1 MPa减小到46.3 MPa,最大总变形从23.8 μm减小到21.8 μm,最佳应变比从80%增大到84%;但随着z轴方向孔间距的增大,最大等效应力从38.3 MPa增大到47.8 MPa,最大总变形从20.8 μm增大到22.8 μm,最佳应变比在82%~85%波动。x,y轴方向孔径从0.1 mm增加到1.0 mm时,最大等效应力从32.4 MPa增大到78.4 MPa,最大总变形从19.9 μm增大到38.2 μm,最佳应变比从90%减小到53%;z轴方向孔径的增大会引起支架的最大等效应力从58.8 MPa减小到37.9 MPa,而最大总变形从23.3 μm增大到25.9 μm,最佳应变比从82%增大到87%。结论 支架孔隙率和最佳应变比越大,最大等效应力、最大总变形越小,支架生物性能和力学性能越好。研究结果对支架的结构设计和优化具有参考价值。     

静电纺聚合物纳米纤维在骨组织工程研究中的进展

组织工程骨在骨缺损、骨不连及骨折延期愈合等骨骼疾病的治疗中有重要应用前景,、组织工程支架是组织工程研究的核心内容之一,静电纺丝制备的纳米纤维以其优异的性能,近年来已开始成为骨组织支架材料的重要研究对象。综述了静电纺聚合物纳米材料包括天然高分子聚合物、人工合成聚合物及复合聚合物纺丝纤维在骨组织工程研究中的进展,提出复合聚合物电纺纤维及其改性是今后骨组织工程支架材料研究的重要方向之一;并探讨了其研究中存在的问题与应用前景。     

3D打印骨组织工程支架的制备技术

近年来,随着3D打印技术的飞速发展,人们开始通过3D打印技术去不断完善适合不同需求的定制骨组织工程支架。由于组织工程制造的支架是需要植入生物体内的,这就对支架有着极为严苛的要求。3D打印技术作为一种新兴制备骨组织工程支架的技术,其最大的优点是可以依照需求来定制个性化形状、结构,良好的宏微观结构、润湿性、机械强度和细胞反应的新型骨组织工程支架。本文回顾了2014―2019年间对骨组织工程支架的研究,对3D打印骨组织工程支架进行了总结,并且介绍了在多功能骨组织工程支架设计与制作中的理念与研究。     

胶原水凝胶在软骨与骨组织工程中的研究进展

胶原水凝胶因其具有优良的生物相容性、生物力学性能，在软骨与骨组织工程、生物填充材料、创伤修复、药物缓释和细胞培养等医学领域获得广泛的关注和应用。本文重点介绍了胶原水凝胶在软骨与骨组织工程方面的研究进展，详细阐述了胶原水凝胶的性能、交联方法和类型，并对胶原水凝胶在软骨与骨组织工程中的研究现状进行了讨论，对其应用前景进行了展望。     

脂肪干细胞在骨组织工程中的研究进展

各种原因导致的骨损伤甚至骨缺损会给患者带来较大的经济及社会负担,而骨组织工程研究能为治疗骨损伤提供新的方向。脂肪干细胞因其来源广泛、易于获取等特性在骨组织工程中发挥着重要作用,且脂肪干细胞在生长因子、机械刺激、各种信号通路的适宜刺激下能进行自我增殖并成骨分化,形成骨组织以治疗骨损伤及骨缺损,改善骨损伤带来的一系列症状。     

骨组织工程化构建中细胞三维培养力学微环境的研究

骨重建和骨塑建的力学响应机制表明力学因素在骨的组织工程化构建中起着十分重要的作用。外部力学载荷导致骨组织内部的力学微环境发生变化进而在细胞的增殖、迁移、细胞外基质的合成、细胞因子及激素分泌能力以及骨髓间充质干细胞的分化方向等方面产生重要的影响。因此,在组织工程构建过程中,细胞三维培养的力学微环境是有待深入研究的重要内容。尤其近年来引入了三维有限元分析的方法以及非侵入性高分辨率的Micro-CT影像技术,使在细观层次上进一步探索培养物内部的微观力学条件成为可能。综述了骨组织工程化构建中细胞三维培养的微环境、力学生物学效应、力学因素的施加和量化等方面的研究进展。     

可注射型组织工程骨支架材料的研究进展

可注射型组织工程骨支架材料是一种具有一定形态和机械强度的支架材料,可与种子细胞复合,以流体的形式注射到骨组织缺损部位,最终形成新骨,达到结构恢复和功能重建的目的.此材料具有创伤小、可塑性好的特点,可以修复形态不规则的骨缺损,能够很好地复合生长因子,是目前较为理想的骨组织缺损的修复方式.在众多可注射骨组织工程材料中,生物陶瓷材料、高分子材料等被证明有高度的生物相容性和良好的机械性能,已成为骨组织工程材料方面的研究重点.旨在对生物陶瓷材料、高分子材料、生物陶瓷与高分子复合材料的发展与应用作一综述.     

三维打印技术在骨组织工程领域的应用研究进展

综述了三维(3D)打印技术的出现、分类与优势等.介绍了该技术在骨组织工程领域的应用,包括光固化立体印刷、熔融沉积成型、选择性激光烧结和3D喷印的工作原理、存在的优缺点以及国内外学者在该领域的研究进展.目前骨组织工程支架的制备大多应用了3D打印技术,以生物可降解的活性材料为原料制备而成.在我国该领域虽然发展迅速,利用3D打印技术进行人工骨合成、骨科术前模拟等已经越来越普遍,亦取得了令人满意的效果,但要研发出合适的生物材料以及设备精度的改进仍是亟待解决的问题.目前,仿生器官的功能化已成为3D打印技术领域的一大困难,其中多细胞共培养、血管化及支架的制备是实现功能化必须克服的问题,相信通过努力,该项技术将会为器官的再生与修复带来更多令人瞩目的成果.     

针对组织工程多孔生物陶瓷的组织学技术优化探讨

目的 改进硬组织切片技术以适应生物陶瓷材料在骨组织工程中的研究.方法 探索硬组织切片的厚度、漂片温度、裱片方法、烤片温度和时间的最佳组合,针对阳离子防脱载玻片的使用条件进行反复比较,通过改进操作流程中的关键技术和需避免的问题,摸索出阳离子载玻片在硬组织切片裱片中的最佳应用条件,克服了硬组织切片制作技术中标本易破碎、切片易脱落及染色时染料容易吸附的缺点.结果 通过技术探索与改进,生物陶瓷支架材料体内植入后的类骨修复体标本的硬组织切片能保持其杂化后的组织结构与比较完整的材料结构,可进行Masson三色染色、苏木精-伊红(HE)及甲苯胺蓝染色.染色后镜下观察显示支架内杂化生长的组织结构完整、细胞形态清晰、切片质量好、生物陶瓷支架脱片少.荧光显微镜可观察到类骨修复体钙沉积现象完整.结论 改善了传统硬组织切片技术处理生物陶瓷材料时易于破坏组织-材料结构的缺点.改进的硬组织切片技术适应生物陶瓷材料在骨组织工程领域研究.     

New synthetic biodegradable polymers as BMP carriers for bone tissue engineering

Bone morphogenetic proteins (BMPs) are biologically active molecules capable of inducing new bone formation and are expected to be used clinically in combination with biomaterials such as bone-graft substitutes to promote bone repair. The carrier materials for BMPs have to not only secure the BMPs in the local area and diffuse them afterwards, but also to provide scaffolding for the newly formed bone. Since synthetic, biodegradable polymers with optimal properties are considered most desirable, we synthesized polylactic acid and its derivatives. Some of these were found to consistently induce ectopic bone formation when combined with BMP and implanted into the muscles of experimental animals. It was also found that the three-dimensional configuration of BMP-induced bone mass could be controlled. This means that our attempt to construct synthetic biomaterials which can induce controllable bone formation was successful.     

壳聚糖-脱细胞真皮三维材料作为骨组织工程支架材料的研究

目的观察MC3T3-El成骨前体细胞在壳聚糖-脱细胞真皮三维支架材料上的黏附情况,并评价其细胞相容性。方法通过冷冻干燥制备壳聚糖-脱细胞真皮三维支架材料,并测试其孔隙率、密度和吸水率,通过扫描电镜分析支架的微观形貌。采用体外培养细胞的方法,将MC3T3-E1细胞直接接种到壳聚糖-脱细胞真皮三维支架材料上,培养2,3,4,5h,各时间点各取3个样品,测定细胞在支架上的黏附率,确定最佳的细胞贴壁时间。将细胞接种到支架上,共培养1,3,5,7,9,11,13d,采用MTS方法绘制细胞增殖曲线,组织化学染色观察细胞形态,并利用材料试验机测试不同时间材料细胞复合物的压缩弹性模量。结果壳聚糖-脱细胞真皮材料具有连通的多孔结构,孔隙率为92.8%,密度为97.96g/L,吸水率为(2169±100)%。细胞相容性实验显示,成骨细胞易于在支架材料上黏附、增殖。结论壳聚糖-脱细胞真皮材料具有连通的孔隙,孔径较均匀,MC3T3-El成骨前体细胞易在壳聚糖-脱细胞真皮三维支架材料上黏附、增殖,表明该支架材料具有良好的细胞相容性。     

可降解生物材料聚乳酸/磷酸钙陶瓷在骨组织工程中的应用

聚乳酸和磷酸钙陶瓷都是骨组织工程中常用的可降解生物材料。前者是人工合成的多聚物,在体内降解时间较长,可起到临时支架的作用,不同结构的聚乳酸又有不同的生物特性;后者生物活性好,亲和性高,但是脆性大,抗折强度低。两者的复合物在一定程度上弥补了各自的不足,能成为新型的骨组织工程支架材料。     

The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application

Mesenchymal stem cells (MSCs) have become one of the most promising cell sources for bone tissue engineering (BTE) applications. In this review, we first highlight recent progress in the understanding of MSC biology, their in vivo niche, multi-faceted contribution to fracture healing and bone re-modelling, and their role in BTE. A literature review from clinicaltrials.gov and Pubmed on clinical usage of MSC for both orthopedic and non-orthopedic indications suggests that translational use of MSC for BTE indications is likely to bear fruit in the ensuing decade. Last, we disscuss the profound influence of ontological and antomical origins of MSC on their proliferation and osteogenesis and demonstrated human fetal MSC (hfMSC) as a superior cellular candidate for off-the-shelf BTE applications. This relates to their superior proliferation capacity, more robust osteogenic potential and lower immunogenecity, as compared to MSC from perinatal and postnatal sources. Furthermore, we discuss our experience in developing a hfMSC based BTE strategy with the integrated use of bioreactor-based dynamic priming within macroporous scaffolds, now ready for evaluation in clinical trials. In conclusion, hfMSC is likely the most promising cell source for allogeneic based BTE application, with proven advantages compared to other MSC based ones.     

生物陶瓷与骨组织工程

为修复创伤及病理因素导致的骨缺损 ,骨组织工程是一项迅速发展、不断革新的课题。本文重点综述了国外就生物陶瓷的材料学及其作为骨组织工程细胞支架方面的研究。在分子水平对生物陶瓷理化性质、生物功能以及与细胞间相互作用的认识 ,势必加深对生物陶瓷本身及骨组织工程技术的理解。     

Paper-based bioactive scaffolds for stem cell-mediated bone tissue engineering

Bioactive, functional scaffolds are required to improve the regenerative potential of stem cells for tissue reconstruction and functional recovery of damaged tissues. Here, we report a paper-based bioactive scaffold platform for stem cell culture and transplantation for bone reconstruction. The paper scaffolds are surface-engineered by an initiated chemical vapor deposition process for serial coating of a water-repellent and cell-adhesive polymer film, which ensures the long-term stability in cell culture medium and induces efficient cell attachment. The prepared paper scaffolds are compatible with general stem cell culture and manipulation techniques. An optimal paper type is found to provide structural, physical, and mechanical cues to enhance the osteogenic differentiation of human adipose-derived stem cells (hADSCs). A bioactive paper scaffold significantly enhances in vivo bone regeneration of hADSCs in a critical-sized calvarial bone defect. Stacking the paper scaffolds with osteogenically differentiated hADSCs and human endothelial cells resulted in vascularized bone formation in vivo. Our study suggests that paper possesses great potential as a bioactive, functional, and cost-effective scaffold platform for stem cell-mediated bone tissue engineering. To the best of our knowledge, this is the first study reporting the feasibility of a paper material for stem cell application to repair tissue defects.     

Optimization of scaffold design for bone tissue engineering: A computational and experimental study

In bone tissue engineering, the scaffold has not only to allow the diffusion of cells, nutrients and oxygen but also provide adequate mechanical support. One way to ensure the scaffold has the right properties is to use computational tools to design such a scaffold coupled with additive manufacturing to build the scaffolds to the resulting optimized design specifications. In this study a topology optimization algorithm is proposed as a technique to design scaffolds that meet specific requirements for mass transport and mechanical load bearing. Several micro-structures obtained computationally are presented. Designed scaffolds were then built using selective laser sintering and the actual features of the fabricated scaffolds were measured and compared to the designed values. It was possible to obtain scaffolds with an internal geometry that reasonably matched the computational design (within 14% of porosity target, 40% for strut size and 55% for throat size in the building direction and 15% for strut size and 17% for throat size perpendicular to the building direction). These results support the use of these kind of computational algorithms to design optimized scaffolds with specific target properties and confirm the value of these techniques for bone tissue engineering.     

纳米骨组织工程支架材料生物学效应研究进展

国内外学者将纳米技术运用于支架材料制备了一系列新型的骨组织工程支架材料,并对纳米生物学效应进行了深入的研究。纳米生物材料的生物学效应研究可以更好地从分子水平上认识材料与生命体的相互作用,为构建具有生理功能的新型生物材料提供研究思路和方向。为了更好地认识纳米材料对蛋白、细胞的影响和纳米材料的生物安全性问题,本文综述了近年来纳米骨组织工程支架材料的生物学效应研究进展。     

Fabrication and characterization of hydroxypropyl guar-poly (vinyl alcohol)-nano hydroxyapatite composite hydrogels for bone tissue engineering

Abstract

Biocompatible bone implants composed of natural materials are highly desirable in orthopedic reconstruction procedures. In this study, novel and ecofriendly bionanocomposite hydrogels were synthesized using a blend of hydroxypropyl guar (HPG), poly vinyl alcohol (PVA), and nano-hydroxyapatite (n-HA) under freeze-thaw and mild reaction conditions. The hydrogel materials were characterized using various techniques. TGA studies indicate that both composites, HPG/PVA and HPG/PVA/n-HA, have higher thermal stability compared to HPG alone whereas HPG/PVA/n-HA shows higher stability compared to PVA alone. The HPG/PVA hydrogel shows porous morphology as revealed by the SEM, which is suitable for bone tissue regeneration. Additionally, the hydrogels were found to be transparent and flexible in nature. In vitro biomineralization study performed in simulated body fluid shows HPG/PVA/n-HA has an apatite like structure. The hydrogel materials were employed as extracellular matrices for biocompatibility studies. In vitro cell viability studies using mouse osteoblast MC3T3 cells were performed by MTT, Trypan blue exclusion, and ethidium bromide/acridine orange staining methods. The cell viability studies reveal that composite materials support cell growth and do not show any signs of cytotoxicity compared to pristine PVA. Osteoblastic activity was confirmed by an increased alkaline phosphatase enzyme activity in MC3T3 bone cells grown on composite hydrogel matrices.     

骨组织工程研究

骨缺损、骨不连的修复一直是医学界的棘手问题 ,目前常用的修复方法如人工合成替代物、异体骨移植、自体骨移植等在不同程度上均存在一定的问题 ,如 :供体来源有限、免疫排斥反应等。近年来利用组织工程的原理和方法新生骨组织 ,为骨缺损、骨不连的治疗提供了全新的修复方法[1,2 ] ,是国际上研究的热点之一。组织工程学 (Ｔｉｓｓｕｅｅｎｇｉｎｅｅｒｉｎｇ)是随着细胞生物学和生物材料科学的发展和研究的深入而逐步发展和建立起来的。它是一门利用生命科学和工程学的原理和方法 ,研究正常和病理组织结构和功能的关系 ,研究能够保留、修复…