The Role of Bone Morphogenetic Proteins in Tissue Engineering Particulate Bone Grafts

Bone defects of various causes are important medical and socioeconomical problems because of the impossibility of spontaneous healing, difficult treatment, and long healing period. There are multiple, varied, and relatively complicated ways of solving these problems. Over time, numerous investigations carried out have shown failures arising from the use of autografts and homografts. The disadvantages of these methods prompted a search for other methods of bone reconstruction. Bone substitutes can play an important role in bone reconstructive surgery. In this context, tissue engineering bone grafts has offered an alternative. The aim of our research was to evaluate the feasibility of creating a tissue-engineered bone using mesenchymal stem cells seeded on a scaffold obtained from the red deer deciduous horn. We tried to demonstrate the advantages of using bone morphogenetic proteins (BMP-2) and transforming growth factor β (TGF-β) as promoters of the differentiation process. Our study was carried out on animal model, an outbred CD 1 mouse strain. Our research demonstrated that supplementation with growth factors (BMP-2, TGF-β) in osteogenic medium improved and accelerated bony-line differentiation and mineralization process. The same factors accelerated and stabilized the osteoblast differentiation and inhibit different lineage appearance such as myeloid metaplasia.     

壳聚糖对骨组织工程中组织修复的影响

材料植入体内必然引起宿主体的应答,促进或抑制组织愈合。由于降解材料在体内的降解产物会随时间而变,产生的宿主体应答就会不同,进而会影响组织的愈合。而促进或抑制组织愈合的机制就成为新型医用高分子材料设计和制备的理论基础。壳聚糖是理想的骨组织修复材料之一,但至今还不清楚壳聚糖体内不同降解过程对组织修复的影响机制,也就无法设计出性能优良的壳聚糖基新材料。文章没有罗列壳聚糖基生物材料在骨组织工程中应用所取得的进展,而是重点阐述了壳聚糖在骨组织工程中应用的复杂性和对组织修复的影响,探讨了壳聚糖进一步用于骨组织工程所需要解决的问题。     

骨组织工程支架材料及其力学性能

骨组织工程的研究是组织工程最为活跃的领域之一,如何制备理想的骨支架材料是当前的一个研究热点.通过人们的努力,目前已有多种骨组织工程支架材料问世.综述了各类骨组织工程支架材料的优缺点,对比了它们的力学性能,并对骨组织工程的前景进行了展望.     

骨组织工程支架材料的研究进展

骨组织工程的发展,要求充分结合材料工程与生物工程相关知识,对植入材料进行分子及细胞水平的设计.细胞外基质材料(支架材料)的选择与制备是骨组织工程的一项重要而关键的任务.如何找到能促进并指导细胞黏附、增殖的支架材料是目前骨组织工程研究的热点之一.介绍了骨组织工程相关原理,并综述了几种支架材料的发展研究现状.     

羟基磷灰石/羧甲基壳聚糖组织工程骨的制备及表征

以京尼平(Genipin)为交联剂,通过粒子沥滤结合冷冻干燥工艺制备纳米羟基磷灰石/羧甲基壳聚糖复合支架。然后依据组织工程的原则,将pcDNA3.1-血管内皮生长因子(Vascular endothelial growth factor,VEGF)165质粒转染后的骨髓间充质干细胞(Bone marrow stromal cells,BMSCs)与支架复合构建组织工程骨。最后将该组织工程骨植入到兔桡侧,观察其成骨能力及降解速度。结果表明:京尼平交联的支架材料的微观结构、力学性能与天然松质骨相似,可满足支架材料的要求;且支架材料具有自发荧光特征,便于观察支架的微结构及界面上细胞的粘附情况;动物实验表明所得复合骨具有生物相容性好、无毒副作用的优点及促进局部微血管形成、加快骨缺损修复的作用,其降解速度与骨生长速度基本匹配,是一种潜在的性能优良的骨修复材料。     

骨组织工程支架材料的研究进展

综述了骨组织工程支架材料在骨缺损治疗的研究现状,并展望了其未来的发展方向。利用各种材料的优势互补性,将两种或两种以上材料通过恰当的方式组合成复合支架材料,其力学性能和降解速率可根据各组分材料的种类、数量及组合方法的变化进行调节,按照要求制备出具有一定机械强度和降解速率的支架材料。并指出骨组织工程复合支架材料将会成为骨缺损修复中一类富有潜力的生物材料。     

有机-无机复合骨重建材料的研究进展

骨组织重建技术的进步与材料科学的发展息息相关，对国内外当前非金属骨植入与骨组织工程材料的种类及其复合技术的研究情况进行了综述与评价，认为对界面结合的研究、新的智能型材料的研究是今后非金属复合骨重建材料的发展方向。     

组织工程用生物材料与系统

当今以工程科学、生命科学原理开发修复、维持或改善组织功能的生物取代物为目标的组织工程正引起先进国家官、产、学各方面的关注，此高新技术不仅能显著提高对疾患的诊治水平，更能形成组织工程产品市场。本文结合１９９６年在加拿大多伦多举行的第５届世界生物材料大会期间举办的组织工程科学展示会为经纬，介绍相关的研究与开发进展。     

Thermo-Responsive Nanocomposite Bioink with Growth-Factor Holding and its Application to Bone Regeneration

Three-dimensional (3D) bioprinting, which is being increasingly used in tissue engineering, requires bioinks with tunable mechanical properties, biological activities, and mechanical strength for in vivo implantation. Herein, a growth-factor-holding poly(organophosphazene)-based thermo-responsive nanocomposite (TNC) bioink system is developed. The mechanical properties of the TNC bioink are easily controlled within a moderate temperature range (5–37 °C). During printing, the mechanical properties of the TNC bioink, which determine the 3D printing resolution, can be tuned by varying the temperature (15–30 °C). After printing, TNC bioink scaffolds exhibit maximum stiffness at 37 °C. Additionally, because of its shear-thinning and self-healing properties, TNC bioinks can be extruded smoothly, demonstrating good printing outcomes. TNC bioink loaded with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta1 (TGF-β1), key growth factors for osteogenesis, is used to print a scaffold that can stimulate biological activity. A biological scaffold printed using TNC bioink loaded with both growth factors and implanted on a rat calvarial defect model reveals significantly improved bone regenerative effects. The TNC bioink system is a promising next-generation bioink platform because its mechanical properties can be tuned easily for high-resolution 3D bioprinting with long-term stability and its growth-factor holding capability has strong clinical applicability.     

骨组织工程支架-多孔β-磷酸三钙陶瓷的制备与性能

本文通过多孔β-磷酸三钙陶瓷的性能研究，发现将孔度提高到40％以上、孔径在100～500微米之间时，陶瓷还保持一定强度；X-射线衍射证实陶瓷组成为β—磷酸三钙晶体。预期该支架可用作骨组织工程支架。     

ACF/PLGA骨组织工程复合支架的制备及其性能

本文利用溶剂灌制/粒子沥滤的方法将具有较强吸附性能的活性碳纤维(activated carbon fiber,ACF)掺杂于聚乳酸-羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)制备了一种新型ACF/PLGA骨组织工程复合支架。论文对比研究了纯PLGA支架以及两种ACF/PLGA支架(ACF含量为2.75%,8.26%)的结构和性能。SEM研究发现三者都具有较高的孔隙度,分别为73.5340%、75.1214%和79.8216%,且孔隙度随着ACF含量的增加逐渐增大;压汞法测得三者的孔径分布基本在50~250μm之间;研究其亲水性发现,其表面接触角随ACF含量增加逐渐减小,吸水率则逐渐增大。进一步研究发现在三种支架上种植小鼠成纤维细胞(L929),一天后细胞都较好粘附在支架上;ACF含量为8.26%的复合支架移植到小白鼠皮下组织,一月后HE切片显示支架周围组织的免疫排斥反应较小。掺杂ACF的PLGA复合支架除了具有良好的细胞粘附效果和组织相容性,相对于纯PLGA支架,还具有良好的孔径分布和亲水性,具有潜在的应用价值。     

多孔镁作为新型骨组织工程材料的研究探索

多孔镁作为骨组织工程材料具有明显的优势.介绍了多孔镁的制备方法,评述了镁基材料作为骨组织工程材料的生物相容性以及在其表面可能制备的生物活性涂层,初步探讨了镁基材料在体内的降解机理,并对多孔镁作为一种新型骨组织工程材料的医用前景进行了展望.     

骨组织工程支架的制造

支架的研究一直是骨组织工程研究的主要问题之一，到目前为止已经开发出了不少比较成熟的支架制作技术，但是这些技术都还存在一定的缺陷，快速成形技术由于具有快速性和高度柔性的突出优点，因而在支架制造方面具有广泛的应用前景，清华大学已经在这个方面进行了大量的基础性研究。     

一种组织工程材料的制备及性能表征

以异氰酸酯(MDI)作为相容剂,采用共混挤出技术制备不同百分含量的聚己内酯(PCL)与淀粉的共混产物(SPCL)作为研究对象,对材料的力学性能、组成、微观结构、结晶性质和热性能进行表征,重点考察了材料的亲水性能和降解性能。结果表明,MDI明显改善了淀粉和PCL两相的相容性,淀粉的存在增加了SPCL羟基基团的数量,降低了材料的力学性能,同时抑制了PCL的结晶,降低了材料的熔点,提高了材料亲水性能,加快了材料在Hank′s平衡盐溶液(HBSS)中的降解速度。表明SPCL是一种有广泛应用前景的组织工程植入修复材料。     

Titanium Fiber Plates for Bone Tissue Repair

Titanium plates are widely used in clinical settings because of their high bone affinity. However, owing to their high elastic modulus, these plates are not suitable for bone repair since their proximity to the bone surface for prolonged periods can cause stress shielding, leading to bone embrittlement. In contrast, titanium fiber plates prepared by molding titanium fibers into plates by simultaneously applying compression and shear stress at normal room temperature can have an elastic modulus similar to that of bone cortex, and stress shielding will not occur even when the plate lies flush against the bone's surface. Titanium fibers can form a porous structure suitable for cell adhesion and as a bone repair scaffold. A titanium fiber plate is combined with osteoblasts and shown that the titanium fiber plate is better able to facilitate bone tissue repair than the conventional titanium plate when implanted in rat bone defects. Capable of being used in close contact with bone for a long time, and even capable of promoting bone repair, titanium fiber plates have a wide range of applications, and are expected to make great contributions to clinical management of increasing bone diseases, including bone fracture repair and bone regenerative medicine.     

Tissue Engineering Strategies Designed to Realize the Endogenous Regenerative Potential of Peripheral Nerves

http://doi.wiley.com/10.1002/adma.v21:32/33 Bridging peripheral nerve gaps without the use of autografts has significant clinical importance. But in order to rationally design novel scaffolds, a good understanding of the nerve regeneration process is vital. Appropriate amount of structural and chemical cues are required to stimulate the endogenous mechanisms of repair and functional recovery. Synthetic and natural materials present various opportunities to induce the growth of supporting cells as well as promote axon regeneration. An overview of tissue engineering strategies currently being explored that stimulate the different steps of the regenerative sequence is presented.     

Glass,Ceramic, Polymeric,and Composite Scaffolds with Multiscale Porosity for Bone Tissue Engineering

Porosity affects performance of scaffolds for bone tissue engineering both in vitro and in vivo. Macropores (i.e., pores with a diameter >100 μm) are essential for cellular infiltration; micropores (i.e., pores with a diameter of 1–10 μm) promote cell adhesion and facilitate nutrient absorption. Scaffolds containing both macropores and micropores exploit the advantages of both pore sizes and have excellent osteogenic properties. Nanopores (i.e., pores with a diameter of 1–50 nm) can be included as well, to improve cell–material interactions by further enhancing the surface area of the scaffold. This article reviews fabrication techniques and properties of scaffolds with multiscale porosity, focusing on glass, ceramic, polymeric, and composite scaffolds. After discussing the structure of bone and how it inspired scaffolds for bone tissue engineering, pore nomenclature is introduced. Then, the techniques used to induce multiscale porosity, the nature of the pores created, and the effects of scaffold porosity on mechanical properties and biological activity of the scaffolds are discussed. The review concludes by providing an outlook for this field, including advancements that are made possible by computational modeling and artificial intelligence.     

硬组织修复材料的骨再生机理研究

传统硬组织修复材料由于在组成及结构上与人体骨组织存在较大差异,植入体内后的骨组织修复过程基本上是一种被动的"充填"过程,且材料的降解速度与新骨形成速度不匹配,难以达到真正的"生物性融合",严重制约了该类材料在骨科临床的推广应用。因此,设计与制备具有"主动修复功能"和"可调控生物响应特性"的第3代新型硬组织修复材料已成为当前骨科临床的新需求和未来的发展方向。介绍了硬组织修复材料的骨再生机理研究方法,综述了硬组织修复材料与宿主防御和骨再生及宿主微环境对材料与宿主细胞相互作用的研究现状。指出硬组织修复材料植入体内后所发生的序列事件可能通过表观遗传修饰使得基因表达受材料本身和宿主微环境等因素的调控,提出新型硬组织修复材料研究中存在的问题和发展趋势。     

中枢神经再生材料研究进展

首先介绍了目前中枢神经再生面临的问题和应对策略,然后系统地综述了脑再生和脊髓再生修复材料的发展。研究发现,成人中枢神经系统内存的神经干细胞和具有特定分化方向的前体细胞具有潜在的、巨大的修复功能;生物支架材料与神经干细胞的联合使用能够较好地控制细胞微环境,有望提高细胞移植后的存活状况,促进中枢神经再生。最后,结合现在中枢神经再生的研究热点——神经干细胞,阐述了中枢神经再生材料调控干细胞的研究进展和潜能,为联合应用生物材料与干细胞促进中枢再生提供了参考。