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1.
血管新生及丝蛋白材料血管化过程   总被引:1,自引:0,他引:1  
基于医用生物材料开发及组织工程中血管化问题的重要性,本文就与生物材料血管化紧密相关的血管发生和血管新生有关研究做一综述,分析了芽式和套迭式血管新生的模式及机制,特别是对丝蛋白材料的血管化过程进行了分析与探讨.通过深入探讨血管新生的模式和机制,进而阐明丝蛋白材料中毛细血管生长与生物材料微结构之间的关系,有助于设计出适合于细胞黏附、组织生长、血管化顺利进行的生物材料,促进生物材料的临床应用及组织工程血管化研究的深化.  相似文献   

2.
神经骨学是近年的研究热点。其中,感觉神经在骨中分布广泛,且在骨修复中具有重要作用,感觉神经与骨的相关性研究引起诸多关注。大段骨缺损修复是骨修复中的一大难点。由于骨缺损中心区域无神经支配和血液供应,导致修复骨缺损的组织工程骨中心易坏死,严重限制大段组织工程骨的发展。近年研究发现,使用感觉神经构建的神经化组织工程骨可以有效修复大段骨缺损。该文就感觉神经在骨修复中的研究现状,以及神经化组织工程骨的最新进展进行综述,为神经骨相关研究提供新思路。  相似文献   

3.
目的:研究血管内皮细胞生长因子(VEGF)联合碱性成纤维细胞生长因子(bFGF)促进兔骨髓基质干细胞向血管内皮样细胞的定向诱导分化,为血管化组织工程骨研究提供实验基础.方法:采集2周龄兔后肢长骨骨髓,用全骨骨髓贴壁法进行原代培养,将获得的第2代骨髓基质干细胞以1× 105/mL密度接种于内皮细胞条件培养基(含10 μg/L VEGF,10 μg/L bFGF,10%胎牛血清的DMEM/F12培养液)进行体外诱导培养,对诱导2周的细胞进行细胞形态观察和表型、功能鉴定.结果:经血管内皮细胞条件培养基诱导2周后的细胞呈扁平形,多边形,表达血管内皮细胞特异性标志CD31、VWF因子,细胞具有吞噬DiI-Ac-LDL和摄取FITC-UEA-1的功能,诱导的细胞可在BD基质胶内形成管腔样结构.结论:血管内皮细胞生长因子联合碱性成纤维细胞生长因子可以成功诱导兔骨髓基质干细胞为血管内皮样细胞,有希望作为组织工程骨的血管化的种子细胞.  相似文献   

4.
内皮祖细胞(EPCs)研究进展   总被引:2,自引:0,他引:2       下载免费PDF全文
组织工程血管以及组织工程化组织的血管化因目前内皮种子细胞扩增能力和生物活力的不足而受到限制。EPCs(内皮祖细胞)是内皮细胞的前体细胞。在胚胎期,内皮细胞系与造血细胞系来源于血岛内共同的祖先细胞;出生后,EPCs存在于骨髓,并可被转移至外周血,参与缺血组织的血管重建和血管的内膜化。因此EPCs有望成为今后组织工程内皮种子细胞的重要来源。  相似文献   

5.
组织工程三大要素为种子细胞、支架材料和信号分子,干细胞因其多分化潜能成为热门的种子细胞。血管化问题是制约工程化组织应用于临床的问题之一。利用干细胞构建组织工程血管的手段之一是在分离培养得到足够的种子细胞后,通过生长因子、细胞外基质、外力作用、其他细胞等的调控实现内皮向分化。只有实现了成功的血管构建,工程化组织才能正常的发挥作用。近年来不少国内外专家学者通过细胞联合培养的方法,观察细胞间的相互作用对血管构建的影响,结果表明,细胞联合培养在血管的形成、存活、稳定方面起到了重要的作用,为组织工程血管化提供了有效的途径,本文就部分细胞联合培养在血管构建中的作用作一综述。  相似文献   

6.
具有三维结构的支架材料是组织工程的核心内容之一。现有组织工程支架可分为天然生物材料、合成有机材料和无机材料三类。支架材料近年来研究十分活跃,不仅在组织工程的最早产品人工皮肤领域进行了更为完善的研究和开发,同时在诸如人工骨、软骨、神经、血管、皮肤、肝、脾、肾、膀胱等方面进行了大量研究和探索。与普通组织工程支架需要预先制备并在体外成型不同,近年来在骨和软骨组织工程实践中兴起的可注射支架具有许多优势,是未来组织工程支架发展的重要方向之一。  相似文献   

7.
骨折愈合是一个独特的多步骤过程,最终可导致正常的骨的解剖和骨的功能的恢复,而不像其他组织修复过程往往最终以瘢痕组织结束。骨折后形成大量修复性骨痂组织,包绕骨折部位。骨痂中存在两种骨形成方式:即膜内化骨和软骨内化骨。系统激素和局部生长因子参与调节骨折愈合过程中的膜内化骨、软骨形成和软骨内化骨。在软骨性骨痂的形成与吸收、骨性骨痂的形成与重塑的动态过程中,新生血管的形成起重要作用。在众多的调节  相似文献   

8.
目前,组织工程化血管的构建和工程化组织器官的血管化因内皮种子细胞的扩增能力不足和生物活性不强而受到限制。内皮祖细胞(EPC)是内皮细胞的前体细胞。出生后,EPC主要存在于骨髓,可向外周血液缓慢释放,参与机体缺血组织的血管重建和损伤血管的重新内皮化。现对EPC的来源、分布、表型特征、动员、分化、归巢、分离、培养与鉴定等生物学特性和EPC在组织工程中的应用进行了全面的综述,并指出目前存在的问题和研究方向。  相似文献   

9.
骨组织工程是通过在体外构建有正常组织功能或疾病生理特点的临床模型,用以药物筛选,或研究疾病发生发展过程。骨骼肌肉系统是载重系统,其功能与组织结构、细胞外基质等密切相关。在构建骨组织体外模型时,需要结合骨、软骨及其他构成成分的生理微环境,表现关节骨软骨接合处的生理特点及作用机制,进而模拟正常及病理状态下骨组织系统对刺激的反应。本综述从骨软骨组织的生理构造入手,阐述了骨软骨连接处在退行性关节病变发生发展过程中的作用,并系统的论述了体外构建三维骨软骨组织的方法及这些方法的优势和局限性,为体外构建骨软骨组织工程在临床上应用提供支持。  相似文献   

10.
骨组织工程通过联合利用种子细胞、生物活性因子和支架材料等要素来构建骨组织再生微环境,从而促进骨缺损的修复重建来诱导骨再生。明胶微球具有多孔性、生物降解性、生物相容性及生物安全性等优势,是一种极具应用潜能的骨修复材料。明胶微球用于体外培养种子细胞时可实现高效扩增。多官能团结构使其可作为促血管再生因子、促骨再生因子及抗感染因子等多种药物的递送载体,缓释药物的同时也可实现微球的多功能化。在构建明胶微球支架时与其他生物材料复合及血管化性能的赋予可提高支架材料的综合性能,但目前支架的设计还存在如何兼顾材料多孔结构和力学性能的问题。本文主要综述了明胶微球的常见制备技术及其近年来在骨组织工程中的应用,并对未来的发展前景进行展望。  相似文献   

11.
Achieving successful vascularization remains one of the main problems in bone tissue engineering. After scaffold implantation, the growth of capillaries into the porous construct may be too slow to provide adequate nutrients to the cells in the scaffold interior and this inhibits tissue formation in the scaffold core. Often, prior to implantation, a controlled cell culture environment is used to stimulate cell proliferation and, once in place, the mechanical environment acting on the tissue construct is determined by the loading conditions at the implantation site. To what extent do cell seeding conditions and the construct loading environment have an effect on scaffold vascularization and tissue growth? In this study, a mechano-biological model for tissue differentiation and blood vessel growth was used to determine the influence of cell seeding on vascular network development and tissue growth inside a regular-structured bone scaffold under different loading conditions. It is predicted that increasing the number of cells seeded homogeneously reduces the rate of vascularization and the maximum penetration of the vascular network, which in turn reduces bone tissue formation. The seeding of cells in the periphery of the scaffold was predicted to be beneficial for vascularization and therefore for bone growth; however, tissue formation occurred more slowly during the first weeks after implantation compared to homogeneous seeding. Low levels of mechanical loading stimulated bone formation while high levels of loading inhibited bone formation and capillary growth. This study demonstrates the feasibility of computational design approaches for bone tissue engineering.  相似文献   

12.
Tissue engineering of bone: the reconstructive surgeon's point of view   总被引:8,自引:0,他引:8  
Bone defects represent a medical and socioeconomic challenge. Different types of biomaterials are applied for reconstructive indications and receive rising interest. However, autologous bone grafts are still considered as the gold standard for reconstruction of extended bone defects. The generation of bioartificial bone tissues may help to overcome the problems related to donor site morbidity and size limitations. Tissue engineering is, according to its historic definition, an "interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function". It is based on the understanding of tissue formation and regeneration and aims to rather grow new functional tissues than to build new spare parts. While reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, and some of the currently developed concepts may represent alternatives to autologous bone grafts for certain clinical conditions, the reconstruction of large-volume defects remains challenging. Therefore vascularization concepts gain on interest and the combination of tissue engineering approaches with flap prefabrication techniques may eventually allow application of bone-tissue substitutes grown in vivo with the advantage of minimal donor site morbidity as compared to conventional vascularized bone grafts. The scope of this review is the introduction of basic principles and different components of engineered bioartificial bone tissues with a strong focus on clinical applications in reconstructive surgery. Concepts for the induction of axial vascularization in engineered bone tissues as well as potential clinical applications are discussed in detail.  相似文献   

13.
BACKGROUND A major problem in the healing of bone defects is insufficient or absent blood supply within the defect.To overcome this challenging problem,a plethora of approaches within bone tissue engineering have been developed recently.Bearing in mind that the interplay of various diffusible factors released by endothelial cells(ECs)and osteoblasts(OBs)have a pivotal role in bone growth and regeneration and that adjacent ECs and OBs also communicate directly through gap junctions,we set the focus on the simultaneous application of these cell types together with platelet-rich plasma(PRP)as a growth factor reservoir within ectopic bone tissue engineering constructs.AIM To vascularize and examine osteogenesis in bone tissue engineering constructs enriched with PRP and adipose-derived stem cells(ASCs)induced into ECs and OBs.METHODS ASCs isolated from adipose tissue,induced in vitro into ECs,OBs or just expanded were used for implant construction as followed:BPEO,endothelial and osteogenic differentiated ASCs with PRP and bone mineral matrix;BPUI,uninduced ASCs with PRP and bone mineral matrix;BC(control),only bone mineral matrix.At 1,2,4 and 8 wk after subcutaneous implantation in mice,implants were extracted and endothelial-related and bone-related gene expression were analyzed,while histological analyses were performed after 2 and 8 wk.RESULTS The percentage of vascularization was significantly higher in BC compared to BPUI and BPEO constructs 2 and 8 wk after implantation.BC had the lowest endothelial-related gene expression,weaker osteocalcin immunoexpression and Spp1 expression compared to BPUI and BPEO.Endothelial-related gene expression and osteocalcin immunoexpression were higher in BPUI compared to BC and BPEO.BPEO had a higher percentage of vascularization compared to BPUI and the highest CD31 immunoexpression among examined constructs.Except Vwf,endothelial-related gene expression in BPEO had a later onset and was upregulated and well-balanced during in vivo incubation that induced late onset of Spp1 expression and pronounced osteocalcin immunoexpression at 2 and 8 wk.Tissue regression was noticed in BPEO constructs after 8 wk.CONCLUSION Ectopically implanted BPEO constructs had a favorable impact on vascularization and osteogenesis,but tissue regression imposed the need for discovering a more optimal EC/OB ratio prior to considerations for clinical applications.  相似文献   

14.
To achieve the goals of engineering large complex tissues, and possibly internal organs, vascularization of the regenerating tissue is essential. To maintain the initial volume after implantation of regenerated tissue, improved vascularization is considered to be important. Recent advances in understanding the process of blood vessel growth has offered significant tools for the neovascularization of bioengineered tissues and therapeutic angiogenesis. Several angiogenic growth factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) were used for vascularization of ischemic tissues. Other approaches such as prevascularization of the scaffold, prior to cell seeding, and incorporation of endothelial cells in the bioengineered tissue showed encouraging results. In this article, we will review recent advances in angiogenic growth factors, and discuss the role of these growth factors and endothelial cells in therapeutic angiogenesis and tissue engineering.  相似文献   

15.
Principals of neovascularization for tissue engineering   总被引:31,自引:0,他引:31  
The goals in tissue engineering include the replacement of damaged, injured or missing body tissues with biological compatible substitutes such as bioengineered tissues. However, due to an initial mass loss after implantation, improved vascularization of the regenerated tissue is essential. Recent advances in understanding the process of blood vessel growth has offered significant tools for therapeutic neovascularization. Several angiogenic growth factors including vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) were used for vascularization of ischemic tissues. Three approaches have been used for vascularization of bioengineered tissue: incorporation of angiogenic factors in the bioengineered tissue, seeding endothelial cells with other cell types and prevascularization of matrices prior to cell seeding. This paper reviews the process of blood vessel growth and tissue vascularization, and discuss strategies for efficient vascularization of engineered tissues.  相似文献   

16.
Rafii S  Lyden D 《Nature medicine》2003,9(6):702-712
Emerging evidence suggests that bone marrow-derived endothelial, hematopoietic stem and progenitor cells contribute to tissue vascularization during both embryonic and postnatal physiological processes. Recent preclinical and pioneering clinical studies have shown that introduction of bone marrow-derived endothelial and hematopoietic progenitors can restore tissue vascularization after ischemic events in limbs, retina and myocardium. Corecruitment of angiocompetent hematopoietic cells delivering specific angiogenic factors facilitates incorporation of endothelial progenitor cells (EPCs) into newly sprouting blood vessels. Identification of cellular mediators and tissue-specific chemokines, which facilitate selective recruitment of bone marrow-derived stem and progenitor cells to specific organs, will open up new avenues of research to accelerate organ vascularization and regeneration. In addition, identification of factors that promote differentiation of the progenitor cells will permit functional incorporation into neo-vessels of specific tissues while diminishing potential toxicity to other organs. In this review, we discuss the clinical potential of vascular progenitor and stem cells to restore long-lasting organ vascularization and function.  相似文献   

17.
《Cytotherapy》2020,22(8):400-411
Tissue defects in the human body after trauma and injury require precise reconstruction to regain function. Hence, there is a great demand for clinically translatable approaches with materials that are both biocompatible and biodegradable. They should also be able to adequately integrate within the tissue through sufficient vascularization. Adipose tissue is abundant and easily accessible. It is a valuable tissue source in regenerative medicine and tissue engineering, especially with regard to its angiogenic potential. Derivatives of adipose tissue, such as microfat, nanofat, microvascular fragments, stromal vascular fraction and stem cells, are commonly used in research, but also clinically to enhance the vascularization of implants and grafts at defect sites. In plastic surgery, adipose tissue is harvested via liposuction and can be manipulated in three ways (macro-, micro- and nanofat) in the operating room, depending on its ultimate use. Whereas macro- and microfat are used as a filling material for soft tissue injuries, nanofat is an injectable viscous extract that primarily induces tissue remodeling because it is rich in growth factors and stem cells. In contrast to microfat that adds volume to a defect site, nanofat has the potential to be easily combined with scaffold materials due to its liquid and homogenous consistency and is particularly attractive for blood vessel formation. The same is true for microvascular fragments that are easily isolated from adipose tissue through collagenase digestion. In preclinical animal models, it has been convincingly shown that these vascular fragments inosculate with host vessels and subsequently accelerate scaffold perfusion and host tissue integration. Adipose tissue is also an ideal source of stem cells. It yields larger quantities of cells than any other source and is easier to access for both the patient and doctor compared with other sources such as bone marrow. They are often used for tissue regeneration in combination with biomaterials. Adipose-derived stem cells can be applied unmodified or as single cell suspensions. However, certain pretreatments, such as cultivation under hypoxic conditions or three-dimensional spheroids production, may provide substantial benefit with regard to subsequent vascularization in vivo due to induced growth factor production. In this narrative review, derivatives of adipose tissue and the vascularization of biomaterials are addressed in a comprehensive approach, including several sizes of derivatives, such as whole fat flaps for soft tissue engineering, nanofat or stem cells, their secretome and exosomes. Taken together, it can be concluded that adipose tissue and its fractions down to the molecular level promote, enhance and support vascularization of biomaterials. Therefore, there is a high potential of the individual fat component to be used in regenerative medicine.  相似文献   

18.
Stahl A  Wu X  Wenger A  Klagsbrun M  Kurschat P 《FEBS letters》2005,579(24):5338-5342
Survival of tissue transplants generated in vitro is strongly limited by the slow process of graft vascularization in vivo. A method to enhance graft vascularization is to establish a primitive vascular plexus within the graft prior to transplantation. Endothelial cells (EC) cultured as multicellular spheroids within a collagen matrix form sprouts resembling angiogenesis in vitro. However, osteoblasts integrated into the graft suppress EC sprouting. This inhibition depends on direct cell-cell-interactions and is characteristic of mature ECs isolated from preexisting vessels. In contrast, sprouting of human blood endothelial progenitor cells is not inhibited by osteoblasts, making these cells suitable for tissue engineering of pre-vascularized bone grafts.  相似文献   

19.
Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues.  相似文献   

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