脱细胞基质水凝胶促组织再生的研究进展

脱细胞基质水凝胶是组织或器官通过物理、化学和酶解等手段去除其细胞的内容物,只保留细胞骨架结构和细胞外基质等成分,以实现促细胞黏附、增殖和分化并为其生长创造良好微环境的天然高分子生物材料。近年来,由于其良好的细胞相容性、生物可降解性和诱导组织再生能力,脱细胞基质水凝胶在组织修复、再生医学领域备受关注。首先,介绍该水凝胶的基本特点和材料特性,包括其内部的组成成分和结构、组织特异性以及潜在的免疫排斥反应;然后,从细胞水平的培养、临床前的研究和临床上的应用等三方面,重点阐述脱细胞基质水凝胶在组织工程学中的研究应用;最后,展望脱细胞基质材料运用的优势和需要克服的缺陷。总之,作为构建工程化组织以及修复组织缺损的新型生物活性材料,脱细胞基质水凝胶具有广阔的应用前景。     

利用水凝胶设计组织再生微环境

水凝胶如何为细胞、组织的生长提供三维微环境已成为组织工程和再生医学领域的研究热点,生物活性分子修饰获得的智能水凝胶是能够促进组织再生的重要生物材料。根据水凝胶的来源,可将其分为天然和合成水凝胶两种类型。水凝胶的设计策略主要包括凝胶降解敏感位点的设计、生物黏附性的获得、生长因子和细胞因子对凝胶的修饰以及再生组织的血管重建。此外,本文以智能水凝胶在软骨组织工程、神经组织工程等方面的应用为例,阐述了水凝胶在组织工程和再生医学领域的突出研究进展。     

水凝胶的生物力学研究进展

水凝胶是生物医用领域的重要生物材料,也是近年来的研究热点。但人体内的细胞与组织的微环境和调控机制非常复杂,水凝胶应用于再生修复领域仍存在一些待解决的科学问题。随着生物力学的发展,越来越多的研究者发现除了关注水凝胶的材料学及生物学特性以外,其生物力学特性也是调控细胞功能、影响组织再生修复的关键因素之一。因此,本文总结了水凝胶材料的生物力学研究进展,并对未来的研究工作进行了展望。     

基于生物活性玻璃的生物复合材料研究进展EI北大核心

生物活性玻璃(BG)具有优良的生物性能且无细胞毒性,可促进骨和软组织再生,近年来已广泛应用于人工骨支架的制备。但由于玻璃材料多存在脆性大、机械强度差、易团聚且结构不可控等缺点,使其在各领域中的应用受到限制。对此,当前大多数研究主要聚焦于采用冷冻干燥法、溶胶凝胶法等将其与有机或无机材料进行混合,以改善BG的机械性能及其脆性等,进而增加其临床应用、拓展其应用领域。本文通过介绍BG与天然有机材料、金属材料、非金属材料结合形成复合材料,及进一步开发其作为支架、注射填充剂、膜、水凝胶和涂层等产品的方式,展现了当前领域内制备BG复合材料的最新技术和应用前景。研究分析表明,BG的加入改善了原有材料的机械性能及其生物活性和再生潜力,拓宽了BG在骨组织工程领域的应用。本文通过回顾近年来BG在骨再生研究方面的研究进展,展现了BG在新材料研发领域的潜力,以期为今后的相关研究提供参考借鉴。     

多肽水凝胶在牙髓再血管化中的应用进展

近年来,根管治疗后出现的牙髓活力丧失、牙齿脆性增加和牙体易折裂等问题逐渐引起重视,牙髓再生成为牙髓病和根尖周病治疗领域的研究热点。牙髓再生中的血管再生是重中之重。研究发现多肽水凝胶支架材料既能影响细胞行为,促进血管生成,还可以根据需要进行改性,应用灵活,受到了广泛关注。主要对离子互补性多肽、表面活性剂类多肽和化学基团修饰类多肽在牙髓再血管化中的应用进展进行综述,总结多肽水凝胶支架材料的特点,为其在牙髓再生中的进一步应用提供一定借鉴。     

甲基纤维素基温敏水凝胶在生物医学领域的研究进展

甲基纤维素（MC）是一种半柔性纤维素醚衍生物,其水凝胶温敏可逆,生物相容性良好,功能可调,其应用在生物医学领域备受关注。本文对甲基纤维素温敏水凝胶在生物医学领域的应用进展进行了综述。在对甲基纤维素的凝胶化机制及凝胶化影响因素进行论述的基础上,重点介绍了甲基纤维素基水凝胶在生物医学领域的应用进展,包括在药物递送、再生医学及其他方面等的应用,列表总结了相关领域的成果,为后续研究提供思路和方向。最后,还讨论了甲基纤维素基多功能水凝胶材料的未来发展。     

人发角蛋白在再生医学中的应用研究进展

角蛋白具有可生物降解、生物活性高和相容性好的优势,从人发中提取的角蛋白还具有低免疫排异性.相对于其他本体材料,其来源几乎不受限制,因而在再生医学领域的研究应用受到越来越多的重视.近年来,人发角蛋白以凝胶、海绵支架、涂层、膜以及复合材料的形式应用于神经材料、皮肤敷料、细胞培养、药物载体以及软组织修复等方面,显示出其在再生医学领域的发展潜力.     

凝胶材料制备方法及其反应动力学的研究进展

部分水凝胶材料具有良好的生物相容性、低细胞毒性和生物可降解性,广泛应用于组织工程和生物医药等领域,其中采用天然高分子明胶、壳聚糖和海藻酸钠制备复合凝胶材料,负载骨髓间充质干细胞用于修复和治疗骨缺损成为近年来的研究热点之一。因为水凝胶材料抗张强度低和化学稳定性差,所以研究凝胶反应机理和凝胶反应动力学对提高水凝胶的性能具有重要意义。本文总结了明胶、壳聚糖和海藻酸钠凝胶材料的制备方法和凝胶反应机理,比较了不同凝胶反应动力学研究方法,介绍凝胶复合材料在骨修复中的应用,为天然高分子凝胶材料的分子设计和临床应用提供思路。     

高分子水凝胶修复关节软骨损伤:安全与有效性评价

背景:高分子水凝胶与关节软骨的细胞外基质组成相似,可促进软骨细胞增殖、分化,形成软骨板,促进关节软骨的再生和修复。目的:阐述几种可降解天然高分子水凝胶及其在关节软骨修复组织工程中的最新研究进程及成果。方法:以"natural polymers,biodegradable polymers,hydrogel scaffold,articular cartilage,regeneration;关节软骨,水凝胶,天然聚合物,组织工程"为检索词,应用计算机检索从1994年1月至2013年7月PubMed数据库、Springer数据库、Sciencedirect数据库、Ovid数据库及CNKI数据库发表的天然高分子水凝胶材料相关文献。结果与结论:天然高分子水凝胶材料包括蛋白质类(胶原蛋白、明胶)及多糖类(壳聚糖、透明质酸)等。改性后天然高分子水凝胶不但具备关节软骨再生的理化特性,而且具有良好的生物特性,即组织相容性、低免疫原性、低细胞毒性、自身可降解性,同时可促进细胞黏附、增殖与分化,具备推动新组织再生的能力,甚至能够作为药物、生长因子等的缓释载体,在关节软骨再生及修复领域有着可观的应用前景。     

苏州大学研制成功新型体温响应智能水凝胶

正生物医用材料是21世纪新材料产业发展的主要方向之一,是现代临床医学的重要物质基础。可注射温度感应智能生物材料体系给传统医学带来革新,具备微创植入、智能给药等优势;临床使用便捷、治疗更有效,经济和社会效益显著。在863计划"再生医学前沿技术与应用研究"重点项目的支持下,中国科学家对引导组织再生的新型体温响应智能水凝胶进行了系列研究,并取得重要进展。     

超快动态交联的可注射壳聚糖-透明质酸水凝胶及促创伤愈合研究

可注射动态水凝胶是近年研究的热点,而制备无催化剂体系的快速交联的可注射动态水凝胶是研究的难点之一。以甲基丙烯酰化壳聚糖(CHMA)和醛基化透明质酸(ALHA)为原料,利用CHMA分子上的氨基与ALHA分子上的醛基和羧基,分别形成可逆动态席夫碱键和静电相互作用,可快速制备一种水凝胶。通过动态流变分析仪表征其凝胶化速率、剪切变稀行为和自愈合特征,通过体外细胞三维培养实验评估其细胞相容性,并通过急性全层皮肤创伤修复实验对其创伤愈合速率进行评估。结果表明,只需5 s,CHMA和ALHA的混合溶液就能形成凝胶。此外,该凝胶具有剪切变稀和快速自愈合的可注射特征,当扫描频率从10^-1 s^-1增加至10² s^-1时,其复数黏度由0.4 kPa降低至8 Pa;当应变在1%~1000%之间交替变化时,储能模量与损耗模量的大小能够迅速切换,且模量没有显著性地降低。同时,体外细胞三维培养实验表明,该水凝胶还具有优异的细胞相容性(细胞存活率高于95%),并且在雄性ICR小鼠急性全层皮肤缺损模型实验中,水凝胶组的创伤愈合时间相比空白对照组缩短5～7 d,表现出较快的创伤愈合速率。综上可见,这种可注射壳聚糖-透明质酸水凝胶在生物医药、组织功能、临床医学等领域具有广阔的应用前景。     

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.     

Alginate-based microcapsules generated with the coaxial electrospray method for clinical application

Alginate-based microencapsulation of cells has made a significant impact on the fields of regenerative medicine and tissue engineering mainly because of its ability to provide immunoisolation for the encapsulated material. This characteristic has allowed for the successful transplantation of non-autologous cells in several clinical trials for life threatening conditions, such as diabetes, myocardial infarction, and neurodegenerative disorders. Methods for alginate hydrogel microencapsulation have been well developed for various types of cells and can generate microcapsules of different diameters, degradation time, and composition. It appears the most prominent and successful method in clinical applications is the coaxial electrospray method, which can be used to generate both homogenous and non-homogeneous microcapsules with uniform size on the order of 100 μm. The present review aims to discuss why alginate hydrogel is an ideal biomaterial for the encapsulation of cells, how alginate-based microcapsules are generated, and methods of modifying the microcapsules for specific clinical treatments. This review will also discuss clinical applications that have utilized alginate-based microencapsulation in the treatment of diabetes, ischemic heart disease, and neurodegenerative diseases.     

Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing

Organ printing, a novel approach in tissue engineering, applies layered computer-driven deposition of cells and gels to create complex 3-dimensional cell-laden structures. It shows great promise in regenerative medicine, because it may help to solve the problem of limited donor grafts for tissue and organ repair. The technique enables anatomical cell arrangement using incorporation of cells and growth factors at predefined locations in the printed hydrogel scaffolds. This way, 3-dimensional biological structures, such as blood vessels, are already constructed. Organ printing is developing fast, and there are exciting new possibilities in this area. Hydrogels are highly hydrated polymer networks used as scaffolding materials in organ printing. These hydrogel matrices are natural or synthetic polymers that provide a supportive environment for cells to attach to and proliferate and differentiate in. Successful cell embedding requires hydrogels that are complemented with biomimetic and extracellular matrix components, to provide biological cues to elicit specific cellular responses and direct new tissue formation. This review surveys the use of hydrogels in organ printing and provides an evaluation of the recent advances in the development of hydrogels that are promising for use in skeletal regenerative medicine. Special emphasis is put on survival, proliferation and differentiation of skeletal connective tissue cells inside various hydrogel matrices.     

Hydrogel macroporosity and the prolongation of transgene expression and the enhancement of angiogenesis

The utility of hydrogels for regenerative medicine can be improved through localized gene delivery to enhance their bioactivity. However, current systems typically lead to low-level transgene expression located in host tissue surrounding the implant. Herein, we investigated the inclusion of macropores into hydrogels to facilitate cell ingrowth and enhance gene delivery within the macropores in?vivo. Macropores were created within PEG hydrogels by gelation around gelatin microspheres, with gelatin subsequently dissolved by incubation at 37?°C. The macropores were interconnected, as evidenced by homogeneous cell seeding in?vitro and complete cell infiltration in?vivo. Lentivirus loaded within hydrogels following gelation retained its activity relative to the unencapsulated control virus. In?vivo, macroporous PEG demonstrated sustained, elevated levels of transgene expression for 6 weeks, while hydrogels without macropores had transient expression. Transduced cells were located throughout the macroporous structure, while non-macroporous PEG hydrogels had transduction only in the adjacent host tissue. Delivery of lentivirus encoding for VEGF increased vascularization relative to the control, with vessels throughout the macropores of the hydrogel. The inclusion of macropores within the hydrogel to enhance cell infiltration enhances transduction and influences tissue development, which has implications for multiple regenerative medicine applications.     

介入再生医学中干细胞治疗研究进展

介入再生医学(IRM)是一门通过影像引导微创手术与干细胞的局部递送实现受损器官修复和再生的交叉学科。近年来,基于干细胞的再生治疗已在多项疾病的临床试验中显示出应用前景,然而,通过静脉输入的干细胞会大量聚集于肺和网状内皮系统中,仅有少量细胞能够到达靶组织,使干细胞的临床应用效果难以实现,局部靶向递送是一种有效解决方案。IRM旨在通过经血管内注射、腔内注射或直接注射,将干细胞靶向递送到目标组织器官,提高干细胞再生治疗的功效。综述了再生治疗中常用的干细胞来源、干细胞靶向递送涉及的疾病类型、递送途径和作用机制,展示了IRM中干细胞治疗的研究进展和发展趋势,并对IRM的应用前景及其转化所面临的挑战进行展望和总结。     

Smart biomaterials design for tissue engineering and regenerative medicine

As a prominent tool in regenerative medicine, tissue engineering (TE) has been an active field of scientific research for nearly three decades. Clinical application of TE technologies has been relatively restricted, however, owing in part to the limited number of biomaterials that are approved for human use. While many excellent biomaterials have been developed in recent years, their translation into clinical practice has been slow. As a consequence, many investigators still employ biodegradable polymers that were first approved for use in humans over 30 years ago. During normal development tissue morphogenesis is heavily influenced by the interaction of cells with the extracellular matrix (ECM). Yet simple polymers, while providing architectural support for neo-tissue development, do not adequately mimic the complex interactions between adult stem and progenitor cells and the ECM that promote functional tissue regeneration. Future advances in TE and regenerative medicine will depend on the development of "smart" biomaterials that actively participate in the formation of functional tissue. Clinical translation of these new classes of biomaterials will be supported by many of the same evaluation tools as those developed and described by Professor David F. Williams and colleagues over the past 30 years.     

Thermoresponsive poly(N-isopropylacrylamide)-g-methylcellulose hydrogel as a three-dimensional extracellular matrix for cartilage-engineered applications

Recent advances in tissue engineering and regenerative medicine fields can offer alternative solutions to the existing techniques for cartilage repair. In this context, a variety of materials has been proposed, and the injectable hydrogels are among the most promising alternatives. The aim of this work is to explore the ability of poly(N-isopropylacrylamide)-g-methylcellulose (PNIPAAm-g-MC) thermoreversible hydrogel as a three-dimensional support for cell encapsulation toward the regeneration of articular cartilage through a tissue engineering approach. The PNIPAAm-g-MC copolymer was effectively obtained using ammonium-persulfate and N,N,N',N'-tetramethylethylenediamine as initiator as confirmed by Fourier transform infrared spectroscopy and (1) H NMR results. The copolymer showed to be temperature responsive, becoming a gel at temperatures above its lower critical solution temperature (~ 32 °C) while turning into a liquid below it. Results obtained from the MTS test showed that extracts of the hydrogel were clearly noncytotoxic to L929 fibroblast cells. ATDC5 cells, a murine chondrogenic cell line, were used as the in vitro model for this study; they were encapsulated at high cell density within the hydrogel and cultured for up to 28 days. PNIPAAm-g-MC did not affect the cell viability and proliferation, as indicated by both MTS and DNA assays. The results also revealed an increase in synthesis of glycosoaminoglycans within culture time measured by the dimethylmethylene blue quantification assay. These results suggest the viability of using PNIPAAm-g-MC thermoresponsive hydrogel as a three-dimensional scaffold for cartilage tissue engineering using minimal-invasive strategies.     

Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed.     

Fibrin in Reproductive Tissue Engineering: A Review on Its Application as a Biomaterial for Fertility Preservation

In recent years, reproductive medicine has made good use of tissue engineering and regenerative medicine techniques to develop alternatives to restore fertility in cancer patients. For young female cancer patients who cannot undergo any of the currently applied strategies due to the possible presence of malignant cells in their ovaries, the challenge is creating an in vitro or in vivo artificial ovary using carefully selected biomaterials. Thanks to its numerous qualities, fibrin has been widely used as a scaffold material for fertility preservation applications. The goal of this review is to examine and discuss the applications and advantages of this biopolymer for fertility restoration in cancer patients, and consider the main results achieved so far.