细菌纤维素支架的复合改性及生物性能

采用原花青素交联和仿生矿化技术,以生物相容性良好的细菌纤维素(BC)为原材料制备了BC/多肽(pol)和BC/多肽/羟基磷灰石(HAp)复合材料,并利用场发射扫描电镜、X射线衍射仪和红外光谱仪对制备材料进行分析表征,采用成骨细胞评估了几种支架材料的生物相容性。结果表明,交联和仿生矿化成功地将pol和HAp引入到BC的表面和内部,细胞实验表明,3种支架材料均具有一定的生物相容性,且复合改性提高了支架材料的生物活性,制备的材料具有优异的性能,是具有应用前景的组织工程支架材料。     

图案化与生物功能化聚3,4-乙烯二氧噻吩生物界面

本工作制备了具有可调控蛋白/细胞作用且低阻抗的功能化聚3,4-乙烯二氧噻吩(PEDOT)的图案化生物界面,并在空间上引导细胞的粘附行为.功能化PEDOT共聚物由具有抗非特异性粘附的磷酸胆碱功能化的EDOT(EDOT-PC)和可进行生物耦合反应的羧基功能化的EDOT(EDOT-COOH)两种单体共聚而成.本工作研究了不同组分共聚物的电化学阻抗性能及其对蛋白、细胞的抗粘附性能,同时通过精氨酸-甘氨酸-天冬氨酸(RGD)多肽的引入实现了在抗非特异性粘附背景下对细胞的特异性粘附.在此基础上,通过光刻及电化学沉积技术制备了由细胞特异性粘附区与抗细胞粘附区组成的图案化PEDOT生物界面,可有效地在空间上控制细胞粘附行为.该工作为研究细胞在材料表面的其他行为提供了可能性,在组织修复、再生工程中有着潜在的应用价值.     

生物陶瓷支架促进再生组织血管生成和骨生成的研究进展

近年来,组织工程作为一种有前景的治疗和修复骨缺损的方法受到了广泛的关注.支架是组织工程的基本组成部分,它能够为骨组织再生提供必要的支撑和导向作用.骨组织修复过程中需要在支架内部形成一个血管网络来为细胞迁移、增殖和分化提供营养和氧气,从而实现组织再生.因此,组织工程血管化是实现骨组织再生的首要前提.生物陶瓷凭借其特殊的化学成分、高的压缩强度和优异的生物活性,成为骨再生支架的有力候选材料.然而,生物陶瓷支架在植入体内后,往往需要较长的时间才能形成血管网络.这就意味着组织内部的细胞会因长时间缺乏营养而死亡,影响组织再生效果.因此,近些年来,除研究材料成分对再生组织的血管生成和骨生成效果的影响外,研究者还从支架结构设计和支架外部的环境因素着手,以进一步提高生物陶瓷支架诱导血管生成和骨生成的能力.生物复合陶瓷不仅能提高支架的力学性能,还能改善支架的生物活性.分级多孔设计可以模拟自然骨的结构,从而更好地促进再生组织的血管化和骨生成.加载生长因子、元素掺杂和细胞植入可以为血管化提供更好的外部环境,从而更好地实现组织再生.这些因素可以协同发挥作用来促进生物陶瓷支架的血管生成和骨生成.本文从三个方面总结了影响生物陶瓷支架促进再生组织血管生成和骨生成的因素——支架材料、支架结构和支架所处的环境,并系统分析了以上因素的影响机理.最后,展望了生物陶瓷支架的发展趋势,以期为生物陶瓷的设计、加工和生物工程应用提供参考.     

可降解水凝胶作为关节软骨修复材料的研究进展

可降解水凝胶因其良好的生物相容性和生物降解性被广泛用于关节软骨的修复和再生。本文以可降解水凝胶在软骨组织工程中的三类应用策略为主线,概述了用于原位成型可注射水凝胶的蛋白多糖类材料及纳米复合类材料;系统总结了传统工艺制造组织工程支架的优缺点及多种工艺结合的制备方法;重点归纳了近年来3D打印组织工程支架从纯软骨到骨/软骨一体化、从单层到多层的研究进展;最后分析了可降解水凝胶作为关节软骨支架材料在微观定向结构和生物活性功能化方面的局限性,并作出展望：未来开展多材料、多尺度、多诱导的高仿生梯度支架是关节软骨组织工程的一个重要研究方向。     

生物医用材料表面高分子基涂层的功能化构筑

生物医用材料是为生物和医用相关领域使用而设计并制备的功能材料。随着社会的快速发展,人们对生活水平的要求相应提高,并伴随着医疗水平的不断提高和材料科学领域的高速发展,生物医用材料在人类社会生活中的应用越来越广泛。例如,在过去的几十年里,人工髋关节和膝关节植入物的数量显著增加;血管支架、心脏瓣膜、血管移植物和其他植入装置被广泛用于挽救生命和提高患者的生活质量;各种非植入的、短期使用的导管和固定螺钉等生物医用装置也在临床中广泛使用。生物医用材料作为一种人类生命和健康密切相关的功能材料,应当满足良好的生物相容性和具有一定的生物功能性,例如不会引起生理系统的严重排斥等。当生物材料与生命体例如细胞、组织、微生物等相接触时,材料的表面首当其冲,因此其在生物材料的综合性能中扮演着极为关键的角色。通过对材料表面做一定的处理或特定修饰,改变材料表面物理、化学或生物性能,就有可能在材料表面引发特殊的生物反应,促进或影响材料与生物体之间的作用,从而有可能获得促进细胞活性、组织修复或再生的功能。因此,生物材料的表面功能化研究已成为生物医用材料研究和发展的一个热点和重要领域。近年来,抗菌功能、药物负载以及细胞行为调控等功能是生物材料表面功能化构筑的重要研究方向,在材料表面构筑各种功能涂层是重要的策略之一。在抗菌涂层方面,经典的研究集中在抗黏附、接触杀菌以及释放杀菌分子的设计上,但新型的抗菌策略也不断发展,例如光热杀菌以及动态响应抑菌等。在药物负载传递方面,层层组装技术是一种被用来制备各种药物涂层的重要技术手段,组装单元的多样性为层层组装构建药物控释涂层的多样化提供了良好的基础。在细胞行为调控方面,基于层层组装的材料表面理化性能调控以及生物活性分子的固定,能够对包括黏附、铺展、迁移、增殖分化等细胞行为产生关键性的影响。本文归纳了当前生物医用材料表面功能化构筑的研究进展,分别从抗菌表面、药物负载传递、细胞行为调控等三个方面进行介绍,分析了在具体的功能化应用中生物医用材料表面面临的问题以及目前的功能化修饰方法,并展望了其应用前景,以期为制备具有更优化、更高效实际应用的生物医用材料表面提供参考。     

骨组织工程材料的研究

组织工程支架材料在组织工程中正发挥着越来越重要的作用.组织工程的核心是构建细胞生物支架材料复合体,其中,三维多孔支架材料发挥着重大作用.除了决定新生组织、器官的形状外,最重要的是为细胞提供获取营养、气体交换、废物排除的环境,为细胞增殖繁衍提供空间.因此,支架材料应是高度多孔的,支架的孔隙大小必须控制,并有严格要求.本文主要介绍了骨组织三维多孔材料的研究现状,并对组织工程支架及骨修复过程做了简要的介绍,并对其发展方向作了展望.     

组织工程支架材料研究进展

组织工程在组织或器官的修复和再生中发挥着越来越重要的作用。其中支架材料是组织工程的重要组成部分,能够为种子细胞的粘附、生长、增殖和分化等提供临时的机械支撑以及必要的生长环境,因而显得尤为重要。支架材料按照来源可以分为天然材料、人工合成材料和复合材料。从材料学的角度,介绍了骨、神经、牙齿及血管等组织工程领域中常见的支架材料的研究与应用进展,并对支架材料的发展前景进行了展望。     

体内组织工程构建小口径人工血管的研究进展

小口径血管在临床上有很大需求,但小口径血管再狭窄率很高。体内组织工程是改善小口径血管功能、实现血管再生的有效手段。介绍了小口径人工血管的国内外研究发展动态,详述了作者实验室在构建小口径人工血管方面的设计思路和研究所取得的主要进展。研究包括支架材料结构设计与制备技术,支架材料表面功能化修饰,内皮祖细胞捕捉,血管平滑肌再生,抗凝血和促内皮细胞黏附,血管再生微环境的构建等。最后对小口径人工血管研究尚需解决的科学问题和研究方向进行了讨论。     

打印技术制备高分子的移植器官

德国科学家开发出一种生物相容的可打印的高分子材料,从而可以利用三维打印技术制备移植用的器官。应用于组织工程的生物材料需要满足各种各样的要求,包括材料表面的物理化学性质、可设计性、功能化和生物相容性。此外,组织工程中的生物支架是作为模板来指导组织的生成,其内部孔隙网络和它外部几何结构都需要     

复合纳米生物医用材料的研究

生物医用材料领域中,细胞与材料间的相互作用是研究的主要课题.材料表面的微观结构对细胞的生物调控作用更为重要.纳米材料因具有一些独特的效应,如体积效应和表面效应,有利于细胞黏附、增殖和功能表达,因而作为生物医用材料特别是组织工程支架材料具有良好的应用前景.目前用于生物医用研究的纳米材料主要有无机纳米材料、高分子纳米材料以及复合纳米材料等.仿生纳米材料的研究和利用极大地促进了组织工程学的发展.本文就近年来纳米材料在生物医用材料尤其是组织工程支架材料中的应用研究现状进行了综述.     

Evaluation of cell proliferation and differentiation on a poly(propylene fumarate) 3D scaffold treated with functional peptides

Synthetic polymers were used to fabricate a three-dimensional (3D) porous scaffold of poly(propylene fumarate)/diethyl fumarate (PPF/DEF). PPF-based materials are good candidates for bone regeneration, because of their non-toxic, biodegradable byproducts, and excellent mechanical properties. However, they exhibit hydrophobic surface properties that have negative effects on cell adhesion. To change the surface properties of a PPF/DEF scaffold, the authors used three peptide modifications (RGD, cyclo RGD, and RGD-KRSR mixture) to the scaffold and tested the effects on MC3T3-E1 pre-osteoblast adhesion, proliferation, and differentiation. The results indicated that peptide modification (particularly the RGD-KRDR mixture) altered the hydrophobic surface properties of the PPF/DEF scaffold, and promoted cell adhesion. Thus, it was suggest that peptide modification is a useful method for changing the properties of the PPF/DEF scaffold surface and may be applicable in bone tissue engineering.     

Characterisation of a collagen membrane for its potential use in cardiovascular tissue engineering applications

In this study, Biomend, a collagen membrane conventionally used in the regeneration of periodontal tissue, is investigated for its possible use in the field of cardiovascular tissue engineering. A key requirement of most potential tissue engineering scaffolds is that degradation occurs in tandem with tissue regeneration and extra cellular matrix remodelling. To this end, it is crucial to understand the degradation mechanics and mechanisms of the material and to investigate the practicability of using Biomend as a possible scaffold material. With this in mind, methodologies for the initial characterisation of the scaffold material were determined. The mechanical properties of Biomend samples, subjected to various degrees of hydration and enzymatic degradation, were examined primarily through tensile testing experiments. The effects of enzymatic degradation were monitored quantitatively, by observing weight loss, and visually, by studying micrographs. Cell adhesion and viability were of primary concern. Confocal laser scanning microscopy was employed to illustrate endothelialisation on the surface of this collagen membrane. Fluorescence microscopy was used to visualise cell viability on the membrane surface. These images, coupled with assays to measure cell activity, suggest that Biomend is not a suitable substrate to allow endothelialisation. In summary, this collagen membrane has suitable mechanical properties with the potential to control its degradation rate. However, since poor endothelial cell viability was observed on the membrane, it may not be suitable for use in cardiovascular tissue engineering applications.     

PLLA–collagen and PLLA–gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA–collagen and PLLA–gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration.     

Peripheral mineralization of a 3D biodegradable tubular construct as a way to enhance guidance stabilization in spinal cord injury regeneration

Spinal cord injuries (SCI) present a major challenge to therapeutic development due to its complexity. Combinatorial approaches using biodegradable polymers that can simultaneously provide a tissue scaffold, a cell vehicle, and a reservoir for sustained drug delivery have shown very promising results. In our previous studies we have developed a novel hybrid system consisting of starch/poly-e-caprolactone (SPCL) semi-rigid tubular porous structure, based on a rapid prototyping technology, filled by a gellan gum hydrogel concentric core for the regeneration within spinal-cord injury sites. In the present work we intend to promote enhanced osteointegration on these systems by pre-mineralizing specifically the external surfaces of the SPCL tubular structures, though a biomimetic strategy, using a sodium silicate gel as nucleating agent. The idea is to create two different cell environments to promote axonal regeneration in the interior of the constructs while inducing osteogenic activity on its external surface. By using a Teflon cylinder to isolate the interior of the scaffold, it was possible to observe the formation of a bone-like poorly crystalline carbonated apatite layer continuously formed only in the external side of the tubular structure. This biomimetic layer was able to support the adhesion of Bone Marrow Mesenchymal Stem Cells, which have gone under cytoskeleton reorganization in the first hours of culture when compared to cells cultured on uncoated scaffolds. This strategy can be a useful route for locally stimulate bone tissue regeneration and facilitating early bone ingrowth.     

PLLA–collagen and PLLA–gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

Abstract

In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA–collagen and PLLA–gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration.     

Systematic studies of a self-assembling peptide nanofiber scaffold with other scaffolds

A designer self-assembling peptide nanofiber scaffold has been systematically studied with 10 commonly used scaffolds in a several week study using neural stem cells (NSC), a potential therapeutic source for cellular transplantations in nervous system injuries. These cells not only provide a good in vitro model for the development and regeneration of the nervous system, but may also be helpful in testing for cytotoxicity, cellular adhesion, and differentiation properties of biological and synthetic scaffolds used in medical practices. We tested the self-assembling peptide nanofiber scaffold with the most commonly used scaffolds for tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin in order to evaluate the utility of this surface treatment. Each scaffold was evaluated by measuring cell viability, differentiation and maturation of the differentiated stem cell progeny (i.e. progenitor cells, astrocytes, oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show high numbers of living and differentiated cells. In addition, it was demonstrated that the laminin surface treatment is capable of improving the overall scaffold performance. The designer self-assembling peptide RADA16 nanofiber scaffold represents a new class of biologically inspired material. The well-defined molecular structure with considerable potential for further functionalization and slow drug delivery makes the designer peptide scaffolds a very attractive class of biological material for a number of applications. The peptide nanofiber scaffold is comparable with the clinically approved synthetic scaffolds. The peptide scaffolds are not only pure, but also have the potential to be further designed at the molecular level, thus they promise to be useful for cell adhesion and differentiation studies as well as for future biomedical and clinical studies.     

Functionalization of poly(caprolactone) scaffolds by the surface mineralization for use in bone regeneration

The surface of a synthetic biopolymer scaffold was tailored by a mineralization with calcium phosphate for use as a functional bone tissue engineering matrix. Poly(ε-caprolactone) scaffold with a defined pore configuration constructed by a robocasting method was treated in a series of solutions involving steps of surface activation and calcium phosphate induction. The scaffold surface was completely covered with calcium phosphate nanocrystallites that had typical characteristics of bone mineral-like carbonate apatite. The scaffold with mineralized-surface demonstrated to support more favorable bone cell responses, including initial cell adhesion and proliferation and to allow higher loading of protein than the untreated-scaffold. The results suggest the developed scaffold has the potential for use as a bone regenerative matrix.     

Electrospinning of PLGA/gelatin randomly-oriented and aligned nanofibers as potential scaffold in tissue engineering

Electrospinning technique can be used to produce the three-dimensional nanofibrous scaffold similar to natural extracellular matrix, which satisfies particular requirements of tissue engineering scaffold. Randomly-oriented and aligned poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin biocomposite scaffolds were successfully produced by electrospinning in the present study. The resulting nanofibrous scaffolds exhibited smooth surface and high porous structure. Blending PLGA with gelatin enhanced the hydrophilicity but decreased the average fiber diameter and the mechanical properties of the scaffolds under the same electrospinning condition. The cell culture results showed that the elongation of the osteoblast on the aligned nanofibrous scaffold was parallel to the fiber arrangement and the cell number was similar to that of randomly-oriented scaffold, indicating that the aligned nanofibrous scaffold provide a beneficial approach for the bone regeneration.     

A Mussel‐Inspired Persistent ROS‐Scavenging,Electroactive, and Osteoinductive Scaffold Based on Electrochemical‐Driven In Situ Nanoassembly

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.     

Miniaturization of EISCAP sensor for triglyceride detection

Designing a three-dimensional (3-D) ideal scaffold has been one of the main goals in biomaterials and tissue engineering, and various mechanical techniques have been applied to fabricate biomedical scaffolds used for soft and hard tissue regeneration. Scaffolds should be biodegradable and biocompatible, provide temporary support for cell growth to allow cell adhesion, and consist of a defined structure that can be formed into customized shapes by a computer-aided design system. This versatility in preparing scaffolds gives us the opportunity to use rapid prototyping devices to fabricate polymeric scaffolds. In this study, we fabricated polycaprolactone scaffolds with interconnecting pores using a 3-D melt plotting system and compared the plotted scaffolds to those made by salt leaching. Scanning electron microscopy, a laser scanning microscope, micro-computed tomography, and dynamic mechanical analysis were used to characterize the geometry and mechanical properties of the resulting scaffolds and morphology of attached cells. The plotted scaffolds had the obvious advantage that their mechanical properties could be easily manipulated by adjusting the scaffold geometry. In addition, the plotted scaffolds provided more opportunity for cells to expand between the strands of the scaffold compared to the salt-leached scaffold.