调控细胞迁移和组织再生的生物材料研究

组织再生材料为细胞、组织的生长提供必要的物质基础,维持再生组织的形状和力学性能,并实现与周围组织的有机整合。其中,材料-细胞的相互作用是组织再生材料的核心问题。组织再生材料表界面的物理结构和化学性能可以直接影响细胞的黏附、铺展、增殖、迁移和分化等行为,进而影响组织修复和再生的效果。多数组织和器官具有立体结构,并具有更为精细的微结构。因此,三维组织再生材料体系的构建及其微结构调控是另外一个重要问题。本文结合本课题组近年的工作,综合国内外最新研究成果,重点介绍了生物材料表界面物理结构和理化性质对微粒吞噬、细胞黏附的影响、梯度材料对细胞黏附和定向迁移的作用、3D水凝胶中的细胞迁移行为及特点,以及用于皮肤和软骨组织修复与再生的植入材料,最后对生物材料在组织再生中的研究与应用进行了展望。     

基因活性皮肤再生材料研究进展

由烧伤、创伤、机械损伤等导致的皮肤缺损和功能丧失是常见的临床难题之一.皮肤再生修复涉及一系列复杂生物信号调控,通过基因治疗技术与皮肤再生材料结合,赋予皮肤再生材料更高和可控的生物活性,是实现皮肤结构和功能重建的重要策略.围绕基因活性材料在皮肤再生修复中的应用,本文首先简要介绍了皮肤缺损及其再生修复背景,分析了皮肤再生材料的主要组成和结构,然后从基因活性物质的种类、负载和释放方式等角度综述了现有基因活性皮肤再生材料的研究进展.最后,综述了基因活性化皮肤再生材料在解决血管化、瘢痕以及附属器官再生等关键问题的重要进展.     

生物材料表面性能调控骨髓间充质干细胞分化

结合细胞和生物可降解支架的组织工程和再生医学技术为组织、器官的修复和再生提供了一种新途径。骨髓间充质干细胞(BMSCs)具有多向分化潜能,因其取材简单、来源广泛、增殖能力强,无伦理争议,免疫排斥反应小而备受关注。BMSCs在特定区域定向分化成为靶细胞是干细胞治疗的一个重要前提,尤其受到生物材料表面正负电荷、亲疏水和不同的拓扑结构的影响。材料表面涂层蛋白或接枝多肽能够促进BMSCs的分化能力,而生物材料不同的机械性能、几何形状也会影响BMSCs的分化方向。本文综述了近期生物材料调控BMSCs分化的研究结果,为基于BMSCs的组织工程和再生医学材料的设计提供借鉴和指导。     

双光子聚合技术在组织工程学方面的研究进展

细胞外基质(ECM)是分布在细胞表面或细胞之间的大分子,具有复杂的网络结构,通过与细胞的相互作用调节着细胞的生长、增殖和分化,然而截止到目前这种复杂的调节作用还没有被完全理解。新兴的组织工程学通过体外构筑ECM来培养组织或器官,能够系统、深入的研究细胞与ECM之间的相互作用,进而为再生医学的发展奠定基础。双光子聚合技术具有穿透性好、空间选择性高、对生物组织损伤小等特点,是体外构筑ECM的理想方案。本文介绍了双光子吸收和双光子聚合的基本原理,梳理了水溶性双光子聚合光敏剂的研究概况,综述了光聚合水凝胶材料的研究进展并对后续研究进行了展望。     

口腔医用高分子材料的研究进展及产业转化

口腔医用材料是用于修复人体口腔颌面部缺损或缺失的软硬组织的人工合成材料或其组合物,包括修复材料本体及其修复过程中的辅助材料.目前常用的口腔材料涉及金属、陶瓷、无机物、高分子及复合物等多种类别,其中高分子材料因其多样化的结构组成而具有多种优异可控的物理化学性质,是近年来蓬勃发展的新型口腔医用材料.本文综述了高分子材料在口...     

壳聚糖基抗菌型创伤敷料的研究进展

近年来,随着再生医学的快速发展,组织工程技术再造人体组织器官被广泛的关注和研究。其中对加速创伤修复的敷料材料设计非常重要,其结构性质严重影响了再生组织的形态和效果。天然高分子壳聚糖具有广谱抗菌、强效止血作用,无毒性降解物,具有良好的生物相容性、生物活性和生物可降解性良好,能够有效地促进创面愈合和组织修复再生,在生物医用敷料领域具有广阔的应用前景。本文主要综述近年来壳聚糖基创伤敷料设计成型方法,并讨论不同的成型工艺及负载不同抗菌剂的敷料性能及用途差异。以期能够为设计和开发新型壳聚糖基抗菌型创伤敷料材料提供重要参考。     

海藻酸盐水凝胶作为递送载体在组织再生中的应用

海藻酸盐是一类存在于褐藻中的线性亲水多糖,由D-甘露糖醛酸(M)和L-古洛糖醛酸(G)以不同比例的重复单元组成.它是用于水凝胶合成的天然生物材料之一,通过简单的离子交联,即可与Ca2+等多价无机阳离子发生"蛋盒反应",形成水凝胶.海藻酸盐骨架上存在大量–OH和–COOH极性基团,通过化学或物理方法对其进行修饰,使其可以在温度、pH、光等刺激的响应下实现细胞或生物活性分子的可控释放.目前组织再生领域的主要应用策略之一是利用生物相容性材料,结合生物活性分子和细胞,以促进受损组织的再生.水凝胶材料在保护嵌入的细胞并模仿天然细胞外基质方面具有潜力.海藻酸盐也因为其易于凝胶化和良好的生物相容性,被广泛用于组织再生领域.本综述中,我们总结了用于组织再生,特别在伤口愈合、骨和心脏修复领域的海藻酸盐水凝胶的不同交联方法,重点分析了对刺激具有响应性的海藻酸盐水凝胶的特征以及其作为递送载体在组织再生中的应用.     

微纳米图案化表面对细胞行为的影响

在再生医学领域中,材料对细胞生长和组织修复的调节作用一直是极为关键的问题.随着表面图案化技术的发展,在材料表面制备规则、可控、种类多样的图案化区域成为可能,因而该技术被广泛应用于再生医学、组织工程以及细胞诊断等相关学科领域.通过微纳米表面图案化方法,改变材料的化学性质和拓扑结构,从而实现对细胞粘附、迁移、增殖、凋亡、基...     

基于可降解聚合物的纺织技术在组织工程支架中的应用

近年来,随着再生医学的发展,组织工程技术再造人体组织器官被广泛的关注和研究.其中组织工程支架对于构建组织非常重要,其结构性质严重影响着再生组织的形态和性能.本文主要针对人工可降解材料,综述近年来基于纺织技术的组织工程支架的设计成型方法,并讨论不同成型工艺的支架性能及用途的差异.在用于不同部位的组织工程支架设计中,针织、机织、编织3种纺织手段可以控制纤维集合体的三维微孔结构和力学性能,在调控细胞活性和组织再生方面有至关重要的作用,显示出不同且不可相互替代的用途.纺织技术拓宽了人工可降解高分子材料在组织工程上的应用,通过材料的选择及结构的设计能够制备出力学、生物性能满足临床使用的支架,对推动组织工程临床化进程有重要意义.     

胶原-磺化羧甲基壳聚糖/硅橡胶皮肤再生材料的制备及其对小型猪烫伤创面全层皮肤缺损的修复研究

制备了一种胶原-磺化羧甲基壳聚糖/硅橡胶皮肤再生材料,并以小型猪为模型,考察了其对烫伤全层皮肤缺损的修复性能.首先合成了磺化羧甲基壳聚糖,并对其结构进行了表征.制备了胶原-磺化羧甲基壳聚糖多孔支架,采用扫描电子显微镜(SEM)研究了磺化羧甲基壳聚糖含量对支架微结构的影响.随着磺化羧甲基壳聚糖含量的增大,胶原-磺化羧甲基壳聚糖支架从纤维结构向片状结构转化,且支架的孔径相对变大.采用体外成纤维细胞培养实验证明胶原-磺化羧甲基壳聚糖支架无明显细胞毒性.进一步将胶原-磺化羧甲基壳聚糖支架与硅橡胶膜复合,构建具有双层结构的皮肤再生材料.以小型猪为模型,评价了其对深度烫伤创面的修复性能.大体观察和组织学分析结果显示,胶原-磺化羧甲基壳聚糖/硅橡胶皮肤再生材料具有更快的血管化性能,且经该材料处理的创面能有效支持薄自体皮片的移植成活,实现深度烫伤创面的全层修复.     

DNA Nanolithography Enables a Highly Ordered Recognition Interface in a Microfluidic Chip for the Efficient Capture and Release of Circulating Tumor Cells

Microfluidic chips with nano‐scale structures have shown great potential, but the fabrication and cost issues restrict their application. Herein, we propose a conceptually new “DNA nanolithography in a microfluidic chip” by using sub‐10 nm three‐dimensional DNA structures (TDNs) as frameworks with a pendant aptamer at the top vertex (ApTDN‐Chip). The nano‐scale framework ensures that the aptamer is in a highly ordered upright orientation, avoiding the undesired orientation or crowding effects caused by conventional microfluidic interface fabrication processes. Compared with a monovalent aptamer modified chip, the capture efficiency of ApTDN‐Chip was enhanced nearly 60 % due to the highly precise dimension and rigid framework of TDNs. In addition, the scaffolds make DNase I more accessible to the aptamer with up to 83 % release efficiency and 91 % cell viability, which is fully compatible with downstream molecular analysis. Overall, this strategy provides a novel perspective on engineering nano‐scaffolds to achieve a more ordered nano‐topography of microfluidic chips.     

Spontaneous formation of radially aligned microchannels

Highly ordered radially aligned microchannels are produced on the surface of polymer nanocomposite thin films via droplet evaporation. This simple, rapid, and cost-effective approach opens a new avenue for producing macroscopic surface patterns that have potential as scaffolds or substrates in the field of microelectronics or microfluidic-based biochips.     

Formation of nematic ordered cellulose and chitin

We proposed in a previous paper a unique form of β-glucan association, nematic ordered cellulose (NOC) that is molecularly ordered, yet non-crystalline. NOC has unique characteristics; in particular, its surface properties provide with a function of tracks or scaffolds for regulated movements and fiber-production of Acetobacter xylinum [Kondo et al. 2002. Proc. Natl. Acad. Sci. USA 99: 14008–14013]. In order to extend the usage of this NOC film as a functional template, the present article attempts to clarify how β-glucan association is initiated and established by uniaxial stretching of water swollen cellulose gel films. Wide angle X-ray diffraction, high-resolution transmission electron microscopy and atomic force microscopy were employed to exhibit molecular behavior of the ordering at various scales. Then, the preparative method for NOC was applied to the other carbohydrate polymers such as α-chitin and cellulose/α-chitin blends, leading to nematic ordered states as well as cellulose. However, the method did not necessarily provide the typical structure like NOC at the molecular scale. Instead, it yielded a variety of hierarchical nematic ordered states at various scales, which allows development of new artificial ordered sheet structures.     

Bionanofabrication of metallic and semiconductor nanoparticle arrays using S-layer protein lattices with different lateral spacings and geometries

Two-dimensional (2-D) surface layer (S-layer) protein lattices isolated from the gram-positive bacterium Deinococcus radiodurans and the acidothermophilic archaeon Sulfolobus acidocaldarius were investigated and compared for their ability to biotemplate the formation of self-assembled, ordered arrays of inorganic nanoparticles (NPs). The NPs employed for these studies included citrate-capped gold NPs and various species of CdSe/ZnS core/shell quantum dots (QDs). The QD nanocrystals were functionalized with different types of thiol ligands (negative- or positive-charged/short- or long-chain length) in order to render them hydrophilic and thus water-soluble. Transmission electron microscopy, Fourier transform analyses, and pair correlation function calculations revealed that ordered nanostructured arrays with a range of spacings (approximately 7-22 nm) and different geometrical arrangements could be fabricated through the use of the two types of S-layers. These results demonstrate that it is possible to exploit the physicochemical/structural diversity of prokaryotic S-layer scaffolds to vary the morphological patterning of nanoscale metallic and semiconductor NP arrays.     

Three‐Dimensional Scaffolds of Carbonized Polyacrylonitrile for Bone Tissue Regeneration

Carbon‐based materials have been extensively studied for stem cell culture. However, difficulties associated with engineering pure carbon materials into 3D scaffolds have hampered applications in tissue engineering and regenerative medicine. Carbonized polyacrylonitrile (cPAN) could be a promising alternative, as cPAN is a highly ordered carbon isomorph that resembles the graphitic structure and can be easily processed into 3D scaffolds. Despite the notable features of cPAN, application of cPAN in tissue engineering and regenerative medicine have not been explored. This study, for the first time, demonstrates the fabrication of microporous 3D scaffolds of cPAN and excellent osteoinductivity of cPAN, suggesting utility of 3D cPAN scaffolds as synthetic bone graft materials. The combination of excellent processability and unique bioactive properties of cPAN may lead to future applications in orthopedic regenerative medicine.     

Cellulose nanocrystals as biobased nucleation agents in poly-l-lactide scaffold: Crystallization behavior and mechanical properties

The mechanical strength of polymer scaffold is closely related to its crystallinity. In this work, cellulose nanocrystals (CNC) were incorporated into poly-l-lactide (PLLA) scaffold which was fabricated by selective laser sintering, aiming to improve the mechanical properties. CNC possesses numerous hydroxyl groups which might form hydrogen bond with PLLA molecular chains. The hydrogen bond induces the ordered arrangement of PLLA chain by using CNC as heterogeneous nucleating agent, thereby increasing crystallization rate and crystallinity. Results showed that PLLA scaffolds with 3 wt% CNC resulted in 191%, 351%, 34%, 83.5%, 56% increase in compressive strength, compressive modulus, tensile strength, tensile modulus and Vickers hardness, respectively. Encouragingly, with the incorporation of hydrophilic CNC, the PLLA/CNC scaffolds showed not only better hydrophilicity, but also faster degradation than PLLA. In vitro cell culture studies proved that the PLLA/CNC scaffolds were biocompatible and capable of supporting cell adhesion, proliferation and differentiation. The above results indicated that the PLLA/CNC scaffolds may therefore be a potential replacement in bone repair.     

The stepwise supramolecular organisation of guanosine derivatives

Several supramolecular architectures generated by guanosine derivatives are described. The research started from the fortuitous observation of a lyotropic behavior exhibited by a guanylic nucleotide in water. This observation stimulated extensive research on several natural and lipophilic guanosine derivatives which self-assemble in different architectures (discs, ribbons, helices...), according to their structure and environment. These ordered structures can be used as scaffolds for photo- or electro-active moieties and for the fabrication of molecular electronic devices.     

Design Parameters of Tissue‐Engineering Scaffolds at the Atomic Scale

Stem‐cell behavior is regulated by the material properties of the surrounding extracellular matrix, which has important implications for the design of tissue‐engineering scaffolds. However, our understanding of the material properties of stem‐cell scaffolds is limited to nanoscopic‐to‐macroscopic length scales. Herein, a solid‐state NMR approach is presented that provides atomic‐scale information on complex stem‐cell substrates at near physiological conditions and at natural isotope abundance. Using self‐assembled peptidic scaffolds designed for nervous‐tissue regeneration, we show at atomic scale how scaffold‐assembly degree, mechanics, and homogeneity correlate with favorable stem cell behavior. Integration of solid‐state NMR data with molecular dynamics simulations reveals a highly ordered fibrillar structure as the most favorable stem‐cell scaffold. This could improve the design of tissue‐engineering scaffolds and other self‐assembled biomaterials.     

Block copolymers as nanoscopic templates

Block copolymers self‐assemble into well‐ordered, microphase separated morphologies having dimensions on the molecular scale. The key to the use of these nanoscopic structures lies in controlling the spatial orientation of the morphology, particularly in thin films. The preferential interactions of the segments of the blocks with interfaces forces an alignment of the morphology parallel to the interface. Here we describe the use of controlled interfacial interactions and electric fields to manipulate the orientation of the morphology and subsequent steps towards the generation of nanoporous templates as scaffolds for nanoscopic structures.     

Two-dimensional scaffolds for the parallel alignment of rod-shaped conjugated molecules

Described is a method for creating two-dimensional, ordered arrays of linear, conjugated organic molecules on polyimide scaffolds. Key to the design was the enforcement of consecutive 90 degrees twist angles along the polyimide backbone. Rod molecules that are templated by such scaffolds are held parallel and in the same plane and have optical properties that are similar to those of monomeric analogues. As supporting evidence for the structures of the polymers, a series of model compounds were synthesized and characterized by X-ray crystallography. The polymeric materials are soluble and have been characterized by 1H NMR, 13C NMR, MALDI-TOF, and UV-vis spectroscopy.