智能水凝胶在组织工程中的应用

背景：与传统水凝胶相比,智能水凝胶能够对外界刺激诸如温度、pH值、光、磁场等作出不同的应答表现,产生二级结构甚至化学结构的变化,自发组装形成有序的超分子结构,最终形成具有三维结构的凝胶。 目的：综述智能水凝胶的研究现状及其在组织工程的应用。 方法：应用计算机检索中国知网及PubMed 数据库从建库至2014年有关智能水凝胶在组织工程中应用的文献,检索关键词为“水凝胶,组织工程学,hydrogel,Tissue engineering”。 结果与结论：智能水凝胶中包括温度敏感性、pH敏感性、光敏感性、磁敏感性及温度/pH双重敏感性水凝胶,其对于外界环境变化能自动感知并能作出响应性的反应,在药物递送系统、药物释放,修复和改善缺损组织等领域表现出一系列传统材料所没有的突出性能,尤其是在组织工程方面表现出相当的优越性：低免疫原性,减少了炎症和排斥作用;具备生物可降解性;能真正在三维尺度上模拟细胞所处微环境,从而利于细胞黏附、生长、迁移及分化等。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

水凝胶材料和间充质干细胞在组织工程中的应用进展

随着组织工程学的发展, 人们越来越关注将水凝胶作为支架材料并与细胞3D培养相结合用于组织器官再生与修复。水凝胶由亲水性聚合物、共聚物或可以形成大分子链的单体大分子交联而成, 可吸收大量水分并保持3D结构, 具有良好的生物相容性、可包埋细胞和有效的递送生物活性分子等特点, 因而被广泛用于生物医药领域的药物输送和组织工程等领域。间充质干细胞可以从骨髓、脂肪、脐带等多种组织中获取, 具有低免疫原性及多向分化潜能, 是细胞3D培养以及细胞治疗的首选。目前间充质干细胞主要是2D培养模式, 该培养模式下的间充质干细胞繁殖率低, 且无法模拟体内的生长环境。水凝胶材料作为3D细胞培养支架具有良好的相容性, 可以模拟体内的生长环境, 在修复受损软骨、骨、皮肤和心脏等组织中有巨大潜力。概述水凝胶、间充质干细胞以及间充质干细胞和水凝胶材料在组织工程中的应用, 展示水凝胶材料与间充质干细胞的3D培养在不同组织再生和修复中的发展趋势和可能性, 以期为后续水凝胶和干细胞的深入应用研究提供参考。     

胶原水凝胶在软骨与骨组织工程中的研究进展

胶原水凝胶因其具有优良的生物相容性、生物力学性能，在软骨与骨组织工程、生物填充材料、创伤修复、药物缓释和细胞培养等医学领域获得广泛的关注和应用。本文重点介绍了胶原水凝胶在软骨与骨组织工程方面的研究进展，详细阐述了胶原水凝胶的性能、交联方法和类型，并对胶原水凝胶在软骨与骨组织工程中的研究现状进行了讨论，对其应用前景进行了展望。     

组织工程生物绷带及敷料在创伤修复领域中的应用

背景：医用敷料作为伤口处的覆盖物,在伤口愈合过程中,可以替代受损的皮肤起到暂时性屏障作用,避免或控制伤口感染,提供有利于创面愈合的环境。如何既能快速固定、有效止血,又可以减轻或避免止血后对伤肢血循环造成的不利影响,加快伤口愈合、减轻伤痛是创伤急救医学亟待解决的难题。 目的：文章综述了医用生物敷料在创伤修复领域中的应用现状及研究进展,揭示其发展前景,为其在创伤修复过程中的应用提供理论基础。 方法：应用计算机检索CNKI和PubMed数据库中1998-01/2008-12关于医用生物敷料的文章,在标题和摘要中以“医用敷料;生物材料,壳聚糖,水凝胶,组织工程”或“medical dressing,chitosan”为检索词进行检索。选择文章内容与创伤修复相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到146篇文献,中文107篇,英文39篇,根据纳入标准选择38篇文章进行综述。 结果与结论：就目前临床使用及研究的医用敷料,根据其所用的材料将其分成了天然材料和合成高分子,无机材料和复合材料,并对敷料类产品质量控制中出现的问题进行了讨论,展望了敷料类产品的未来发展方向。为医用敷料类产品的研发提供理论依据。     

高分子纳米纤维在组织工程支架材料研究中的应用

介绍了高分子纳米纤维的特点、合成方法、生物相容性以及表明修饰,阐明其作为新型支架材料在骨组织工程中的应用价值。     

近红外光响应水凝胶在组织工程领域的应用

背景：近红外光响应水凝胶具有高度时空精准性、远程可调性及安全无创性等多种优异特性,为组织工程的发展提供了新的探索方向。目的：总结近年来近红外光响应水凝胶在组织工程领域的应用进展。方法：利用计算机检索中国知网及PubMed数据库相关文献,中文检索词为“近红外光响应水凝胶、组织工程、骨缺损、骨修复、骨再生、伤口愈合、伤口敷料、血管生成”,英文检索词为“near infrared responsive hydrogels,tissue engineering,bone defect,bone repair,bone regeneration,wound healing,wound dressing,angiogenesis”,检索时限为2006年5月至2022年10月,部分经典文献延长检索时间限制,分析所得文献的摘要及内容,通过纳入和排除标准得到相关文献,最终纳入97篇符合标准的文献进行综述。结果与结论：(1)近红外光响应材料通过控制感染减轻炎症、促进血管生成、促进成骨细胞分化和新骨形成等过程参与组织修复。(2)近红外光响应材料可以通过构建具有光热效应的热敏水凝胶或者利用光化学反应制备近红外...     

组织工程支架在神经修复中的应用

背景：组织工程支架能够营造适当的神经再生微环境,富集神经再生所需的营养因子,促进轴突生长。 目的：综述近年来组织工程材料在神经损伤修复方面的科研进展。 方法：应用计算机检索PubMed数据库2009至2014年关于组织工程材料修复神经损伤的文章,检索词为“nerve regeneration, prostheses and implants”,并限定为“Full text”。同时利用计算机检索中国知网数据库2004至2014年相关方面的文章,检索词为“神经修复,材料”。 结果与结论：目前用于神经损伤的支架材料主要有天然材料、天然衍生材料、合成材料与复合材料,不同种材料具备各自的优点与缺点。通过化学交联剂或化学修饰,将天然衍生聚合物与其他天然或合成材料复合,可提高其理化和生物学特性,即复合材料神经支架取得的神经再生效果比单一材料效果好,因此当前的研究热点是复合材料。在临床研究方面,胶原蛋白基的神经修复支架材料已开始进入临床研究阶段。 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

应用天然水凝胶修复关节软骨损伤的研究进展

由创伤或骨关节炎造成的软骨损伤是常见的关节疾病类型,是现代社会严重的经济负担,对患者造成极大的痛苦。因为软骨中无神经、血管和淋巴组织,且软骨细胞迁移能力差,祖细胞数量少,导致软骨缺损的自愈能力受到很大限制。水凝胶具有诸多特性,如高吸水性能、生物降解性、可控的孔隙率及生物相容性,具有用作关节软骨替代物所需的仿生性能,已发展成为材料科学中适合应用于软骨再生的支架生物材料之一。本综述总结了用于关节软骨修复水凝胶及动物模型。由于受当前技术的局限,人们仍然难以克服诸如血管生成和机械性能不足等问题,本综述的主要目的是回顾应用天然水凝胶用于软骨损伤的进展,希望为临床治疗关节软骨损伤提供新的思路。     

智能型水凝胶在生物医学工程中的应用

介绍了不同响应的智能型水凝胶的类型，同时综述了在医药控制释放材料、组织填充材料、人工玻璃体、人工软骨、医用敷料、医用崩解剂、角膜接触镜材料、组织培养及临床诊断方面的应用。     

纳米复合水凝胶在骨组织工程中的应用

文题释义：纳米颗粒：是指纳米量级的微观颗粒,指至少在一个维度上小于100 nm的颗粒。纳米颗粒具有较大的比表面积,可以与水凝胶结构链形成紧密的界面,改善水凝胶的机械性能。纳米复合水凝胶：水凝胶与纳米颗粒化学或物理交联的有机-无机或有机-有机网络结构。由于水凝胶网络与纳米颗粒的相互作用,纳米复合水凝胶具有增强的化学、物理或生物特性。 背景：纳米复合水凝胶是具有良好生物相容性和骨传导性能的仿生材料,在骨组织工程中广泛应用。 目的：总结纳米颗粒的分类及纳米复合水凝胶在骨组织工程中的应用。 方法：应用计算机对CNKI数据库、PubMed数据库、Web of Science数据库2000至2019年发表的文献进行检索,中文检索关键词为“纳米复合材料,骨组织工程,纳米颗粒,水凝胶”,英文检索关键词为“Nanocomposites;Bone Tissue Engineering;Nanoparticle;Hydrogels”。根据纳入和排除标准最终纳入69篇文献进行结果分析。结果与结论：①目前常作为纳米填料的纳米颗粒主要有碳基纳米颗粒、金属和金属氧化物纳米颗粒、聚合物纳米颗粒、磷酸钙基纳米颗粒;②纳米颗粒与水凝胶的复合能改善水凝胶的机械性能;③纳米复合水凝胶能促进种子细胞的黏附和成骨分化,从而应用于骨组织工程;④目前,纳米复合水凝胶在骨组织工程中的应用还存在纳米颗粒分散性差、骨组织工程中的血管化能力弱及材料降解速率难以调控等问题。 ORCID: 0000-0002-1900-9641(林开利) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Microengineered hydrogels for tissue engineering

Hydrogels have been extensively used in various biomedical applications such as drug delivery and biosensing. More recently the ability to engineer the size and shape of biologically relevant hydrogels has generated new opportunities in addressing challenges in tissue engineering such as vascularization, tissue architecture and cell seeding. Here, we discuss the use of microengineered hydrogels for tissue engineering applications. We will initially provide an overview of the various approaches that can be used to synthesize hydrogels with controlled features and will subsequently discuss the emerging applications of these hydrogels.     

Photopolymerizable hydrogels for tissue engineering applications

Photopolymerized hydrogels are being investigated for a number of tissue engineering applications because of the ability to form these materials in situ in a minimally invasive manner such as by injection. In addition, hydrogels, three-dimensional networks of hydrophilic polymers that are able to swell large amounts of water, can be made to resemble the physical characteristics of soft tissues. Hydrogel materials also generally exhibit high permeability and good biocompatibility making, these materials attractive for use in cell encapsulation and tissue engineering applications. A number of hydrogel materials can be formed via photopolymerization processes mild enough to be carried out in the presence of living cells. This allows one to homogeneously seed cells throughout the scaffold material and to form hydrogels in situ. This review presents advantages of photopolymerization of hydrogels and describes the photoinitiators and materials in current use. Applications of photopolymerized hydrogels in tissue engineering that have been investigated are summarized.     

Photo-patterning of porous hydrogels for tissue engineering

Since pore size and geometry strongly impact cell behavior and in vivo reaction, the ability to create scaffolds with a wide range of pore geometries that can be tailored to suit a particular cell type addresses a key need in tissue engineering. In this contribution, we describe a novel and simple technique to design porous, degradable poly(2-hydroxyethyl methacrylate) hydrogel scaffolds with well-defined architectures using a unique photolithography process and optimized polymer chemistry. A sphere-template was used to produce a highly uniform, monodisperse porous structure. To create a patterned and porous hydrogel scaffold, a photomask and initiating light were employed. Open, vertical channels ranging in size from 360+/-25 to 730+/-70 microm were patterned into approximately 700 microm thick hydrogels with pore diameters of 62+/-8 or 147+/-15 microm. Collagen type I was immobilized onto the scaffolds to facilitate cell adhesion. To assess the potential of these novel scaffolds for tissue engineering, a skeletal myoblast cell line (C2C12) was seeded onto scaffolds with 147 microm pores and 730 microm diameter channels, and analyzed by histology and digital volumetric imaging. Cell elongation, cell spreading and fibrillar formation were observed on these novel scaffolds. In summary, 3D architectures can be patterned into porous hydrogels in one step to create a wide range of tissue engineering scaffolds that may be tailored for specific applications.     

Injectable chitosan-based hydrogels for cartilage tissue engineering

Water-soluble chitosan derivatives, chitosan-graft-glycolic acid (GA) and phloretic acid (PA) (CH-GA/PA), were designed to obtain biodegradable injectable chitosan hydrogels through enzymatic crosslinking with horseradish peroxidase (HRP) and H₂O₂. CH-GA/PA polymers were synthesized by first conjugating glycolic acid (GA) to native chitosan to render the polymer soluble at pH 7.4, and subsequent modification with phloretic acid (PA). The CH-GA43/PA10 with a degree of substitution (DS, defined as the number of substituted NH₂ groups per 100 glucopyranose rings of chitosan) of GA of 43 and DS of PA of 10 showed a good solubility at pH values up to 10. Short gelation times (e.g. 10 s at a polymer concentration of 3 wt%), as recorded by the vial tilting method, were observed for the CH-GA43/PA10 hydrogels using HRP and H₂O₂. It was shown that these hydrogels can be readily degraded by lysozyme. In vitro culturing of chondrocytes in CH-GA43/PA10 hydrogels revealed that after 2 weeks the cells were viable and retained their round shape. These features indicate that CH-GA/PA hydrogels are promising as an artificial extracellular matrix for cartilage tissue engineering.     

Bioresponsive phosphoester hydrogels for bone tissue engineering

Bioresponsive and intelligent biomaterials are a vehicle for manipulating cell function to promote tissue development and/or tissue engineering. A photopolymerized hydrogel based on a phosphoester- poly(ethylene glycol) polymer (PhosPEG) was synthesized for application to marrow-derived mesenchymal stem cell (MSC) encapsulation and tissue engineering of bone. The phosphor-containing hydrogels were hydrolytically degradable and the rate of degradation increased in the presence of a bone-derived enzyme, alkaline phosphatase. Gene expression and protein analysis of encapsulated MSCs demonstrated that PhosPEG-PEG cogels containing an intermediate concentration of phosphorus promoted the gene expression of bone-specific markers including type I collagen, alkaline phosphatase, and osteonectin, without the addition of growth factors or other biological agents, compared with pure poly(ethylene glycol)-based gels. Secretion of alkaline phosphatase, osteocalcin, and osteonectin protein was also increased in the PhosPEG cogels. Mineralization of gels increased in the presence of phosphorus in both cellular and acellular constructs compared with PEG gels. In summary, phosphate-PEG-derived hydrogels increase gene expression of bone-specific markers, secretion of bone-related matrix, and mineralization and may have a potential impact on bone-engineering therapies.     

Neural tissue engineering of the CNS using hydrogels

Current therapies have limited capacity to curtail disease progression or damage of the central nervous system (CNS) of adult mammals and successful regeneration following injury or disease does not occur. Regeneration of the CNS is limited by physical and chemical inhibitory barriers within the injured environment and the absence of positive cues that elicit and guide repair. Neural tissue engineering strategies focus on developing scaffolds that artificially generate favourable cellular microenvironments that attempt to tip the balance in favour of regeneration. Some recent advances using scaffolds to promote regeneration within the CNS, particularly in conjunction with stem cells, has generated promising results. This review focuses on hydrogel scaffolds which have been used extensively in neural tissue engineering applications and addresses the physical and chemical modifications of these materials to promote nerve regeneration.     

Injectable alginate hydrogels for cell delivery in tissue engineering

Alginate hydrogels are extremely versatile and adaptable biomaterials, with great potential for use in biomedical applications. Their extracellular matrix-like features have been key factors for their choice as vehicles for cell delivery strategies aimed at tissue regeneration. A variety of strategies to decorate them with biofunctional moieties and to modulate their biophysical properties have been developed recently, which further allow their tailoring to the desired application. Additionally, their potential use as injectable materials offers several advantages over preformed scaffold-based approaches, namely: easy incorporation of therapeutic agents, such as cells, under mild conditions; minimally invasive local delivery; and high contourability, which is essential for filling in irregular defects. Alginate hydrogels have already been explored as cell delivery systems to enhance regeneration in different tissues and organs. Here, the in vitro and in vivo potential of injectable alginate hydrogels to deliver cells in a targeted fashion is reviewed. In each example, the selected crosslinking approach, the cell type, the target tissue and the main findings of the study are highlighted.     

Cell encapsulation in biodegradable hydrogels for tissue engineering applications

Encapsulating cells in biodegradable hydrogels offers numerous attractive features for tissue engineering, including ease of handling, a highly hydrated tissue-like environment for cell and tissue growth, and the ability to form in vivo. Many properties important to the design of a hydrogel scaffold, such as swelling, mechanical properties, degradation, and diffusion, are closely linked to the crosslinked structure of the hydrogel, which is controlled through a variety of different processing conditions. Degradation may be tuned by incorporating hydrolytically or enzymatically labile segments into the hydrogel or by using natural biopolymers that are susceptible to enzymatic degradation. Because cells are present during the gelation process, the number of suitable chemistries and formulations are limited. In this review, we describe important considerations for designing biodegradable hydrogels for cell encapsulation and highlight recent advances in material design and their applications in tissue engineering.