光交联水凝胶材料的研究与生物医学应用进展

光交联制备水凝胶技术具有非物理接触以及时空精确可控等优势,在细胞3D培养/打印以及组织工程和再生医学领域具有广阔的应用前景.当前,光交联水凝胶的制备主要基于光引发自由基交联反应、光点击交联反应或光偶联交联反应.本文分别介绍了以上交联反应各自的技术发展史、应用现状以及相关的优势和技术瓶颈.还着重介绍了本课题组在光交联水凝胶领域开展的研究与转化工作,主要包括提出了利用光笼分子的光剪切释放活性基团触发偶联交联的非自由基光交联策略,即光偶联反应交联策略.该策略实现了光交联水凝胶的低毒、可控构筑,同时赋予了光交联水凝胶技术的原位组织黏附特性,为该技术的最终临床转化奠定了基础.     

酶促水凝胶的合成及生物传感应用研究进展

近年来,聚合物基水凝胶材料已经成为一种独特的修饰材料,为新型生物传感器的设计提供了新思路.酶具有特异性高、毒性低、催化效率高等良好特性,已被用于催化聚合各种新型水凝胶.本文综述了几种酶促水凝胶的合成方法及其在细胞代谢物、组织工程、伤口愈合和癌症监测等方面的潜在应用,并对基于酶促水凝胶反应的生物传感器的制备与应用进行了总结与展望.     

光控水凝胶的构筑及在生物医药领域的应用

水凝胶由于具有优越的保水性、良好的生物相容性和可降解性,被认为是最接近人体组织的生物医用材料。通过构建环境敏感水凝胶可以高度拟合生物组织的微环境,实现其在组织工程与再生医学领域的应用。由于光具有非物理接触和时空分辨等优势,利用光调控技术可实现水凝胶微环境的精确构筑与调控。本文重点介绍了近年来光控水凝胶的构筑,以及在生物医学和材料领域的应用进展。     

仿贻贝水凝胶在组织愈合中的应用研究

手术线缝合和订皮钉固定是外科手术中修复组织损伤的常规方法,但是对于相对脆弱的软组织,使用组织粘合剂是代替常规组织修复的重要方法之一.尽管合成的组织粘合剂已经得到广泛应用,但是仍然存在一些缺点,例如湿润环境中粘合性差和潜在毒性等.纤维蛋白胶具有良好的止血性能,但是存在拉伸性和粘附性差、价格昂贵等缺点.仿生粘合剂作为组织粘附剂、止血剂或密封剂在临床手术中应用广泛.然而,在组织创伤的修复应用中,发展耐水粘附、具有生物相容性,多功能一体化的医用粘合剂是近年来研究的热点和难点.自从Messersmith课题组报道了受贻贝启发的多功能聚多巴胺涂层以来,含有酚羟基的材料由于其抗氧化、抗菌消炎等功效,被广泛地应用于医学、食品、化妆品和水处理等领域.仿贻贝水凝胶具有优异的组织粘附性、止血抑菌性、生物安全性和可塑性,是理想的医用粘合剂材料.概述了多酚-合成高分子水凝胶、多酚-生物大分子水凝胶、多酚-无机纳米材料复合水凝胶以及聚多巴胺纳米颗粒复合水凝胶在组织粘附、止血抑菌等方面的研究进展和在组织愈合中的应用探索.总结了多酚水凝胶作为医用组织粘附剂、止血剂、密封剂仍需解决的关键问题,并对此领域的发展趋势进行了展望,有助于推动仿贻贝水凝胶作为新兴生物粘合剂在医学领域中的应用.     

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.     

纤维素基智能凝胶的制备、结构及性能研究

纤维素是自然界中最丰富的生物质资源,因其具有可再生性、生物相容性、无毒、可降解等诸多特性,纤维素及其衍生物不仅广泛应用于传统的工业领域,而且在药物控释、组织工程、可穿戴设备材料等领域也有着广阔的应用前景。受到工程技术应用需求的驱动,以纤维素及其衍生物为基材的智能凝胶材料已成为目前的研究热点。作者系统研究了纤维素基智能凝胶材料的制备、结构及性能。主要内容如下： 1.制备了纤维素基气凝胶并对其进行疏水改性,研究了疏水改性后的纤维素气凝胶材料在水下吸附气体的能力,并设计了纤维素基智能捕集器,用于连续不断地吸附从海底释放的甲烷气体。 2.制备了TEMPO氧化的纳米纤维素纤维,并将其用于增强聚丙烯酰胺/明胶形状记忆水凝胶的力学性能;制备的复合水凝胶展示了较好的形状记忆行为,并且该水凝胶的形状记忆性能具有较好的可重复性。 3.利用羧甲基纤维素制备了对多种金属阳离子响应的形状记忆水凝胶;能够通过改变羧甲基纤维素与金属离子之间的交联密度,调节该水凝胶的力学性能。 4.将羧甲基纤维素钠与聚丙烯酸（PAA）复合制备出具有较优异机械性能和自修复性能的聚丙烯酸/羧甲基纤维素钠水凝胶。通过简单的浸泡法,将该复合水凝胶浸泡在氯化钠（NaCl）溶液中,可以促进CMC和PAA之间的链缠结,进一步提升其机械性能。此外,由于水凝胶的导离子性,制备的水凝胶具有良好的传导性能,有望实现在电子皮肤或可穿戴设备中的应用。     

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。     

γ-聚谷氨酸/壳聚糖/纳米银复合水凝胶的制备和表征

为解决创伤修复过程中致病菌引起的感染问题,本研究制备了γ-聚谷氨酸/壳聚糖/纳米银复合水凝胶,对复合材料进行结构性能、物理性能、细胞毒性和抗菌性评价。透射电子显微镜结果表明,材料上合成粒径1~9nm的纳米银粒子;扫描电子显微镜观察到材料呈三维网状结构,傅里叶红外光谱表明,原位合成纳米银的化学反应不影响水凝胶的化学结构;热失重分析表明,材料具有良好的热稳定性且可以通过调整反应物剂量调控纳米银在水凝胶上的负载量;细胞毒性实验和抗感染实验证明复合水凝胶具有良好的细胞相容性和抗菌性。本研究为实现基于纳米银的抗菌性创伤修复材料的应用奠定实验基础。     

PNIPAM温敏微凝胶在生物医学领域中的应用研究

水凝胶因其良好的生物相容性及环境刺激响应性而在生物医学领域有着广泛的用途,但仍存在机械强度差、响应速度慢、不能生物降解等缺点。针对这些问题,特别是宏观水凝胶响应慢的问题,我们近年来以具有温度敏感性的聚N-异丙基丙烯酰胺(PNIPAM)微凝胶为基础,设计制备了一系列生物材料,分别应用于药物控释、生物传感以及组织工程等生物医学领域。我们设计制备了具有良好葡萄糖敏感性的PNIPAM微凝胶,实现了可自我调控的胰岛素可控释放。以PNIPAM微凝胶为基础,提出了新的聚合胶态晶体阵列光学传感方法,设计制备了多种可快速响应的新型生物光学传感器。实现了PNIPAM微凝胶的实时凝胶化,并将其发展成为一种新型的可注射细胞支架材料。进一步利用该体系的可逆性,提出了制备在药物筛选、肿瘤研究以及组织工程等领域有重要用途的多细胞球的新方法。     

可拉伸超韧水凝胶的制备和应用

综述了可拉伸超韧水凝胶的设计原理及其在组织工程和柔性电子器件领域的应用. 通过将网络结构层次、 化学结构、 增韧机制与宏观力学性能相结合, 重点讨论了单网络水凝胶、 双网络水凝胶、 纳米复合水凝胶及其它水凝胶等可拉伸超韧水凝胶的研究进展, 并总结和展望了新思路和新方向.     

In situ photocrosslinkable hyaluronic acid‐based surgical glue with tunable mechanical properties and high adhesive strength

Hyaluronic acid (HA), a naturally occurring linear polysaccharide, has been widely used as a key biomaterial in a range of cosmetic and therapeutic applications. Its excellent biocompatibility and bio‐functions related to tissue regeneration encourage the development of HA‐based hydrogels to expand its applications. This study details an in situ forming surgical glue based on photocrosslinkable HA, providing tunable mechanical properties and firm tissue adhesion under wet and dynamic conditions. Depending on the degree of photocrosslinkable methacrylate groups in HA polymer chains, the mechanical properties of hyaluronate methacrylate (HAMA) hydrogels prepared by UV photocrosslinking was improved. Ex vivo adhesion tests revealed that HAMA hydrogels exhibited 3‐fold higher shear adhesive strength compared to gelatin methacryloyl hydrogels and achieved firm adherence to the porcine skin tissue for several weeks. The high adhesive strength of HAMA hydrogels, under dry and wet conditions, suggests that it may have great promise as a tissue adhesive. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 522–530     

Photocrosslinkable chitosan hydrogels and their biomedical applications

Chitosan is a bioactive macromolecule with a wide variety of applications due to its excellent biological properties such as biodegradability, biocompatibility, and antibacterial activity, and so forth. This highlight focuses on the preparation of photoactive chitosans, the formation of photocrosslinkable chitosan hydrogels, and the related photopolymerization mechanisms. Moreover, the great potential applications of photocrosslinkable chitosan hydrogels for human tissues are also discussed. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1862–1871     

Current research progress of photopolymerized hydrogels in tissue engineering

Owing to the special fo rmation of photopolymerized hydrogels,they can effectively control the formation of hydrogels in space and time.Moreover,the photopolymerized hydrogels have mild formation conditions and biocompatibility;therefore,they can be widely used in tissue engineering.With the development and application of manufacturing technology,photopolymerized hydrogels can be widely used in cell encapsulation,scaffold materials,and other tissue engineering fields through more elaborate manufacturing methods.This review covers the types of photoinitiators,manu facturing technologies for photopolymerized hydrogels as well as the materials used,and a summary of the applications of photopolymerized hydrogels in tissue engineering.     

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Supramolecular hydrogels are a class of self‐assembled network structures formed via non‐covalent interactions of the hydrogelators. These hydrogels capable of responding to external stimuli are considered to be smart materials due to their ability to undergo sol–gel and/or gel–sol transition upon subtle changes in their surroundings. Such stimuli‐responsive hydrogels are intriguing biomaterials with applications in tissue engineering, delivery of cells and drugs, modulating tissue environment to promote innate tissue repair, and imaging for medical diagnostics among others. This review summarizes the recent developments in stimuli‐responsive supramolecular hydrogels and their potential applications in regenerative medicine. Specifically, various structural aspects of supramolecular hydrogelators involved in self‐assembly, the role of external stimuli in tuning/controlling their phase transitions, and how these functions could be harnessed to advance applications in regenerative medicine are focused on. Finally, the key challenges and future prospects for these versatile materials are briefly described.     

Photo-crosslinkable hydrogel and its biological applications

In the past few years,photo-crosslinkable hydrogels have drawn a great attention in tissue engineering applications due to their high biocompatibility and extracellular matrix(ECM)-like structure.They can be easily biofabricated through exposure of a photosensitive system composed of photo-crosslinkable hydrogels,photo-initiators and other compounds such as cells and therapeutic molecules,to ultraviolet or visible light.With the development of biofabrication methods,ma ny resea rchers studied the biological applications of photo-crosslinkable hydrogels in tissue engineering,such as vascular,wound dressing and bone engineering.This review highlights the biomaterials for photo-crosslinkable hydrogels,bio fabrication techniques and their biological applications in tissue engineering.Meanwhile,the challenges and prospects of photo-crosslinkable hydrogels are discussed as well.     

Personalized hydrogels for individual health care: preparation,features, and applications in tissue engineering

Biomaterials-based tissue engineering scaffolds play an essential role as an independent therapy or with the combination of cellular or biological active constituents in tissue regeneration applications. However, synthetic grafts, xenografts, and allografts are recognized as foreign materials in human body, resulting in suboptimal clinical outcomes. Recently, autologous materials from a patient's body have drawn great attention in clinical treatment and tissue engineering. Moreover, the autologous scaffolds equipped with the advantages of tissue-like hydrogels have great potential to become a highly versatile tool as personalized hydrogels (PHs) for applications in 3D cell culture and tissue engineering. PHs may feature excellent biocompatibility, tailorable mechanical properties, regenerative capability, non-rejection of grafts/transplants on immunological responses, and customizable properties which could be suitable to meet the personal and clinical care. Here, we present a scoping review of recent progress of PHs with a focus on detailed preparation methods, material properties, and tissue engineering applications along with their challenges and opportunities. It is expected that PHs will circumvent the limitations of current tissue engineering therapies and will be used as next-generation scaffolds for tissue engineering and translational research.     

Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering

Microfluidic technologies are emerging as an enabling tool for various applications in tissue engineering and cell biology. One emerging use of microfluidic systems is the generation of shape-controlled hydrogels (i.e., microfibers, microparticles, and hydrogel building blocks) for various biological applications. Furthermore, the microfluidic fabrication of cell-laden hydrogels is of great benefit for creating artificial scaffolds. In this paper, we review the current development of microfluidic-based fabrication techniques for the creation of fibers, particles, and cell-laden hydrogels. We also highlight their emerging applications in tissue engineering and regenerative medicine.     

高分子水凝胶在医学领域的研究进展

高分子水凝胶是具有三维网络结构的一种新型材料,吸水溶胀后质地柔软,与生物体组织相似,生物相容性和生物可降解性良好,具有一定的力学性能,因此在医学领域具有重要的应用。本文对高分子水凝胶在医学领域的研究热点进行了归纳总结,并重点阐述了高分子水凝胶在药物输送、组织工程支架、伤口敷料和生物传感器等医学领域应用的最新研究进展,并对其未来发展趋势进行了展望。     

The rheological and structural properties of Fmoc-peptide-based hydrogels: the effect of aromatic molecular architecture on self-assembly and physical characteristics

Biocompatible hydrogels are of high interest as a class of biomaterials for tissue engineering, regenerative medicine, and controlled drug delivery. These materials offer three-dimensional scaffolds to support the growth of cells and development of hierarchical tissue structures. Fmoc-peptides were previously demonstrated as attractive building blocks for biocompatible hydrogels. Here, we further investigate the biophysical properties of Fmoc-peptide-based hydrogels for medical applications. We describe the structural and thermal properties of these Fmoc-peptides, as well as their self-assembly process. Additionally, we study the role of interactions between aromatic moieties in the self-assembly process and on the physical and structural properties of the hydrogels.     

Applications of Gelatin Methacryloyl (GelMA) Hydrogels in Microfluidic Technique-Assisted Tissue Engineering

In recent years, the microfluidic technique has been widely used in the field of tissue engineering. Possessing the advantages of large-scale integration and flexible manipulation, microfluidic devices may serve as the production line of building blocks and the microenvironment simulator in tissue engineering. Additionally, in microfluidic technique-assisted tissue engineering, various biomaterials are desired to fabricate the tissue mimicking or repairing structures (i.e., particles, fibers, and scaffolds). Among the materials, gelatin methacrylate (GelMA)-based hydrogels have shown great potential due to their biocompatibility and mechanical tenability. In this work, applications of GelMA hydrogels in microfluidic technique-assisted tissue engineering are reviewed mainly from two viewpoints: Serving as raw materials for microfluidic fabrication of building blocks in tissue engineering and the simulation units in microfluidic chip-based microenvironment-mimicking devices. In addition, challenges and outlooks of the exploration of GelMA hydrogels in tissue engineering applications are proposed.