基于动态化学的自愈性水凝胶及其在生物医用材料中的应用研究展望

自愈性材料具有自我修复损伤的特点, 能够增加使用材料的安全性, 延长材料寿命, 是一种具有损伤管理性能的智能新材料. 基于动态化学的自愈性水凝胶是近来备受关注的一种自愈性材料, 由具有动态特性的交联网络构建形成. 交联作用为动态化学键, 即非共价键, 如弱相互作用的氢键、分子间作用力(范德华力)、配位作用、亲疏水作用等, 或可逆共价键, 如温和条件下可逆的亚胺键、双硫键、酰腙键等. 这种材料具有本征性的自愈性, 一方面可应对外界破坏造成的损伤, 进行自我修复. 另一方面动态化学键对多种环境刺激具有响应性, 能自我调节以适应环境变化, 为将自愈性水凝胶开发为自适性多功能智能新材料奠定了基础. 水凝胶具有优越的生物相容性以及和生物组织的相似性, 在生物医用材料中如药物控制释放、组织工程修复、生物仿生等领域发挥着越来越大的作用, 而开发具有自愈性的多功能智能水凝胶, 将进一步拓展其应用. 综述了近来基于动态化学的自愈性水凝胶的制备及其在生物医用材料领域中的应用研究.     

基于动态建构化学的自愈合水凝胶及其在生物医学领域的应用展望

自愈合水凝胶与传统水凝胶相比,经受力破坏后仍可恢复其结构和功能,具有自我修复损伤的特点,是近年来备受关注的一种智能软材料.动态建构化学概念的引入,极大地促进了多响应性动态自愈合水凝胶的发展.本文综述了近年来基于动态建构化学合成自愈合水凝胶的方法,包括多重氢键作用、疏水相互作用、亚胺键、酰腙键等,并分析探讨了影响凝胶自愈合性能的因素及其在生物医学领域的潜在应用,还对其未来的发展进行了展望.     

一种新型光致发光自愈合水凝胶的合成

采用自由基聚合法制备了具有光致发光特性的自愈合水凝胶, 解决了光致发光配合物在水相荧光猝灭的问题. 通过分子设计, 利用共价键将油溶性的含Eu稀土配合物引进水凝胶体系中, 发现该配合物在水凝胶体系中稳定存在, 不扩散. 含Eu稀土配合物具有紫外光致发光的特性, 赋予该水凝胶良好的可识别性. 同时该水凝胶含有动态硼酸酯键, 其快速愈合的特性使该水凝胶在受损后能短时间内修复损伤, 为制备可发光水凝胶和可识别生物医用材料提供了新的思路.     

自愈性聚合物水凝胶的最新研究进展

主要阐述自愈性聚合物水凝胶的最新研究进展,针对自愈性聚合物水凝胶的愈合机理、不同类型聚合物对水凝胶的自愈性贡献、水凝胶的愈合程度及其验证方法等方面进行了分析和对比。总体而言,无论是在自愈性聚合物的分子设计,还是在其水凝胶的愈合机理研究方面,都取得了重要进展。然而,聚合物水凝胶的自愈合能力还有待进一步提高。新型聚合物设计、水凝胶制备方法的改进和自愈合效率的提高都会对自愈性聚合物水凝胶的进一步应用产生重要影响。     

自愈合凝胶:结构、性能及展望

作为一种高分子智能材料,自愈合凝胶在解决软材料损伤修复以及凝胶-生物体组织之间的界面接口问题,实现软材料智能化、高效化和环境友好化具有重要意义.近年来利用动态建构化学的基本原理,通过动态非共价键、可逆动态共价键相互作用,设计了一系列具有良好自愈合性能的新型凝胶材料.本文以物理型和化学型动态自愈合凝胶为例,综述了自愈合凝胶的分子设计思路、性能,并分析了影响自愈合性能因素,并对其未来的发展进行了展望.     

超分子形状记忆水凝胶研究进展

超分子形状记忆水凝胶(SSMHs)是一类利用超分子作用或动态共价键作为分子开关来固定临时形状,并能在特定的刺激下恢复初始形状的高分子水凝胶.本文简要介绍了SSMHs的定义和发展历程,总结了利用不同种类的可逆作用构建SSMHs的最新进展,并扩展介绍了具有多重形状记忆效应和多功能的SSMHs.最后,也对SSMHs所面临的挑战和未来发展方向进行了讨论.     

强韧型自愈合水凝胶的研究进展

水凝胶作为一种由大量水和与众不同的三维网状结构构成的智能软材料,已经广泛应用于许多领域,如药物输送、软骨修复、废物处理及电子设备等。然而,水凝胶不良的机械性能及自愈合性极大地限制了它们的潜在应用。目前已报道的韧性水凝胶通常不具有或只有很弱的自修复性,而自修复水凝胶通常机械性能非常弱。因此,研发具有高效自修复性能和优异机械性能的水凝胶材料,无论是从学术角度还是工业角度都是非常重要的。本文总结了近些年来强韧型自愈合水凝胶的最新研究进展,从其制备方法、性能等方面进行了简要介绍,并对未来的发展前景进行了展望。     

DNA水凝胶的制备及生物应用

DNA具有良好的生物相容性、生物可降解性、分子识别特性、纳米尺寸可控及特异编码等特性。近年来,DNA扮演了多种角色,不仅仅是作为生物体系的遗传物质,同样作为生物材料被用于纳米结构的构建。DNA水凝胶既保持了DNA本来的生物特性又兼具普通凝胶的特性,比如形状可塑性、一定的机械强度、输送物质等特性。DNA水凝胶按照凝胶形成化学键的类型可以分为共价键形成的化学凝胶和非共价键形成的物理凝胶; DNA水凝胶中可以引入特异性响应不同刺激的基团或者序列,从而实现对不同刺激的灵敏性响应进而拓宽DNA水凝胶的应用范围。按照刺激响应性分类可分为pH敏感型、光敏感型、温度敏感型和小分子敏感型等水凝胶。DNA水凝胶的这些特有的性质很好地将DNA纳米技术和生物技术连接起来,为其应用提供了广阔的前景。DNA水凝胶作为一种具有智能响应的材料也越来越多地被应用到生物传感、药物输送、三维细胞培养等方面。本文主要综述了DNA 水凝胶的分类以及近几年来DNA水凝胶中的不同刺激响应型DNA水凝胶的制备及其生物应用,最后对其以后的研究前景进行了展望。     

海藻酸动态共价交联水凝胶的制备及其自愈合性能

利用高碘酸钠氧化海藻酸得到带有醛基的海藻酸,利用水合肼与聚乙二醇反应得到末端为酰肼基的聚乙二醇,以二者为原料利用醛基与酰肼基反应形成酰腙键的动态化学反应,赋予天然生物大分子水凝胶优良的自愈性和p H响应性.通过红外光谱、核磁共振光谱、动态黏弹谱、电子万能试验机等表征了材料的结构、水凝胶的自愈合能力以及p H响应性.结果表明,该水凝胶具有良好的力学性能和自愈合能力,能够在不加热和不添加催化剂的情况下,在温和的生理环境下自发实现切口愈合.同时水凝胶具有p H响应性,在碱性环境中成凝胶,在酸性环境中则转变为溶液状态,并且这种凝胶—溶液转变可重复多次.这些优异的性能,加上简单的制备方法、良好的生物相容性将为这类材料在生物医用领域的应用提供坚实的基础.     

自愈合水凝胶的合成及在药物制剂中的应用进展

自愈水凝胶通过重新连接水凝胶基质内断裂的链路,实现裂纹闭合。自愈合水凝胶在物理损伤后恢复原来结构和功能,并且具有多重特性,如可注射性、导电性、粘合性,近年来越来越受到重视,并且广泛应用于制药工程、生物医学等领域。但是其韧性与快速愈合的相容性仍有待解决,在人体环境中的应用仍有待进一步研究。介绍了近年来具有快速自愈合能力和机械韧性水凝胶的创新型合成方法。以及其在医药学中的广泛应用。相信自愈合水凝胶在未来具有长远的发展前景及巨大的可能性。     

Self-healing Hydrogels and Underlying Reversible Intermolecular Interactions

Self-healing hydrogels have attracted growing attention over the past decade due to their biomimetic structure, biocompatibility, as well as enhanced lifespan and reliability, thereby have been widely used in various biomedical, electrical and environmental engineering applications. This feature article has reviewed our recent progress in self-healing hydrogels derived from mussel-inspired interactions, multiple hydrogen-bonding functional groups such as 2-ureido-4[1 H]-pyrimidinone(UPy), dynamic covalent bonds(e.g., Schiff base reactions and boronic ester bonds). The underlying molecular basics of these interactions, hydrogel preparation principles, and corresponding performances and applications are introduced. The underlying reversible intermolecular interaction mechanisms in these hydrogels were investigated using nanomechanical techniques such as surface forces apparatus(SFA) and atomic force microscopy(AFM), providing fundamental insights into the self-healing mechanisms of the hydrogels. The remaining challenging issues and perspectives in this rapidly developing research area are also discussed.     

Preparation and Characterization of Attractive Poly(amino acid)Hydrogels Based on 2-Ureido-4[1H]-pyrimidinone

Self-healing hydrogels with the shear-thinning property are novel injectable materials and are superior to traditional injectable hydrogels.The self-healing hydrogels based on 2-ureido-4[1 H]-pyrimidinone(UPy)have recently received extensive attention due to their dynamic reversibility of UPy dimerization.However,generally,UPy-based self-healing hydrogels exhibit poor stability,cannot degrade in vivo and can hardly be excreted from the body,which considerably limit their bio-application.Here,using poly(l-glutamic acid)(PLGA)as biodegradable matrix,branchingα-hydroxy-ω-amino poly(ethylene oxide)(HAPEO)as bridging molecule to introduce UPy,and ethyl acrylate polyethylene glycol(MAPEG)to introduce double bond,the hydrogel precursors(PMHU)are prepared.A library of the self-healing hydrogels has been achieved with well self-healable and shear-thinning properties.With the increase of MAPEG grafting ratio,the storage modulus of the self-healing hydrogels decreases.The self-healing hydrogels are stable in solution only for 6 h,hard to meet the requirements of tissue regeneration.Consequently,ultraviolet(UV)photo-crosslinking is involved to obtain the dual crosslinking hydrogels with enhanced mechanical properties and stability.When MAPEG grafting ratio is 35.5%,the dual crosslinking hydrogels can maintain the shape in phosphate-buffered saline solution(PBS)for at least 8 days.Loading with adipose-derived stem cell spheroids,the self-healing hydrogels are injected and self-heal to a whole,and then they are crosslinked in situ via UV-irradiation,obtaining the dual crosslinking hydrogels/cell spheroids complex with cell viability of 86.7%±6.0%,which demonstrates excellent injectability,subcutaneous gelatinization,and biocompatibility of hydrogels as cell carriers.The novel PMHU hydrogels crosslinked by quadruple hydrogen bonding and then dual photo-crosslinking of double bond are expected to be applied for minimal invasive surgery or therapies in tissue engineering.     

PREFACE

正We are delighted to present this special-themed issue of the Chinese Journal of Polymer Science(CJPS) devoted to the recent advances in self-healing polymeric materials. Selfhealing has been recognized as one of the most attractive topics for advanced polymers in the past few years, enabling their reworkability, durability and reliability.     

Bioinspired dual dynamic network hydrogels promote cartilage regeneration through regulating BMSC chondrogenic differentiation

How to improve the therapeutic efficacy of cell delivery during mechanical injection has been a great challenge for tissue engineering. Here, we present a facile strategy based on dynamic chemistry to prepare injectable hydrogels for efficient stem cell delivery using hyaluronic acid (HA) and poly(γ-glutamic acid) (γ-PGA). The combination of the guest–host (GH) complexation and dynamic hydrazone bonds enable the HA/γ-PGA hydrogels with physical and chemical dual dynamic network and endow hydrogels a stable structure, rapid self-healing ability, and injectability. The mechanical properties, self-healing ability, and adaptability can be programmed by changing the ratio of GH network to hydrazine bond cross-linked network. Benefitting from the dynamic cross-linking networks, mild preparation process, and cytocompatibility of HA/γ-PGA hydrogels, bone marrow mesenchymal stem cells (BMSCs) show high cell viability in this system following mechanical injection. Moreover, HA/γ-PGA hydrogels can promote BMSC proliferation and upregulate the expression of cartilage-critical genes. Notably, in a rabbit auricular cartilage defect model, BMSC-laden HA/γ-PGA hydrogels can effectively promote cartilage regeneration. Together, we propose a general strategy to develop injectable self-healing HA/γ-PGA hydrogels for effective stem cell delivery in cartilage tissue engineering.     

The Potential of Microencapsulated Self-healing Materials for Microcracks Recovery in Self-healing Composite Systems: A Review

The autonomic self-healing materials based on microcapsules have made major advancements for the repairing of microcracks in polymers and polymer composite systems. Self-healing encapsulated materials have the inborn ability to heal polymeric composites after being damaged by chemical and mechanical progressions. These intelligent micro-encapsulated self-healing materials possess great capabilities for recovering the mechanical as well aesthetic properties and barrier properties of the polymeric structures. Based on real world observations and experimental data, it is believed that microcracks and microcracking in polymeric materials can result because of many chemical and physical routes and is one of the foremost critical issues for polymeric materials. Especially in polymeric coatings, these microcracks can lead towards disastrous failure, and conventional healing systems like patching and welding cannot be used to repair microcracks at such a micro-level. Self-healing materials, especially, capsule based self-healing materials is a new field sought as an alternative to the conventional repairing techniques, requiring no manual intrusion and uncovering. This review covers the basic and major aspects of the microencapsulated self-healing approach like the effect of synthesis parameters on the size of microcapsules, healing efficiency determination, and the potential of the existing developed microencapsulated agents.     

Design and synthesis of self-healing polymers

Self-healing polymers represent a class of materials with built-in capability of rehabilitating damages. The topic has attracted increasingly more attention in the past few years. The on-going research activities clearly indicate that self-healing polymeric materials turn out to be a typical multi-disciplinary area concerning polymer chemistry, organic synthesis, polymer physics, theoretical and experimental mechanics, processing, composites manufacturing, interfacial engineering, etc. The present article briefly reviews the achievements of the groups worldwide, and particularly the work carried out in our own laboratory towards strength recovery for structural applications. To ensure sufficient coverage, thermoplastics and thermosetting polymers, extrinsic and intrinsic self-healing, autonomic and non-autonomic healing approaches are included. Innovative routes that correlate materials chemistry to full capacity restoration are discussed for further development from bioinspired toward biomimetic repair.     

(Bio)polymeric Hydrogels as Therapeutic Agents

Hydrogels derived from both natural and synthetic polymers have gained significant scientific attention in recent years for their potential use as biomedical materials to treat human diseases. While a great deal of research efforts have been directed towards investigating polymeric hydrogels as matrices for drug delivery systems, examples of such hydrogels exhibiting intrinsic therapeutic properties are relatively less common. Characteristics of synthetic and natural polymers such as high molecular weight, diverse molecular architecture, chemical compositions, and modulated molecular weight distribution are unique to polymers. These characteristics of polymers can be utilized to discover a new generation of drugs and medical devices. For example, polymeric hydrogels can be restricted to the gastrointestinal tract, where they can selectively recognize, bind, and remove the targeted disease-causing substances from the body without causing any systemic toxicity that are associated with traditional small molecule drugs. Similarly hydrogels can be implanted at specific locations (such as knee and abdomen) to impart localized therapeutic benefits. The present article provides an overview of certain recent developments in the design and synthesis of functional hydrogels that have led to several polymer derived drugs and biomedical devices. Some of these examples include FDA-approved marketed products.     

Highly stretchable,self-adhesive,and self-healable double network hydrogel based on alginate/polyacrylamide with tunable mechanical properties

A number of synthetic hydrogels suffer from low mechanical strength. Despite of the recent advances in the fabrication of tough hydrogels, it is still a great challenge to simultaneously construct high stretchability, and self-adhesive and self-healing capability in a hydrogel. Herein, a new type of double network hydrogel was prepared based on irreversible cross-linking of polyacrylamide chains and Schiff-base reversible cross-linking between glycidyl methacrylate-grafted ethylenediamine and oxidized sodium alginate (OSA). The combination of both cross-linkings and their synergistic effect provided a novel hydrogel with high strength, stretchable, rapid self-healing, and self-adhesiveness to different material. Besides, the hydrogels with diverse OSA content could maintain their original shapes after loading–unloading tensile test. The resulting hydrogel has a great potential in various fields for supporting and load-bearing substance.     

Macrocyclic supramolecular biomaterials in anti-cancer therapeutics

Macrocyclic supramolecular complexes demonstrate the dynamic potential to solve global biomedical challenges, a promising cancer treatment modality. The macrocyclic system is an important heterocyclic system widely present in natural products and synthetic molecules. The unique structural feature of macrocyclic supramolecular complexes with desirable donor & acceptor characteristics is beneficial for readily binding with various enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. Macrocyclic-related research and macrocyclic molecules-based medicinal chemistry developments have become rapidly developing areas of study. Numerous macrocyclic-based molecules as clinical drugs have been extensively used in the clinic to treat various diseases with high therapeutic potency. This critically analyzed work systematically reviews current developments of macrocyclic supramolecular complexes-based compounds in the range of medicinal chemistry as anticancer, anti-inflammatory, and other therapeutic agents, together with their potential applications in diagnostics and pathology. This review will be helpful for medicinal chemistry researchers to develop new thoughts in the quest for rational designs of more active and less toxic macrocyclic supramolecular complexes-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.