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。     

Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials

In recent years, intelligent hydrogels which can change their swelling behavior and other properties in response to environmental stimuli such as temperature, pH, solvent composition and electric fields, have attracted great interest. The hydrogels based on polysaccharides incorporated with thermo-responsive polymers have shown unique properties such as biocompatibility, biodegradability, and biological functions in addition to the stimuli-responsive characters. These "smart" hydrogels exhibit single or multiple stimuli-responsive characters which could be used in biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers. This review also screens the current applications of these hydrogels in the fields of drug delivery, tissue engineering and wound healing.     

水凝胶流变学研究概况

水凝胶具有良好的生物相容性和生物可降解性,其结构呈三维网状结构,与细胞外基质相似,在药物释放和组织工程等领域具有广阔的应用前景,被广泛地用于生物制药、生物材料和医学等领域。流变学可以描述材料的流动特性和力学性能,水凝胶的粘弹响应对材料内部结构的变化也非常敏感,因此流变行为被视为研究水凝胶的一种重要方法。本文综述了流变学方法在水凝胶研究中的应用,介绍了水凝胶流变学的研究方法,讨论了影响水凝胶流变学特征的因素,并展望了水凝胶流变学的发展前景。     

Natural or Natural-Synthetic Hybrid Polymer-Based Fluorescent Polymeric Materials for Bio-imaging-Related Applications

Fluorescent polymeric materials such as hydrogels and particles have been attracting attention in many biomedical applications including bio-imaging, optical sensing, tissue engineering, due to their good biocompatibility, biodegradability, and advanced optical property. This review article aims at summarizing recent progress in fluorescent hydrogels and particles based on natural polymers or natural-synthetic hybrid polymers as the building blocks with a concentration on their bio-imaging-related applications. The challenges and future perspectives for the development of natural or natural-synthetic hybrid polymer-based fluorescent hydrogels and particles are also presented.     

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。     

Characterization of Hydrogels Made of a Novel Spider Silk Protein eMaSp1s and Evaluation for 3D Printing

Recombinantly produced spider silk proteins have high potential for bioengineering and various biomedical applications because of their biocompatibility, biodegradability, and low immunogenicity. Here, the recently described small spider silk protein eMaSp1s is assembled into hydrogels, which can be 3D printed into scaffolds. Further, blending with a recombinantly produced MaSp2 derivative eADF4(C16) alters the mechanical properties of the resulting hydrogels. Different spider silk hydrogels also show a distinct recovery after a high shear stress deformation, exhibiting the tunability of their features for selected applications.     

Human Albumin-Based Hydrogels for Their Potential Xeno-Free Microneedle Applications

Nowadays, hydrogels-based microneedles (MNs) have attracted a great interest owing to their outstanding qualities for biomedical applications. For the fabrication of hydrogels-based microneedles as tissue engineering scaffolds and drug delivery carriers, various biomaterials have been tested. They are required to feature tunable physiochemical properties, biodegradability, biocompatibility, nonimmunogenicity, high drug loading capacity, and sustained drug release. Among biomaterials, human proteins are the most ideal biomaterials for fabrication of hydrogels-based MNs; however, they are mechanically weak and poorly processible. To the best of the knowledge, there are no reports of xeno-free human protein-based MNs so far. Here, human albumin-based hydrogels and microneedles for tissue engineering and drug delivery by using relatively new processible human serum albumin methacryloyl (HSAMA) are engineered. The resultant HSAMA hydrogels display tunable mechanical properties, biodegradability, and good biocompatibility. Moreover, the xeno-free HSAMA microneedles display a sustained drug release profile and significant mechanical strength to penetrate the model skin. In vitro, they also show good biocompatibility and anticancer efficacy. Sustainable processible human albumin-based biomaterials may be employed as a xeno-free platform in vivo for tissue engineering and drug delivery in clinical trials in the future.     

结冷胶与聚乙二醇丙烯酸酯双网络凝胶的制备及生物相容性评价

针对结冷胶脆性较大的问题,将聚乙二醇丙烯酸酯(PEGDA)引入结冷胶,通过紫外交联制备了结冷胶/PEGDA双网络凝胶,并对单组分凝胶和双网络凝胶的溶胀性能、微观形貌、拉伸力学性能、动态压缩性能和流变性能等进行比较.结果表明,双网络凝胶在类生理环境中具有较小的溶胀率和较好的尺寸稳定性,PEGDA的引入能够大幅度提高结冷胶的韧性,双网络凝胶的拉断伸长率可达340%,断裂能达1.01×103J/m2,与天然关节软骨相当.将成纤维细胞种植在凝胶内部进行体外三维立体培养,结果显示,细胞在凝胶内部生存状态良好,双网络凝胶的细胞负载率高于单网络结冷胶,说明该体系在生物医用领域具有良好的应用前景.     

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.     

水凝胶仿生柔性电子学

水凝胶力学性质与生物组织相似,生物相容性好,在生物电子学领域具有独特的优势.受生物组织——如皮肤、神经、肌肉等启发,发展了具有仿生结构和功能的水凝胶材料.以这种水凝胶材料制作而成的柔性电子器件具有感知温度、压力、应变、电场等外界刺激的功能,可模拟生物组织的传感能力,在仿生电子皮肤,人工肌肉,人工神经等领域具有重要的应用...     

Advanced Silk Fibroin Biomaterials-Based Microneedles for Healthcare

Microneedles are a promising transdermal drug delivery system that has the advantages of minimal invasiveness, painlessness, and on-demand drug delivery compared with commonly used medical techniques. Natural resources are developed as next-generation materials for microneedles with varying degrees of success. Among them, silk fibroin is a natural polymer obtained from silkworms with good biocompatibility, high hardness, and controllable biodegradability. These properties provide many opportunities for integrating silk fibroin with implantable microneedle systems. In this review, the research progress of silk fibroin microneedles in recent years is summarized, including their materials, processing technology, detection, drug release methods, and applications. Besides, the research and development of silk fibroin in a multidimensional way are analyzed. Finally, it is expected that silk fibroin microneedles will have excellent development prospects in various fields.     

The Application of Chitosan Nanostructures in Stomatology

Chitosan (CS) is a natural polymer with a positive charge, a deacetylated derivative of chitin. Chitosan nanostructures (nano-CS) have received increasing interest due to their potential applications and remarkable properties. They offer advantages in stomatology due to their excellent biocompatibility, their antibacterial properties, and their biodegradability. Nano-CSs can be applied as drug carriers for soft tissue diseases, bone tissue engineering and dental hard tissue remineralization; furthermore, they have been used in endodontics due to their antibacterial properties; and, finally, nano-CS can improve the adhesion and mechanical properties of dental-restorative materials due to their physical blend and chemical combinations. In this review, recent developments in the application of nano-CS for stomatology are summarized, with an emphasis on nano-CS’s performance characteristics in different application fields. Moreover, the challenges posed by and the future trends in its application are assessed.     

基于壳聚糖物理网络的高强韧双网络水凝胶的构建、调控与应用

双网络水凝胶由两个具有相反物理性质的交联网络构成,硬而脆的第一网络在变形过程中断裂耗散能量,从而增韧凝胶.当第一网络为具有重建能力的物理网络时,双网络水凝胶表现出优异的抗软化和机械稳定性.目前双网络水凝胶第一物理网络类型单一、结构和力学调控繁琐,因而其开发和应用受到限制.针对上述问题,作者发展了硬而脆的壳聚糖物理网络构...     

Rhodamine Mechanophore Functionalized Mechanochromic Double Network Hydrogels with High Sensitivity to Stress

Mechanochromic hydrogels, a new class of stimuli-responsive soft materials, have potential applications in a number of fields such as damage reporting and stress/strain sensing. We prepared a novel mechanochromic hydrogel using a strategy that has been developed to prepare dual-network(DN) hydrogels. A hydrophobic rhodamine derivative(Rh mechanophore) was covalently incorporated into a first network as a cross-linker. This first network embedded with Rh mechanophore within the DN hydrogel was pre-stretched. This guaranteed that the stress could be transferred extensively to the Rh-crosslinked first network once the hydrogel was under an applied force. Interestingly, we found that the threshold stress required to activate the mechanochromism of the hydrogel was less than 200 kPa, and much less than those in previous reports. Moreover, because of the excellent sensitivity of the hydrogel to stress, the DN hydrogel exhibited reversible freezing-induced mechanochromism. Benefiting from the sensitivity of Rh mechanophore to both p H and force, the DN hydrogel showed p H-regulated mechanochromic behavior. Our experimental results indicate that the preparation strategy we used introduces sensitive mechanochromism into the hydrogel and preserves the advantageous mechanical properties of the DN hydrogel. These results will be beneficial to the design and preparation of mechanochromic hydrogels with high stress sensitivity, and foster their practical applications in a number of fields such as damage reporting and stress/strain sensing.     

A Double Network Hydrogel with High Mechanical Strength and Shape Memory Properties

Double network (DN) hydrogels as one kind of tough gels have attracted extensive attention for their potential applications in biomedical and load-bearing fields. Herein, we import more functions like shape memory into the conventional tough DN hydrogel system. We synthesize the PEG-PDAC/P(AAm-co-AAc) DN hydrogels, of which the first network is a well-defined PEG (polyethylene glycol) network loaded with PDAC (poly(acryloyloxyethyltrimethyl ammonium chloride)) strands, while the second network is formed by copolymerizing AAm (acrylamide) with AAc (acrylic acid) and cross-linker MBAA (N, N'-methylenebisacrylamide). The PEG-PDAC/P(AAm-co-AAc) DN gels exhibits high mechanical strength. The fracture stress and toughness of the DN gels reach up to 0.9 MPa and 3.8 MJ/m³, respectively. Compared with the conventional double network hydrogels with neutral polymers as the soft and ductile second network, the PEG-PDAC/P(AAm-coAAc) DN hydrogels use P(AAm-co-AAc), a weak polyelectrolyte, as the second network. The AAc units serve as the coordination points with Fe³⁺ ions and physically crosslink the second network, which realizes the shape memory property activated by the reducing ability of ascorbic acid. Our results indicate that the high mechanical strength and shape memory properties, probably the two most important characters related to the potential application of the hydrogels, can be introduced simultaneously into the DN hydrogels if the functional monomer has been integrated into the network of DN hydrogels smartly.     

Advances in nitric oxide-releasing hydrogels for biomedical applications

Hydrogels provide a plethora of advantages to biomedical treatments due to their highly hydrophilic nature and tissue-like mechanical properties. Additionally, the numerous and widespread endogenous roles of nitric oxide have led to an eruption in research developing biomimetic solutions to the many challenges the biomedical world faces. Though many design factors and fabrication details must be considered, utilizing hydrogels as nitric oxide delivery vehicles provides promising materials in several applications. Such applications include cardiovascular therapy, vasodilation and angiogenesis, antimicrobial treatments, wound dressings, and stem cell research. Herein, a recent update on the progress of NO-releasing hydrogels is presented in depth. In addition, considerations for the design and fabrication of hydrogels and specific biomedical applications of nitric oxide-releasing hydrogels are discussed.     

生物合成聚羟基烷基酸酯的研究与开发进展

聚羟基烷基酸酯(PHA)是近20年来迅速发展起来的一种生物高分子材料,是一种具有高分子的基本性质的可热塑加工成型的聚酯.PHA最突出性能是具有优良的生物相容性和可生物降解性,因此在医学、药物、工业、农业等领域具有其独特的应用.本文综述了PHA的研究开发历史、国外发展概况、我国目前研究开发现状和国内外生物合成聚羟基烷基酸酯的研究与开发的一些最新研究成果,着重介绍了发掘具有高合成效率的新菌种、利用基因工程技术获取重组菌株、使用低成本碳源、开发合适的提取工艺等方面的工作.     

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), dynami...     

Physical, chemical, and chemical-physical double network of zwitterionic hydrogels

Zwitterionic hydrogels are very promising for biomedical applications. They are usually copolymerized with other polymers to improve their mechanical properties often at the expense of their biological properties. In this study, physically cross-linked poly(sulfobetaine methacrylate) (polySBMA) hydrogels were prepared, and their physical properties including phase behavior were investigated. Linear polySBMAs, with an average molecular weight ranging from 20.9 kDa to 316 kDa, were prepared via free radical polymerization at different KCl concentrations. The opaque-transparent phase transition of polySBMA-water mixtures were measured using a UV-vis spectrometer. Analysis from dynamic rheometry showed the formation of physically cross-linked hydrogels with mechanical ductility due to reversible charge interactions. Chemically cross-linked hydrogels were also prepared, and their swelling and mechanical properties were evaluated. It was found that the introduction of cross-linkers could lead to a decrease in the amount of physical cross-links in chemical hydrogels. In order to improve the mechanical properties of SBMA hydrogels, linear polySBMA was introduced to the network of chemically cross-linked polySBMA gels, creating a chemical-physical double network (DN) with both chemical and physical cross-links. The chemical-physical DN provides a desirable method to improve the mechanical properties of zwitterionic hydrogels without introducing other hydrophobic moieties.     

New semi-interpenetrating network hydrogels: synthesis, characterization and properties

Amphiphilic hydrogels composed of aliphatic polyesters and poly(ethylene glycol) have potential applications in drug delivery, tissue engineering and other biomedical devices due to their advantageous biological properties, biocompatibility and biodegradability. However, they also exhibit some shortcomings in terms of their reactivity, swelling and mechanical properties. To address these limitations, new semi-interpenetrating network (semi-IPN) hydrogels based on poly(ethylene glycol)-co-poly(epsilon-caprolactone) (PEG-PCL) diacrylate macromer and hydroxypropyl guar gum (HPGG) were prepared by a low intensity ultraviolet (UV) light irradiation method, and characterized by FT-IR, DSC and WAXD analysis. Their properties were evaluated by investigating the swelling kinetics, dynamic mechanical rheology and the release behavior for bovine serum albumin (BSA). It was found that the introduction of the semi-IPN structure and HPGG decreased the crystallinity of PEG segments in the hydrogel, and improved the swelling and mechanical properties of the hydrogel, as well as lowered the release percentage of BSA from the hydrogel. Such hydrogel materials may have more advantages as a potentially interesting platform for the design of medical devices.The elastic modulus (G') and viscous modulus (G') as a function of frequency for various hydrogel samples.