Sonochemical Degradation of Gelatin Methacryloyl to Control Viscoelasticity for Inkjet Bioprinting

Inkjet printing enables the mimicry of the microenvironment of natural complex tissues by patterning cells and hydrogels at a high resolution. However, the polymer content of an inkjet-printable bioink is limited as it leads to strong viscoelasticity in the inkjet nozzle. Here it is demonstrated that sonochemical treatment controls the viscoelasticity of a gelatin methacryloyl (GelMA) based bioink by shortening the length of polymer chains without causing chemical destruction of the methacryloyl groups. The rheological properties of treated GelMA inks are evaluated by a piezo-axial vibrator over a wide range of frequencies between 10 and 10 000 Hz. This approach enables to effectively increase the maximum printable polymer concentration from 3% to 10%. Then it is studied how the sonochemical treatment effectively controls the microstructure and mechanical properties of GelMA hydrogel constructs after crosslinking while maintaining its fluid properties within the printable range. The control of mechanical properties of GelMA hydrogels can lead fibroblasts more spreading on the hydrogels. A 3D cell-laden multilayered hydrogel constructs containing layers with different physical properties is fabrictated by using high-resolution inkjet printing. The sonochemical treatment delivers a new path to inkjet bioprinting to build microarchitectures with various physical properties by expanding the range of applicable bioinks.     

Modular,synthetic, thiol-ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration

Natural polymers such as collagen are popular materials for tissue engineering scaffolds due to their innate bioactivity and biocompatibility. Being derived from animal sources, however, means that batch-to-batch consistency is often low and the extraction of collagen is costly. This conundrum facilitates the need for synthetic alternatives as scaffolding materials. In this study, a system of poly(ethylene glycol) (PEG)-based thiol-ene coupled (TEC) hydrogel scaffolds is presented for tissue engineering purposes. The platform includes several necessary features, namely cytocompatibility, high swelling ability, biodegradability, tunable stiffness, and fast, straightforward fabrication. The swelling ability is provided by the hydrophilicity of the ether-links of PEG, which facilitated the formation of high water content hydrogels that match the water content of soft tissues for the proper diffusion of nutrients and waste compounds. TEC ensures fast and facile fabrication, with cross-linking moieties that allow for the biodegradation of the hydrogel network through hydrolytic cleavage. The mechanical properties of the scaffolds are made tunable in the range of storage moduli spanning <1 kPa to >100 kPa. It is also shown that despite the synthetic nature of the hydrogels, human dermal fibroblasts and murine macrophages, Raw 264.7, were able to survive and produce extracellular protein excretions while embedded in the 3D hydrogels.     

A flexible rapid self-assembly scaffold-net DNA hydrogel exhibiting cell mobility control

DNA hydrogels have unique properties, such as specific identifiable molecular structures, programmable self-assembly, and excellent biocompatibility, which have led to increasing researches in the field of nanomaterials and biomedical over the past two decades. However, effective methods to regulate the microstructure of DNA hydrogels still lack, which limits their applications in tissue engineering. By introducing DNA scaffolds into rolling circle amplification (RCA) products and implementing rapid self-assembly strategy, we can produce a regulable new type scaffold-net DNA hydrogel in a short time. Scaffolds concentration and RCA time can regulate the microcharacteristics and physical properties of hydrogels. Scaffold-net DNA hydrogels will be a promising bionic platform for the studies of cancer cell metastatic and microenvironment biophysics.     

Rapid Formation of a Supramolecular Polypeptide–DNA Hydrogel for In Situ Three‐Dimensional Multilayer Bioprinting

A rapidly formed supramolecular polypeptide–DNA hydrogel was prepared and used for in situ multilayer three‐dimensional bioprinting for the first time. By alternative deposition of two complementary bio‐inks, designed structures can be printed. Based on their healing properties and high mechanical strengths, the printed structures are geometrically uniform without boundaries and can keep their shapes up to the millimeter scale without collapse. 3D cell printing was demonstrated to fabricate live‐cell‐containing structures with normal cellular functions. Together with the unique properties of biocompatibility, permeability, and biodegradability, the hydrogel becomes an ideal biomaterial for 3D bioprinting to produce designable 3D constructs for applications in tissue engineering.     

Light-Based 3D Printing of Gelatin-Based Biomaterial Inks to Create a Physiologically Relevant In Vitro Fish Intestinal Model

To provide prominent accessibility of fishmeal to the European population, the currently available, time- and cost-extensive feeding trials, which evaluate fish feed, should be replaced. The current paper reports on the development of a novel 3D culture platform, mimicking the microenvironment of the intestinal mucosa in vitro. The key requirements of the model include sufficient permeability for nutrients and medium-size marker molecules (equilibrium within 24 h), suitable mechanical properties (G' < 10 kPa), and close morphological similarity to the intestinal architecture. To enable processability with light-based 3D printing, a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink is developed and combined with Tween 20 as porogen to ensure sufficient permeability. To assess the permeability properties of the hydrogels, a static diffusion setup is utilized, indicating that the hydrogel constructs are permeable for a medium size marker molecule (FITC-dextran 4 kg mol⁻¹). Moreover, the mechanical evaluation through rheology evidence a physiologically relevant scaffold stiffness (G' = 4.83 ± 0.78 kPa). Digital light processing-based 3D printing of porogen-containing hydrogels results in the creation of constructs exhibiting a physiologically relevant microarchitecture as evidenced through cryo-scanning electron microscopy. Finally, the combination of the scaffolds with a novel rainbow trout (Oncorhynchus mykiss) intestinal epithelial cell line (RTdi-MI) evidence scaffold biocompatibility.     

甲基丙烯酰胺基明胶水凝胶研究进展

甲基丙烯酰胺基明胶(GelMA)水凝胶的制备及其在生物医学领域的应用是最近十几年的研究热点。GelMA水凝胶因其独特的光致交联特性,可以加工成不同形貌的水凝胶支架材料,同时,因其具有可控的力学性能、降解性能,以及优秀的生物相容性,已成为具有广泛应用前景的生物高分子聚合物材料。本文主要介绍了GelMA水凝胶在止血材料、创伤敷料、组织工程支架、药物控释、骨缺损修复等领域的研究进展。     

层状纳米纤维素膜/PVA复合水凝胶的制备与力学性能研究

采用叠层复合与物理相分离的方法制备了层状纳米细菌纤维素(BC)膜/聚乙烯醇( PVA)复合水凝胶.研究了聚乙烯醇的质量百分数、BC膜的复合层数以及制备条件对复合水凝胶力学性能的影响;通过扫描电镜( SEM)观察比较了复合水凝胶中BC膜层与PVA界面结合情况.结果表明,复合水凝胶的力学性能与PVA的质量百分数和BC膜含水...     

pH敏感型聚谷氨酸/透明质酸基互穿网络医用水凝胶的制备及表征

生物材料是推动生物医学领域日新月异变化的基石,医用水凝胶作为重要成员,近年来表现出蓬勃发展的态势。文章介绍了一种新型可注射的、以生物相容性方法交联的聚谷氨酸(Poly (γ-glutamic acid), PGA)/透明质酸(Hyaluronic acid, HA)复合水凝胶。研究首先采用EDC/NHS方法合成了酪胺(Tyramine,Ty)接枝聚谷氨酸的PGA-Ty前体大分子及半胱胺(Cysteamine, CA)修饰透明质酸的HA-CA前体大分子。两种前体大分子的结构分别使用核磁和红外进行了确证。得到的两种前体大分子在低浓度双氧水和辣根过氧化物酶(Horseradish Peroxidase, HRP)的共同作用下,于水相中交联得到互穿网络(Interpenetrating Network, IPN)水凝胶。实验对IPN水凝胶样品的系列性能,如平衡含水量、内部形貌、酶降解速率以及力学性能等进行了测试,并选取了盐酸四环素为药物模型对凝胶的体外药物释放行为、体外抗菌效果进行了测评。凝胶材料的细胞毒性及凝胶支架对细胞3D培养的效果证明其生物相容性优异,体外包埋的细胞经72h培养,未表现出明显细胞毒性。系列数据证明,该种水凝胶可以设计成为pH敏感型的药物控释载体材料,并因其良好的生物相容性,也有作为细胞支架、创伤辅料等其它生物医用材料的潜力。     

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。     

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.     

Cell-Encapsulating Hydrogel Puzzle: Polyrotaxane-Based Self-Healing Hydrogels

Slide-ring hydrogels using polyrotaxanes have been developed as highly tough soft materials. However, they have never been used as biomaterials because of the lack of biocompatibility. Meanwhile, self-healing hydrogels are expected to improve fatigue resistance and extend the period of use. However, owing to the lack of high mechanical strength, they are limited in their use as biomaterials. Here we first developed a biocompatible self-healing/slide-ring hydrogel using glycol chitosan and a water-soluble polyrotaxane. We obtained excellent mechanical toughness and biocompatibility to promote the proliferation of human umbilical vein endothelial cells (HUVECs) encapsulated in the hydrogel. Owing to the rapid self-healing property, the cell-encapsulating gels adjusted arbitrarily, maintaining good cell proliferation function. Therefore, slide-ring hydrogels enable the use of biomaterials for soft-tissue engineering.     

Hofmeister效应辅助的蛋白质基水凝胶应变传感器

以酪蛋白酸钠和明胶为原料, 通过简单的在硫酸铵溶液中浸泡的方法, 借助Hofmeister效应制备了一种强韧导电的酪蛋白酸钠/明胶水凝胶, 克服了蛋白质基水凝胶柔软、 易碎的问题. 测试结果表明, 该水凝胶具有优异的机械性能, 最大拉伸应力为3.55 MPa, 最大拉伸应变为1375%; 水凝胶的最大电导率为0.0954 S/cm, 导电灵敏因子为0.53. 用该水凝胶制备的传感器对不同大小及不同速率的应变均具有分辨能力, 能够监测人体不同部位的运动, 且传感器的信号传输具有稳定性和准确性, 表明该水凝胶是监测人体健康和运动的理想材料. 该水凝胶还具有良好的形状记忆性能. 这一策略为制备全天然蛋白质基水凝胶开辟了新的思路, 扩展了水凝胶在生物医学和电子传感等相关领域的应用前景.     

Modified silicon carbide NPs reinforced nanocomposite hydrogels based on alginate-gelatin by with high mechanical properties for tissue engineering

Hydrogels are encouraging for different clinical purposes because of their high water absorption and mechanical relation to native tissues. Injectable hydrogels can modify the invasiveness of utilization, which decreases recovery and surgical costs. Principal designs applied to create injectable hydrogels incorporate in situ formation owing to chemical or/and physical crosslinking. Here, we report nontoxic, thermosensitive, injectable hydrogels composed of gelatin (GEL) and oxidized alginate (OA) reinforced by silicon carbide nanoparticles (SiC NPs) and crosslinked with N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The mechanical characteristics of the hydrogels were examined via rheological analysis. The outcomes reveal that extending the SiC NPs contents enhances the mechanical properties around five times. The cross-sectional microstructure of the scaffolds comprising 0.25, 1.0, and 1.5% SiC NPs was scrutinized by FESEM, verifying porous structure with interconnected pores. Because of the smaller pore sizes in the hydrogels, the swelling rate has reduced at the higher content of SiC, which diminishes the water uptake. Additionally, the biodegradation study unveils that the hydrogels with SiC are more long-lasting than the hydrogel without SiC. By adding SiC NPs, a decrease is observed in the biodegradation and swelling ratio. The scaffold with a higher SiC NPs content (1.5%) manifested better cell attachment and was less cytotoxic than hydrogel without SiC. OA/GEL composites embedded SiC NPs have manifested excellent physical properties for tissue engineering in comparison with hydrogel without nanoparticles.     

A soft lithography method to generate arrays of microstructures onto hydrogel surfaces

Materials bearing microscale patterns on the surface have important biomedical applications such as scaffolds in tissue engineering, drug delivery systems, sensors, and actuators. Hydrogels are an attractive class of materials that has excellent biocompatibility, biodegradability, and tunable mechanical properties that meet the requirements of the aforementioned applications. Generating patterns of intricate microstructures onto the hydrogel surfaces, however, is challenging due to properties such as the crosslinking density, low mechanical strength, adhesion, or chemical incompatibility of hydrogels with various molds. Here, we report the use of a soft lithography technique to successfully transfer arrays of micropillars onto a poly(2‐hydroxyethyl methacrylate)‐based hydrogel. The swelling of the hydrogel in solvents, such as phosphate‐buffered saline, deionized water, 60% ethanol, and absolute ethanol, facilitates the reproducible replication of the pattern. Furthermore, the micropillar pattern promotes the attachment of HeLa cells onto this hydrogel which is not inherently adhesive when unpatterned. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1144–1157     

氧化石墨烯/聚合物复合水凝胶的研究进展

氧化石墨烯是一种具有单原子厚度的二维材料, 具有优异的力学性能和良好的水分散性, 其表面有大量的含氧官能团. 将氧化石墨烯引入水凝胶体系中可以提高水凝胶的机械性能, 丰富其刺激响应的类型. 目前, 氧化石墨烯水凝胶在高强度、 吸附、 自愈合及智能材料等很多领域均有出色的表现. 氧化石墨烯水凝胶的研究已有10年的历史. 本文总结了氧化石墨烯水凝胶的制备方法, 归纳了智能氧化石墨烯水凝胶在光热响应、 pH响应和自愈合3个方面的响应机理和研究进展, 并综合评述了其在高强度水凝胶、 生物医学、 智能材料和污水处理等方面的应用前景.     

Tunable biohybrid hydrogels from coacervation of hyaluronic acid and PEO-based block copolymers

Accurately tuning the macroscopic properties of biopolymer-based hydrogels remains challenging due to the ill-defined molecular architecture of the natural building blocks. Here, we report a biohybrid coacervate hydrogel, combining the biocompatibility and biodegradability of naturally occurring hyaluronic acid (HA) with the tunability of a synthetic polyethylene oxide (PEO) -based ABA-triblock copolymer. Coacervation of the cationic ammonium or guanidinium-functionalized copolymer A-blocks with the anionic HA leads to hydrogel formation. Both mechanical properties and water content of the self-healing hydrogels can be controlled independently by altering the copolymer structure. By controlling the strength of the interaction between the polymer network and small-molecule cargo, both release rate and maximum release are controlled. Finally, we show that coacervation of HA and the triblock copolymer leads to increased biostability upon exposure to hyaluronidase. We envision that noncovalent crosslinking of HA hydrogels through coacervation is an attractive strategy for the facile synthesis of tunable hydrogels for biomedical applications.     

Effects of Processing Parameters of 3D Bioprinting on the Cellular Activity of Bioinks

In this review, few established cell printing techniques along with their parameters that affect the cell viability during bioprinting are considered. 3D bioprinting is developed on the principle of additive manufacturing using biomaterial inks and bioinks. Different bioprinting methods impose few challenges on cell printing such as shear stress, mechanical impact, heat, laser radiation, etc., which eventually lead to cell death. These factors also cause alteration of cells phenotype, recoverable or irrecoverable damages to the cells. Such challenges are not addressed in detail in the literature and scientific reports. Hence, this review presents a detailed discussion of several cellular bioprinting methods and their process‐related impacts on cell viability, followed by probable mitigation techniques. Most of the printable bioinks encompass cells within hydrogel as scaffold material to avoid the direct exposure of the harsh printing environment on cells. However, the advantages of printing with scaffold‐free cellular aggregates over cell‐laden hydrogels have emerged very recently. Henceforth, optimal and favorable crosslinking mechanisms providing structural rigidity to the cell‐laden printed constructs with ideal cell differentiation and proliferation, are discussed for improved understanding of cell printing methods for the future of organ printing and transplantation.     

Tough polyion complex hydrogel films of natural polysaccharides

The developments of tough hydrogels in recent years have greatly expanded the applications of hydrogels as structural materials. However, most of the tough hydrogels are made of synthetic polymers. To develop biopolymer-based tough hydrogels has both fundamental and practical significances. Here we report a series of polysaccharides-based tough hydrogel films prepared by polyion complexation and solvent evaporation of chondroitin sulfate(CS) and protonated chitosan(CHT) solutions with different weight ratios. The obtained CS/CHT gel films with thickness of 40-80 μm and water content of 66 wt%-81 wt% possess excellent mechanical properties, with tensile breaking stress and breaking strain being 0.4-3 MPa and 160%-320%, respectively. We found that in the mixture solutions there are large amounts of excess CHT in terms of charges; after swelling the films in water, the acetic acid, which is used to protonate the amino groups of CHT, diffuses out of the gel matrix, enhancing the intermolecular interactions between CHT molecules and thus improving the mechanical properties of gel films, besides the ionic bonds between CS and CHT. Antimicrobial tests also showed that the gel films with low weight ratio of CS to CHT, corresponding to the case with excess CHT, have evident antimicrobial effect. These CS/CHT gel films with good mechanical properties and antimicrobial effect should extend the applications of hydrogels in biomedical fields.     

Understanding mechanical characteristics of cellulose nanocrystals reinforced PHEMA nanocomposite hydrogel: in aqueous cyclic test

Cellulose nanocrystals (CNC) can be embedded within hydrogels to form tough and strong nanocomposite materials, which possess biomimetic properties from hydrogels including good biocompatibility, permeability and flexible mechanical characteristics. There are many potential applications for these strong nanocomposite hydrogels in medical devices, such as wound dressing or super absorbents. Whereas, the research on the mechanical properties of CNC reinforced nanocomposite remains at superficial level, and their nonlinear mechanical responses are rarely investigated in previous reports. Mechanical characteristics of CNC reinforced poly(2-hydroxyethyl methacrylate) (PHEMA) nanocomposite hydrogels, in terms of stress–strain correlations, fracture mechanism, and cyclic stretching responses, have been investigated in this work. Experimental results show that the modulus of the nanocomposite hydrogel tends to increase with increasing CNC content. Theoretical foundation for analysing the mechanical properties of hydrogels based on Mooney–Rivlin hyperelastic model, Voigt model and Reuss model has been developed and validated, which provides the prediction of the mechanical responses of CNC reinforced nanocomposite hydrogel to tension, especially the nonlinear responding behaviour.     

Comparison of nano- and microfibrillated cellulose films

Nanocellulose is an interesting building block for functional materials and has gained considerable interest due to its mechanical robustness, large surface area and biodegradability. It can be formed into various structures such as solids, films and gels such as hydrogels and aerogels and combined with polymers or other materials to form composites. Mechanical, optical and barrier properties of nanofibrillated cellulose (NFC) and microfibrillated cellulose (MFC) films were studied in order to understand their potential for packaging and functional printing applications. Impact of raw material choice and nanocellulose production process on these properties was evaluated. MFC and NFC were produced following two different routes. NFC was produced using a chemical pretreatment followed by a high pressure homogenization, whereas MFC was produced using a mechanical treatment only. TEMPO-mediated oxidation followed by one step of high pressure (2,000 bar) homogenization seems to produce a similar type of NFC from both hardwood and softwood. NFC films showed superior mechanical and optical properties compared with MFC films; however, MFC films demonstrated better barrier properties against oxygen and water vapor. Both the MFC and NFC films were excellent barriers against mineral oil used in ordinary printing inks and dichlorobenzene, a common solvent used in functional printing inks. Barrier properties against vegetable oil were also found to be exceptionally good for both the NFC and MFC films.