紫外光共聚交联制备GelMA/PEGDA水凝胶

为避免物理交联明胶基水凝胶的热不稳定性,以及化学方法交联明胶基水凝胶存在的毒性,本文采用丙烯酰化的方法将甲基丙烯酸酐(MA)与明胶反应,在明胶分子链上引入双键结构,并且实现了紫外光照射引发甲基丙烯酰胺基明胶(GelMA)与聚乙二醇双丙烯酸酯(PEGDA)共聚交联制备水凝胶。研究了不同的MA加入量对明胶修饰度的影响,并对GelMA/PEGDA交联水凝胶理化性质进行了测试和分析。结果表明:体系中PEGDA含量增加,能释放更多的自由基,增加交联反应的活性和程度,使水凝胶形成更加致密的三维网络结构。并且GelMA/PEGDA交联水凝胶在37℃比GelMA交联水凝胶更加稳定。GelMA/PEGDA交联水凝胶将来有望成为组织工程的支架材料。     

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。     

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。     

非共价键交联海藻酸钠水凝胶的制备与性能

天然多糖海藻酸钠制备的水凝胶具有优越的生物相容性和生物组织相似性,作为生物医用材料在药物控制释放、组织工程支架、抗菌材料及创伤敷料等领域发挥着越来越大的作用。本文在介绍海藻酸钠物化性质的基础上,重点综述了非共价键交联(静电作用、氢键、范德华力、亲疏水作用等)海藻酸钠水凝胶的制备方法以及性能表征方法,最后讨论了制备方法及性能表征研究中的一些需要解决的问题。     

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...     

生物黏合水凝胶研究进展

近年来,水凝胶在组织工程支架、伤口敷料和药物递送系统等生物医学领域得到广泛应用。其中,生物黏合水凝胶因具有良好的黏合强度和优异的生物相容性,并且可以替代传统的手术缝合用于止血及伤口处理而备受关注。本文在已有工作的基础上系统地概述了生物黏合水凝胶的制备方法,并详细地讨论了各种水凝胶的黏合机理。此外,总结了生物黏合水凝胶在生物医学中的应用,并展望了性能优异的生物黏合水凝胶的开发思路。     

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。     

pH敏感性智能水凝胶的设计及其应用

水凝胶是一种交联的三维网状亲水性聚合物材料,具有与生物组织相似的特点并且能够吸收大量的水分。作为智能水凝胶的一种,pH敏感性水凝胶因其结构中含有大量碱性或酸性基团从而具有一定的pH敏感性。凭借这些特性,近年来pH敏感性水凝胶在生物、医学、物理、环境、纺织等众多研究领域备受关注。本文围绕p H敏感性水凝胶的响应机制、分类以及应用三个方面进行综述。在响应机制上,本文从响应过程、影响因素和溶胀扩散模型三方面进行综述;在分类上,根据水凝胶敏感性的不同分为溶胀-收缩类和溶胶-凝胶类两类,并进一步根据pH作用范围的不同将溶胀-收缩类细分为阴离子类、阳离子类以及两性离子类,溶胀-收缩类细分为硼酸酯类、酰腙类以及亚胺类;在应用研究上,本文总结了其在医学、环境、生物、智能检测、功能材料等热门领域的研究情况。最后,对pH敏感性水凝胶的未来的发展方向进行了展望。     

生物可降解高分子交联剂的研究进展

交联剂是制备水凝胶不可或缺的成分,其组成和结构影响了水凝胶的性能及应用.生物可降解性和生物相容性是作为组织工程支架、药物载体等生物医用材料所必需具备的性能.利用生物可降解性物质作为交联剂来制备化学凝胶,赋予了水凝胶上述性能,满足其作为生物医用材料的要求,拓宽水凝胶应用领域.本文主要总结了近年来多糖类(壳聚糖类、海藻酸类...     

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。     

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.     

Precisely Controlled Delivery of Abaloparatide through Injectable Hydrogel to Promote Bone Regeneration

Side‐effects from allograft, limited bone stock, and site morbidity from autograft are the major challenges to traditional bone defect treatments. With the advance of tissue engineering, hydrogel injection therapy is introduced as an alternative treatment. Therapeutic drugs and growth factors can be carried by hydrogels and delivered to patients. Abaloparatide, as an analog of human recombinant parathyroid hormone protein (PTHrp) and an alternative to teriparatide, has been considered as a drug for treating postmenopausal osteoporosis since 2017. Since only limited cases of receiving abaloparatide with polymeric scaffolds have been reported, the effects of abaloparatide on pre‐osteoblast MC3T3‐E1 are investigated in this study. It is found that in vitro abaloparatide treatment can promote pre‐osteoblast MC3T3‐E1 cells’ viability, differentiation, and mineralization significantly. For the drug delivery system, 3D porous structure of the methacrylated gelatin (GelMA) hydrogel is found effective for prolonging the release of abaloparatide (more than 10 days). Therefore, injectable photo‐crosslinked GelMA hydrogel is used in this study to prolong the release of abaloparatide and to promote healing of defected bones in rats. Overall, data collected in this study show no contradiction and imply that Abaloparatide‐loaded GelMA hydrogel is effective in stimulating bone regeneration.     

Ionically Modified Gelatin Hydrogels Maintain Murine Myogenic Cell Viability and Fusion Capacity

For tissue engineering of skeletal muscles, there is a need for biomaterials which do not only allow cell attachment, proliferation, and differentiation, but also support the physiological conditions of the tissue. Next to the chemical nature and structure of the biomaterial, its response to the application of biophysical stimuli, such as mechanical deformation or application of electrical pulses, can impact in vitro tissue culture. In this study, gelatin methacryloyl (GelMA) is modified with hydrophilic 2-acryloxyethyltrimethylammonium chloride (AETA) and 3-sulfopropyl acrylate potassium (SPA) ionic comonomers to obtain a piezoionic hydrogel. Rheology, mass swelling, gel fraction, and mechanical characteristics are determined. The piezoionic properties of the SPA and AETA-modified GelMA are confirmed by a significant increase in ionic conductivity and an electrical response as a function of mechanical stress. Murine myoblasts display a viability of >95% after 1 week on the piezoionic hydrogels, confirming their biocompatibility. The GelMA modifications do not influence the fusion capacity of the seeded myoblasts or myotube width after myotube formation. These results describe a novel functionalization providing new possibilities to exploit piezo-effects in the tissue engineering field.     

Photo‐crosslinkable hydrogel‐based 3D microfluidic culture device

We developed the photo‐crosslinkable hydrogel‐based 3D microfluidic device to culture neural stem cells (NSCs) and tumors. The photo‐crosslinkable gelatin methacrylate (GelMA) polymer was used as a physical barrier in the microfluidic device and collagen type I gel was employed to culture NSCs in a 3D manner. We demonstrated that the pore size was inversely proportional to concentrations of GelMA hydrogels, showing the pore sizes of 5 and 25 w/v% GelMA hydrogels were 34 and 4 μm, respectively. It also revealed that the morphology of pores in 5 w/v% GelMA hydrogels was elliptical shape, whereas we observed circular‐shaped pores in 25 w/v% GelMA hydrogels. To culture NSCs and tumors in the 3D microfluidic device, we investigated the molecular diffusion properties across GelMA hydrogels, indicating that 25 w/v% GelMA hydrogels inhibited the molecular diffusion for 6 days in the 3D microfluidic device. In contrast, the chemicals were diffused in 5 w/v% GelMA hydrogels. Finally, we cultured NSCs and tumors in the hydrogel‐based 3D microfluidic device, showing that 53–75% NSCs differentiated into neurons, while tumors were cultured in the collagen gels. Therefore, this photo‐crosslinkable hydrogel‐based 3D microfluidic culture device could be a potentially powerful tool for regenerative tissue engineering applications.     

A 3D Bioprinted Nanoengineered Hydrogel with Photoactivated Drug Delivery for Tumor Apoptosis and Simultaneous Bone Regeneration via Macrophage Immunomodulation

One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects owing to the recruitment of local infection and delayed angiogenesis. Herein, a 3D printable multi-functional hydrogel composing polyphenolic carbon quantum dots (CQDs, 100 µg mL⁻¹) and gelatin methacryloyl (GelMA, 12 wt%) is reported for robust angiogenesis, bone regeneration and anti-tumor therapy. The CQDs are synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene. The 3D printed GelMA-CQDs hydrogels display typical shear-thinning behavior with excellent printability. The fabricated hydrogel displayed M2 polarization of macrophage (Raw 264.7) cells via enhancing anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs are able to produce vessel-like structures after 14 d of incubation. Furthermore, the 3D printed hydrogel scaffolds also show remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm⁻²) irradiation with controlled release of antitumor drugs (≈49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, it is anticipated that the tissue regeneration and healing ability with therapeutic potential of the GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation.     

Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells

Establishing the 3D microscale organization of cells has numerous practical applications, such as in determining cell fate (e.g., proliferation, migration, differentiation, and apoptosis) and in making functional tissue constructs. One approach to spatially pattern cells is by dielectrophoresis (DEP). DEP has characteristics that are important for cell manipulation, such as high accuracy, speed, scalability, and the ability to handle both adherent and non-adherent cells. However, widespread application of this method is largely restricted because there is a limited number of suitable hydrogels for cell encapsulation. To date, polyethylene glycol-diacrylate (PEG-DA) and agarose have been used extensively for dielectric patterning of cells. In this study, we propose gelatin methacrylate (GelMA) as a promising hydrogel for use in cell dielectropatterning because of its biocompatibility and low viscosity. Compared to PEG hydrogels, GelMA hydrogels showed superior performance when making cell patterns for myoblast (C2C12) and endothelial (HUVEC) cells as well as in maintaining cell viability and growth. We also developed a simple and robust protocol for co-culture of these cells. Combined application of the GelMA hydrogels and the DEP technique is suitable for creating highly complex microscale tissues with important applications in fundamental cell biology and regenerative medicine in a rapid, accurate, and scalable manner.     

Bottom-up approach to build osteon-like structure by cell-laden photocrosslinkable hydrogel

Based on photocrosslinkable PEGDMA and GelMA hydrogels, two "bottom-up" approaches ("circle-and-cross" and "layer-by-layer") were successfully developed to construct osteon-like structures with microchannel networks. Significantly, the "layer-by-layer" approach employing the GelMA hydrogel with a higher biocompatibility was more favorable for building biomimetic osteon.     

Hydrogel microfluidic co‐culture device for photothermal therapy and cancer migration

We developed the photo‐crosslinkable hydrogel microfluidic co‐culture device to study photothermal therapy and cancer cell migration. To culture MCF7 human breast carcinoma cells and metastatic U87MG human glioblastoma in the microfluidic device, we used 10 w/v% gelatin methacrylate (GelMA) hydrogels as a semi‐permeable physical barrier. We demonstrated the effect of gold nanorod on photothermal therapy of cancer cells in the microfluidic co‐culture device. Interestingly, we observed that metastatic U87MG human glioblastoma largely migrated toward vascular endothelial growth factor (VEGF)‐treated GelMA hydrogel‐embedding microchannels. The main advantage of this hydrogel microfluidic co‐culture device is to simultaneously analyze the physiological migration behaviors of two cancer cells with different physiochemical motilities and study gold nanorod‐mediated photothermal therapy effect. Therefore, this hydrogel microfluidic co‐culture device could be a potentially powerful tool for photothermal therapy and cancer cell migration applications.