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Bioactive Hydrogels Inspired by Laminin: An Emerging Biomaterial for Tissue Engineering Applications 受层粘蛋白启发的生物活性水凝胶:用于组织工程应用的新兴生物材料
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-22 DOI: 10.1002/mabi.202400207
Sweta Mohanty, Sangita Roy

Tissue or organ damage due to severe injuries or chronic diseases can adversely affect the quality of life. Current treatments rely on organ or tissue transplantation which has limitations including unavailability of donors, ethical issues, or immune rejection after transplantations. These limitations can be addressed by tissue regeneration which involves the development of bioactive scaffolds closely mimicking the extracellular matrix (ECM). One of the major components of ECM is the laminin protein which supports several tissues associated with important organs. In this direction, peptide-based hydrogels can effectively mimic the essential characteristics of laminin. While several reports have discussed the structure of laminin, the potential of laminin-derived peptide hydrogels as effective biomaterial for tissue engineering applications is yet to be discussed. In this context, the current review focuses on the structure of laminin and its role as an essential ECM protein. Further, the potential of short peptide hydrogels in mimicking the crucial properties of laminin is proposed. The review further highlights the significance of bioactive hydrogels inspired by laminin – in addressing numerous tissue engineering applications including angiogenesis, neural, skeletal muscle, liver, and adipose tissue regeneration along with a brief outlook on the future applications of these laminin-based hydrogels.

严重受伤或慢性疾病导致的组织或器官损伤会对生活质量产生不利影响。目前的治疗方法依赖于器官或组织移植,但这种方法有其局限性,包括无法获得供体、伦理问题或移植后的免疫排斥反应。组织再生可以解决这些局限性,它涉及到开发生物活性支架,使其紧密模拟细胞外基质(ECM)。细胞外基质的主要成分之一是层粘连蛋白,它支撑着与重要器官相关的多个组织。在这方面,肽基水凝胶能有效模拟层粘连蛋白的基本特性。虽然已有多篇报告讨论了层粘连蛋白的结构,但层粘连蛋白衍生肽水凝胶作为组织工程应用的有效生物材料的潜力仍有待讨论。在此背景下,本综述重点关注层粘连蛋白的结构及其作为一种重要 ECM 蛋白的作用。此外,还提出了短肽水凝胶在模仿层粘连蛋白关键特性方面的潜力。综述进一步强调了受层粘蛋白启发的生物活性水凝胶在解决众多组织工程应用(包括血管生成、神经、骨骼肌、肝脏和脂肪组织再生)方面的重要意义,并简要展望了这些基于层粘蛋白的水凝胶的未来应用。
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引用次数: 0
On the Development of Polylactic Acid/Polycaprolactone Blended Films with High Retention Capacity 开发具有高保留能力的聚乳酸/聚己内酯混合薄膜。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-18 DOI: 10.1002/mabi.202400272
Martina Cozzani, Pier Francesco Ferrari, Giacomo Damonte, Alessandro Pellis, Orietta Monticelli

The retention capacity of polymers is related to the development of systems that combine high surface-to-volume ratio with good handling and specific functionality. Biodegradability and biocompatibility are also key features for extending the field of applications to areas such as biomedicine. With this in mind, the aim of this work is to develop biodegradable, biocompatible, and highly functionalized porous films, that ensure suitable handling and a good surface-to-volume ratio. Polylactic acid (PLA) is applied as a polymer matrix to which a polycaprolactone with a star-shaped architecture (PCL-COOH) to ensure a high concentration of carboxylic end functionalities is added. The porous films are prepared using the phase inversion technique, which, as shown by Scanning Electron Microscopy (SEM) analysis, promotes good dispersion of the PCL-COOH domains. Absorption and release measurements performed with a positively charged model molecule show that the retention capacity and release rate can be tuned by changing the PCL-COOH concentration in the systems. Moreover, the adsorption properties for the formulation with the highest PCL-COOH content are also demonstrated with a real and widely used drug, namely doxorubicin. Finally, the bio- and hemocompatibility of the films, which are enzymatically degradable, are evaluated by using human keratinocytes and red blood cells, respectively.

聚合物的保留能力与开发兼具高表面体积比、良好操作性和特定功能性的系统有关。生物降解性和生物相容性也是将应用领域扩展到生物医学等领域的关键特征。有鉴于此,这项工作的目的是开发可生物降解、生物相容性和高度功能化的多孔薄膜,以确保合适的操作性和良好的表面体积比。聚乳酸(PLA)被用作聚合物基质,其中添加了具有星形结构的聚己内酯(PCL-COOH),以确保高浓度的羧基末端官能团。多孔薄膜采用相位反转技术制备而成,扫描电子显微镜(SEM)分析表明,该技术可促进 PCL-COOH 域的良好分散。利用带正电荷的模型分子进行的吸收和释放测量表明,可以通过改变系统中 PCL-COOH 的浓度来调整保留能力和释放率。此外,PCL-COOH 含量最高的制剂的吸附特性还通过实际广泛使用的药物(多柔比星)得到了证明。最后,还分别利用人体角质细胞和红细胞对可被酶降解的薄膜的生物相容性和血液相容性进行了评估。
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引用次数: 0
Masthead: Macromol. Biosci. 8/2024 刊头:Macromol.Biosci.8/2024
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-14 DOI: 10.1002/mabi.202470019
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引用次数: 0
Dual-Functional Implant Based on Gellan-Xanthan Hydrogel with Diopside, BMP-2 and Lysostaphin for Bone Defect Repair and Control of Staphylococcal Infection 基于含有地奥赛德、BMP-2 和溶血素的结冷黄原水凝胶的双功能植入体,用于骨缺损修复和葡萄球菌感染控制。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-14 DOI: 10.1002/mabi.202400205
Anna S. Karyagina, Alexander V. Grishin, Alina G. Kudinova, Inna N. Bulygina, Elizaveta V. Koudan, Polina A. Orlova, Vera P. Datsenko, Anna V. Zhulina, Tatyana M. Grunina, Maria S. Poponova, Mikhail S. Krivozubov, Maria S. Gromova, Natalia V. Strukova, Maria S. Generalova, Kirill E. Nikitin, Igor V. Shchetinin, Lev O. Luchnikov, Svetlana V. Zaitseva, Maria A. Kirsanova, Eugene S. Statnik, Fedor S. Senatov, Vladimir G. Lunin, Alexander V. Gromov

A new dual-functional implant based on gellan-xanthan hydrogel with calcium-magnesium silicate ceramic diopside and recombinant lysostaphin and bone morphogenetic protein 2 (BMP-2)-ray is developed. In this composite, BMP-2 is immobilized on microparticles of diopside while lysostaphin is mixed directly into the hydrogel, providing sustained release of BMP-2 to allow gradual bone formation and rapid release of lysostaphin to eliminate infection immediately after implantation. Introduction of diopside of up to 3% (w/v) has a negligible effect on the mechanical properties of the hydrogel but provides a high sorption capacity for BMP-2. The hydrogels show good biocompatibility and antibacterial activity. Lysostaphin released from the implants over a 3 h period efficiently kills planktonic cells and completely destroys 24 h pre-formed biofilms of Staphylococcus aureus. Furthermore, in vivo experiments in a mouse model of critically-sized cranial defects infected with S. aureus show a complete lack of osteogenesis when implants contain only BMP-2, whereas, in the presence of lysostaphin, complete closure of the defect with newly formed mineralized bone tissue is observed. Thus, the new implantable gellan-xanthan hydrogel with diopside and recombinant lysostaphin and BMP-2 shows both osteogenic and antibacterial properties and represents a promising material for the treatment and/or prevention of osteomyelitis after bone trauma.

本研究开发了一种新型双功能植入物,它基于结冷胶-黄原胶水凝胶与钙镁硅酸盐陶瓷透辉石以及重组溶血磷脂和骨形态发生蛋白 2(BMP-2)-射线。在这种复合材料中,BMP-2 被固定在透辉石微粒上,而溶血素则直接混入水凝胶中,从而实现了 BMP-2 的持续释放,使骨逐渐形成,而溶血素的快速释放则可在植入后立即消除感染。引入高达 3%(w/v)的透辉石对水凝胶的机械性能影响微乎其微,但却为 BMP-2 提供了很高的吸附能力。水凝胶具有良好的生物相容性和抗菌活性。植入物在 3 小时内释放的溶血萘能有效杀死浮游细胞,并在 24 小时内完全破坏金黄色葡萄球菌预先形成的生物膜。此外,在感染了金黄色葡萄球菌的重度颅骨缺损小鼠模型中进行的体内实验表明,当植入物仅含有 BMP-2 时,完全没有骨生成,而在溶血磷存在的情况下,可以观察到新形成的矿化骨组织使缺损完全闭合。因此,含有透辉石、重组溶血素和 BMP-2 的新型植入性结冷黄原胶水凝胶具有成骨和抗菌特性,是治疗和/或预防骨创伤后骨髓炎的理想材料。
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引用次数: 0
Nanoclay Hydrogel Microspheres with a Sandwich-Like Structure for Complex Tissue Infection Treatment 用于治疗复杂组织感染的具有三明治结构的纳米粘土水凝胶微球
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-14 DOI: 10.1002/mabi.202470018
Kunyuan Han, Jishizhan Chen, Qinglin Han, Lei Sun, Xieping Dong, Gengqiang Shi, Runhuai Yang, Wenqing Wei, Yunzhang Cheng

Front Cover: The human bone background visually demonstrates the effectiveness of hydrogel microspheres as a promising treatment for complex tissue infections caused by osteomyelitis. The injectable hydrogel microspheres, with their sandwich-like structure, allow controlled release of different types of metal ions that work together to eliminate bacteria. The lightning strike imagery vividly illustrates the antibacterial effect resulting from the interaction between microspheres and bacteria. More details can be found in article 2400027 by Yunzhang Cheng and co-workers.

封面:人体骨骼背景直观地展示了水凝胶微球作为治疗骨髓炎引起的复杂组织感染的有效方法。这种可注射的水凝胶微球具有类似三明治的结构,可控制释放不同类型的金属离子,共同消除细菌。雷击图像生动地展示了微球与细菌相互作用产生的抗菌效果。更多详情,请参阅程云章及其合作者的文章 2400027。
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引用次数: 0
Surface Immobilization of Oxidized Carboxymethyl Cellulose on Polyurethane for Sustained Drug Delivery 氧化羧甲基纤维素在聚氨酯上的表面固定化用于持续给药
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-12 DOI: 10.1002/mabi.202400229
Manali Somani, Chetna Verma, Flavius Phrangsngi Nonglang, Surya Bhan, Bhuvanesh Gupta

Polyurethane (PU) has a diverse array of customized physical, chemical, mechanical, and structural characteristics, rendering it a superb option for biomedical applications. The current study involves modifying the polyurethane surface by the process of aminolysis (aminolyzed polyurethane; PU-A), followed by covalently immobilizing Carboxymethyl cellulose (CMC) polymer utilizing Schiff base chemistry. Oxidation of CMC periodically leads to the creation of dialdehyde groups along the CMC chain. When the aldehyde groups on the OCMC contact the amine group on a modified PU surface, they form an imine bond. Scanning electron microscopy (SEM), contact angle, and X-ray photoelectron spectroscopy (XPS) techniques are employed to analyze and confirm the immobilization of OCMC on aminolyzed PU film (PU-O). The OCMC gel incorporates Nitrofurantoin (NF) and immobilizes it on the PU surface (PU-ON), creating an antibacterial PU surface. The confirmation of medication incorporation is achieved using EDX analysis. The varying doses of NF have demonstrated concentration-dependent bacteriostatic and bactericidal effects on both Gram-positive and Gram-negative bacteria, in addition to sustained release. The proposed polyurethane (PU-ON) surface exhibited excellent infection resistance in in vivo testing. The material exhibited biocompatibility and is well-suited for biomedical applications.

聚氨酯(PU)具有各种定制的物理、化学、机械和结构特性,是生物医学应用的绝佳选择。目前的研究包括通过氨基溶解(氨基溶解聚氨酯;PU-A)过程对聚氨酯表面进行改性,然后利用席夫碱化学共价固定羧甲基纤维素(CMC)聚合物。CMC 周期性氧化会在 CMC 链上产生醛基。当 OCMC 上的醛基接触到改性聚氨酯表面的胺基时,就会形成亚胺键。扫描电子显微镜(SEM)、接触角和 X 射线光电子能谱(XPS)技术被用来分析和确认 OCMC 在氨基化聚氨酯薄膜(PU-O)上的固定情况。OCMC 凝胶吸附了硝基呋喃妥因 (NF) 并将其固定在聚氨酯表面 (PU-ON),形成了抗菌聚氨酯表面。药物吸附的确认是通过 EDX 分析实现的。不同剂量的 NF 对革兰氏阳性菌和革兰氏阴性菌都具有浓度依赖性的抑菌和杀菌作用,而且还能持续释放。拟议的聚氨酯(PU-ON)表面在体内测试中表现出优异的抗感染能力。该材料具有生物相容性,非常适合生物医学应用。
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引用次数: 0
Star-Like Polypeptides as Simplified Analogues of Horseradish Peroxidase (HRP) Metalloenzymes 作为辣根过氧化物酶 (HRP) 金属酶简化类似物的星状多肽。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-09 DOI: 10.1002/mabi.202400155
Antoine Tronnet, Pedro Salas-Ambrosio, Rosa Roman, Lourdes Monica Bravo-Anaya, Marcela Ayala, Colin Bonduelle

Peroxidases, like horseradish peroxidase (HRP), are heme metalloenzymes that are powerful biocatalysts for various oxidation reactions. By using simple grafting-from approach, ring-opening polymerization (ROP), and manganese porphyrins, star-shaped polypeptides analogues of HRP capable of catalyzing oxidation reactions with H2O2 is successfully prepared. Like their protein model, these simplified analogues show interesting Michaelis–Menten constant (KM) in the mM range for the oxidant. Interestingly, the polymer structures are more resistant to denaturation (heat, proteolysis and oxidant concentration) than HRP, opening up interesting prospects for their use in catalysis or in biosensing devices.

过氧化物酶,如辣根过氧化物酶(HRP),是一种血红素金属酶,是各种氧化反应的强大生物催化剂。通过使用简单的接枝-从方法、开环聚合(ROP)和锰卟啉,成功制备了能够催化 H2O2 氧化反应的 HRP 星形多肽类似物。与它们的蛋白质模型一样,这些简化的类似物在氧化剂的毫摩尔范围内显示出有趣的迈克尔斯-门顿常数(KM)。有趣的是,这些聚合物结构比 HRP 更耐变性(热、蛋白水解和氧化剂浓度),这为它们在催化或生物传感设备中的应用开辟了有趣的前景。
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引用次数: 0
Enhanced Osteogenesis in 2D and 3D Culture Systems Using RGD Peptide and α-TCP Phase Transition within Alginate-Based Hydrogel 利用藻酸盐水凝胶中的 RGD 肽和α-TCP 相转变增强二维和三维培养系统中的骨生成。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-08 DOI: 10.1002/mabi.202400190
Jueun Kim, Yeong-Jin Choi, Chang-Woo Gal, Aram Sung, Siwi Setya Utami, Honghyun Park, Hui-suk Yun

Cell-laden hydrogels have been extensively investigated in various tissue engineering fields by their potential capacity to deposit numerous types of cells in a specific area. They are largely used in soft-tissue engineering applications because of their low mechanical strength. In addition, sodium alginate is well-known for its encapsulation, loading capacity and for being easily controllable; however, it lacks cell-binding ligands and hence the ability to adhere cells. In this study, it is aimed to enhance osteogenesis in cells encapsulated in alginate and improve its mechanical properties by introducing a synthetic peptide and calcium phosphate phase transition. To increase cell–hydrogel interactions and increasing cell viability, an RGD peptide is added to a photocrosslinkable methacrylate-modified alginate, and alpha-tricalcium phosphate (α-TCP) is added to the hydrogel to increase its mechanical strength via phase transition. Cell proliferation, growth, and differentiation are assessed in both 2D and 3D cell cultures. The addition of α-TCP significantly improved the mechanical properties of the hydrogel. Moreover, the RGD peptide and α-TCP showed a synergistic effect with significantly improved cell adhesion and osteogenesis in both 2D and 3D cell cultures. Therefore, the functional hydrogel developed in this study can potentially be used for bone tissue regeneration.

含细胞的水凝胶具有在特定区域沉积多种类型细胞的潜在能力,因此在各种组织工程领域得到了广泛的研究。由于它们的机械强度较低,因此主要用于软组织工程应用。此外,海藻酸钠以其封装性、负载能力和易于控制而闻名,但它缺乏细胞结合配体,因此无法粘附细胞。本研究旨在通过引入合成肽和磷酸钙相变,增强包裹在海藻酸钠中的细胞的成骨能力,并改善其机械性能。为了增加细胞与水凝胶之间的相互作用并提高细胞存活率,在可光交联的甲基丙烯酸甲酯改性海藻酸盐中加入了 RGD 肽,并在水凝胶中加入了α-磷酸三钙(α-TCP),通过相变提高水凝胶的机械强度。在二维和三维细胞培养中对细胞的增殖、生长和分化进行了评估。α-TCP的加入明显改善了水凝胶的机械性能。此外,RGD 肽和α-TCP 显示出协同效应,在二维和三维细胞培养中都能明显改善细胞粘附和成骨。因此,本研究开发的功能性水凝胶可用于骨组织再生。
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引用次数: 0
Hydrogels with Antioxidant Microparticles Systems Based on Hyaluronic Acid for Regenerative Wound Healing 基于透明质酸的抗氧化微颗粒水凝胶系统用于伤口再生愈合。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-05 DOI: 10.1002/mabi.202400153
Isabella Nacu, Alina Ghilan, Alina G. Rusu, Maria Bercea, Loredana E. Nita, Liliana Vereştiuc, Aurica P. Chiriac

This research focuses on the synthesis of hydrogels exhibiting enhanced antioxidant properties derived from hyaluronic acid (HA) and poly(ethylene brassylate-co-squaric acid) (PEBSA), a copolymacrolactone that have the ability to be used in drug delivery applications. Quercetin (Q), a bioflavonoid with strong antioxidant properties, is employed as a bioactive compound. The biomolecule is encapsulated in the polymeric network using different entrapment techniques, including the initial formation of a complex between PEBSA and Q, which is demonstrated through the dynamic light scattering technique. Fourier transform infrared spectroscopy (FT-IR) and rheological studies confirm the formation of the hydrogels, revealing the occurrence of physical interactions between the synthetic polymer and the polysaccharide. Moreover, the hydrogels demonstrate biocompatible properties after direct contact with the HDFa cell line and antioxidant properties, as revealed by DPPH tests.

本研究的重点是由透明质酸(HA)和聚(乙烯黄铜酸酯-共quaric酸)(PEBSA)(一种共聚高内酯)合成具有增强抗氧化性能的水凝胶,这种水凝胶可用于药物输送应用。槲皮素(Q)是一种生物类黄酮,具有很强的抗氧化性,被用作生物活性化合物。利用不同的包封技术将生物大分子包封在聚合物网络中,包括通过动态光散射技术证明 PEBSA 与 Q 之间最初形成的复合物。傅立叶变换红外光谱(FT-IR)和流变学研究证实了水凝胶的形成,揭示了合成聚合物和多糖之间存在物理相互作用。此外,水凝胶与 HDFa 细胞系直接接触后显示出生物相容性,DPPH 测试显示出抗氧化性。
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引用次数: 0
Fabrication of GelMA – Agarose Based 3D Bioprinted Photocurable Hydrogel with In Vitro Cytocompatibility and Cells Mirroring Natural Keratocytes for Corneal Stromal Regeneration 制作具有体外细胞相容性和天然角膜细胞镜像的基于琼脂糖的三维生物打印光固化水凝胶,用于角膜基质再生。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-03 DOI: 10.1002/mabi.202400136
Renuka Vijayaraghavan, Sravanthi Loganathan, Ravi Babu Valapa

The complex anatomy of the cornea and the subsequent keratocyte-fibroblast transition have always made corneal stromal regeneration difficult. Recently, 3D printing has received considerable attention in terms of fabrication of scaffolds with precise dimension and pattern. In the current work, 3D printable polymer hydrogels made of GelMA/agarose are formulated and its rheological properties are evaluated. Despite the variation in agarose content, both the hydrogels exhibited G′>G′′ modulus. A prototype for 3D stromal model is created using Solid Works software, mimicking the anatomy of an adult cornea. The fabrication of 3D-printed hydrogels is performed using pneumatic extrusion. The FTIR analysis speculated that the hydrogel is well crosslinked and established strong hydrogen bonding with each other, thus contributing to improved thermal and structural stability. The MTT analysis revealed a higher rate of cell proliferation on the hydrogels. The optical analysis carried out on the 14th day of incubation revealed that the hydrogels exhibit transparency matching with natural corneal stromal tissue. Specific protein marker expression confirmed the keratocyte phenotype and showed that the cells do not undergo terminal differentiation into stromal fibroblasts. The findings of this work point to the potential of GelMA/A hydrogels as a novel biomaterial for corneal stromal tissue engineering.

角膜复杂的解剖结构以及随后的角膜细胞-成纤维细胞转化过程一直给角膜基质再生带来困难。最近,3D 打印技术在制作具有精确尺寸和图案的支架方面受到了广泛关注。在当前的研究中,我们配制了由 GelMA/琼脂糖制成的可三维打印聚合物水凝胶,并对其流变特性进行了评估。尽管琼脂糖含量不同,但两种水凝胶都表现出 G'>G'' 模量。使用 Solid Works 软件模仿成人角膜的解剖结构创建了三维基质模型原型。三维打印水凝胶的制作采用气动挤出法。傅立叶变换红外光谱分析推测,水凝胶交联良好,相互之间建立了牢固的氢键,从而提高了热稳定性和结构稳定性。MTT 分析表明,水凝胶上的细胞增殖率更高。在培养的第 14 天进行的光学分析表明,水凝胶的透明度与天然角膜基质组织相匹配。特异性蛋白标记表达证实了角膜细胞的表型,并表明细胞不会最终分化为基质成纤维细胞。这项研究结果表明,GelMA/A 水凝胶有望成为角膜基质组织工程的新型生物材料。
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引用次数: 0
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Macromolecular bioscience
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