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Silk Composite-Based Multifunctional Pellets for Controlled Release 基于蚕丝复合材料的多功能控释颗粒。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-20 DOI: 10.1002/mabi.202400410
Sushma Indrakumar, Sriram Bharath Gugulothu, Akshat Joshi, Tapan Kumar Dash, Vivek Mishra, Bharat Tandon, Kaushik Chatterjee

Chronic wounds present significant clinical challenges due to the high risk of infections and persistent inflammation. While personalized treatments in point-of-care settings are crucial, they are limited by the complex fabrication techniques of the existing products. The calcium sulfate hemihydrate (CSH)-based drug delivery platform enables rapid fabrication but lacks antioxidant and antibacterial properties, essential to promote healing. To develop a multifunctional platform, a tannic acid (TA)-silk fibroin (SF) complex is engineered and incorporated as an additive in CSH cement. This cement is then cast into pellets to create silk/bioceramic-based composite drug delivery systems, designed for point-of-care use. Compared to neat CSH pellets, the composite pellets exhibit a 7.5-fold increase in antioxidant activity and prolonged antibacterial efficacy (up to 13 d). Moreover, the subcutaneous implantation of the pellets shows no hallmarks of local or systemic toxicity in a rodent model. The pellets are optimized in composition and fabrication to ease market translation. Clinically, the pellets have the potential to be further developed into products to place on wound beds or fill into bone cavities that are designed to deliver the intended therapeutic effect. The developed multifunctional system proves to be a promising solution for personalized treatment in point-of-care settings.

由于感染和持续炎症的风险很高,慢性伤口给临床带来了巨大挑战。虽然护理点的个性化治疗至关重要,但现有产品复杂的制造技术限制了这种治疗。基于半水硫酸钙(CSH)的给药平台可以快速制造,但缺乏促进伤口愈合所必需的抗氧化和抗菌特性。为了开发多功能平台,我们设计了一种单宁酸(TA)-丝状纤维蛋白(SF)复合物,并将其作为添加剂加入半水硫酸钙水泥中。然后将这种水泥浇铸成颗粒,制成丝/生物陶瓷基复合给药系统,专供护理点使用。与纯 CSH 颗粒相比,复合颗粒的抗氧化活性提高了 7.5 倍,抗菌效力延长(长达 13 天)。此外,在啮齿动物模型中,皮下植入颗粒没有显示出局部或全身毒性。颗粒的成分和制造工艺均已优化,便于市场转化。在临床上,这种颗粒有可能进一步开发成产品,用于伤口床或填充骨腔,以达到预期的治疗效果。事实证明,所开发的多功能系统是在护理点环境下进行个性化治疗的一种很有前途的解决方案。
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引用次数: 0
Tunable Blended Collagen I/II and Collagen I/III Hydrogels as Tissue Mimics 作为组织模拟物的可调混合胶原 I/II 和胶原 I/III 水凝胶
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-20 DOI: 10.1002/mabi.202400280
Paulina M. Babiak, Carly M. Battistoni, Leonard Cahya, Rithika Athreya, Jason Minnich II, Alyssa Panitch, Julie C. Liu

Collagen (Col) is commonly used as a natural biomaterial for biomedical applications. Although Col I is the most prevalent col type employed, many collagen types work together in vivo to confer function and biological activity. Thus, blending collagen types can better recapitulate many native environments. This work investigates how hydrogel properties can be tuned through blending collagen types (col I/II and col I/III) and by varying polymerization temperatures. Col I/II results in poorly developed fibril networks, which softened the gels, especially at lower polymerization temperatures. Conversely, col I/III hydrogels exhibit well-connected fibril networks with localized areas of fine fibrils and result in stiffer hydrogels. A decreased molecular mass recovery rate is observed in blended hydrogels. The altered fibril morphologies, mechanical properties, and biological signals of the blended gels can be leveraged to alter cell responses and can be used as models for different tissue types (e.g., healthy vs fibrotic tissue). Furthermore, the biomimetic hydrogel properties are a tool that can be used to modulate the transport of drugs, nutrients, and wastes in tissue engineering applications.

胶原蛋白(Col)是生物医学应用中常用的天然生物材料。虽然Ⅰ型胶原蛋白是最常用的胶原蛋白类型,但许多胶原蛋白类型在体内共同作用,赋予人体功能和生物活性。因此,混合胶原类型可以更好地再现许多原生环境。这项工作研究了如何通过混合胶原类型(胶原 I/II 和胶原 I/III)和改变聚合温度来调整水凝胶的特性。Col I/II 导致纤维网络发育不良,从而软化了凝胶,尤其是在较低的聚合温度下。相反,Col I/III 水凝胶显示出连接良好的纤维网络,局部区域有细纤维,因此水凝胶较硬。在混合水凝胶中观察到分子质量恢复率降低。混合凝胶改变的纤维形态、机械性能和生物信号可用于改变细胞反应,并可用作不同组织类型(如健康组织与纤维化组织)的模型。此外,仿生水凝胶的特性还是一种工具,可用于调节组织工程应用中药物、营养物质和废物的运输。
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引用次数: 0
Molecules in Motion: Unravelling the Dynamics of Vascularization Control in Tissue Engineering. 运动中的分子:揭示组织工程中血管控制的动力学。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.1002/mabi.202400139
Francisco A. P. Rodrigues, Cláudia S. Oliveira, Simone C. Sá, Freni K. Tavaria, Sang Jin Lee, Ana L. Oliveira, João B. Costa

Significant progress has been made in tissue engineering (TE), aiming at providing personalized solutions and overcoming the current limitations of traditional tissue and organ transplantation. 3D bioprinting has emerged as a transformative technology in the field, able to mimic key properties of the natural architecture of the native tissues. However, most successes in the area are still limited to avascular or thin tissues due to the difficulties in controlling the vascularization of the engineered tissues. To address this issue, several molecules, biomaterials, and cells with pro- and anti-angiogenic potential have been intensively investigated. Furthermore, different bioreactors capable to provide a dynamic environment for in vitro vascularization control have been also explored. The present review summarizes the main molecules and TE strategies used to promote and inhibit vascularization in TE, as well as the techniques used to deliver them. Additionally, it also discusses the current challenges in 3D bioprinting and in tissue maturation to control in vitro/in vivo vascularization. Currently, this field of investigation is of utmost importance and may open doors for the design and development of more precise and controlled vascularization strategies in TE.

组织工程(TE)领域取得了重大进展,旨在提供个性化解决方案,克服传统组织和器官移植目前存在的局限性。三维生物打印技术已成为该领域的一项变革性技术,它能够模拟原生组织天然结构的关键特性。然而,由于难以控制工程组织的血管化,该领域的大多数成功案例仍局限于无血管或薄组织。为了解决这个问题,人们对一些具有促血管生成和抗血管生成潜能的分子、生物材料和细胞进行了深入研究。此外,人们还探索了能为体外血管生成控制提供动态环境的不同生物反应器。本综述总结了用于促进和抑制 TE 中血管生成的主要分子和 TE 策略,以及输送这些分子和策略的技术。此外,本综述还讨论了目前在三维生物打印和组织成熟过程中控制体外/体内血管化所面临的挑战。目前,这一研究领域极为重要,可能为设计和开发更精确、更可控的 TE 血管化策略打开大门。
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引用次数: 0
Bioengineered Silk Fibroin Hydrogel Reinforced with Collagen-Like Protein Chimeras for Improved Wound Healing 用胶原蛋白类嵌合体增强的生物工程蚕丝纤维素水凝胶可改善伤口愈合。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.1002/mabi.202400346
Thiagarajan Hemalatha, Mayilvahanan Aarthy, Ashokraj Sundarapandiyan, Niraikulam Ayyadurai

The study investigates the potentials of the rapid crosslinking hydrogel concoction comprising of natural silk fibroin (SF) and recombinant tailorable collagen-like protein with binding domains for wound repair. The formation of dityrosine crosslinks between the tyrosine moieties augments the formation of stable hydrogels, in the presence of the cytocompatible photo-initiator riboflavin and visible light. This uniquely engineered PASCH (Photo-activated silk fibroin and tailor-made collagen-like protein hydrogel) confers the key advantage of improved biological properties over the control hydrogels comprising only of SF. The physico-chemical characterization of the hydrogels with respect to crosslinking, modulus, and thermal stability delineates the ascendancy of PASCH 7:3 over other combinations. Furthermore, the hybrid protein hydrogel proves to be a favorable cellular matrix as it enhances cell adhesion, elongation, growth, and proliferation in vitro. Time-lapse microscopy studies reveal an enhanced wound closure in human endothelial cell monolayer (EA.hy926), while the gene expression studies portray the dynamic interplay of cytokines and growth factors in the wound milieu facilitating the repair and regeneration of cells, sculpted by the proteins. The results demonstrate the improved physical and biological properties of fabricated PASCH, depicting their synergism, and implying their competency for use in tissue engineering applications.

这项研究探讨了由天然蚕丝纤维素(SF)和具有结合域的重组可定制胶原蛋白样蛋白组成的快速交联水凝胶混合物在伤口修复方面的潜力。在细胞相容性光引发剂核黄素和可见光的作用下,酪氨酸分子之间形成的双酪氨酸交联可促进稳定水凝胶的形成。这种独特设计的 PASCH(光激活蚕丝纤维素和定制胶原蛋白水凝胶)与仅由蚕丝纤维素组成的对照水凝胶相比,具有改善生物特性的关键优势。水凝胶在交联、模量和热稳定性方面的物理化学特性表明,PASCH 7:3 比其他组合更具优势。此外,事实证明混合蛋白水凝胶是一种有利的细胞基质,因为它能增强体外细胞的粘附、伸长、生长和增殖。延时显微镜研究显示,人类内皮细胞单层(EA.hy926)的伤口闭合能力得到了增强,而基因表达研究则描绘了细胞因子和生长因子在伤口环境中的动态相互作用,促进了细胞在蛋白质雕刻下的修复和再生。研究结果表明,制造的 PASCH 具有更好的物理和生物特性,体现了它们之间的协同作用,并表明它们可用于组织工程应用。
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引用次数: 0
Proteins-Based Nanoparticles for Benznidazole Enteric Delivery 基于蛋白质的苯并咪唑肠道给药纳米颗粒
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-18 DOI: 10.1002/mabi.202400338
Victor A. Pilicita, Ana S. Sonzogni, Mariana Allasia, Florencia Borra, Roque J. Minari, Verónica D.G. Gonzalez

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects millions worldwide, particularly in Latin America. Despite its prevalence, treatment options remain limited. Current drugs, such as benznidazole, cause adverse effects possibly due to ineffective administration. In this context, nanoparticles offer a promising solution to target and control drug delivery by leading the effector site and minimizing side effects. This article focuses on zein-casein-based nanoparticles (Bioparticles, BP) coated with Eudragit L100-55 (BP:EU) for enteric delivery of benznidazole. BP:EU structures are synthesized to minimize premature drug release in the stomach, promoting release in the small intestine. Physical characterization confirmed the successful synthesis of BP:EU and their pH-responsive trigger for drug release. These findings suggest that this material can be a promising approach for Chagas disease treatment, addressing challenges in benznidazole delivery that can lead to improved therapeutic responses.

由克鲁斯锥虫(T. cruzi)引起的恰加斯病影响着全球数百万人,尤其是拉丁美洲人。尽管该病很普遍,但治疗方案仍然有限。目前的药物(如苯并咪唑)可能会因用药不当而产生不良反应。在这种情况下,纳米颗粒提供了一种很有前景的解决方案,通过引导作用部位来靶向和控制给药,并最大限度地减少副作用。本文重点研究了涂有 Eudragit L100-55 (BP:EU)的玉米蛋白-酪蛋白基纳米颗粒(Bioparticles,BP),用于苯并咪唑的肠道给药。合成 BP:EU 结构可最大限度地减少药物在胃中的过早释放,促进药物在小肠中的释放。物理表征证实了 BP:EU 的成功合成及其释放药物的 pH 响应触发器。这些研究结果表明,这种材料是治疗南美锥虫病的一种很有前景的方法,它解决了苯并咪唑给药方面的难题,从而提高了治疗效果。
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引用次数: 0
Exploiting the Potential of Decellularized Extracellular Matrix (ECM) in Tissue Engineering: A Review Study 在组织工程中开发脱细胞细胞外基质 (ECM) 的潜力:回顾研究。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-16 DOI: 10.1002/mabi.202400322
Peiman Brouki Milan, Farimah Masoumi, Esmaeil Biazar, Saeedeh Zare Jalise, Arezou Mehrabi

While significant progress has been made in creating polymeric structures for tissue engineering, the therapeutic application of these scaffolds remains challenging owing to the intricate nature of replicating the conditions of native organs and tissues. The use of human-derived biomaterials for therapeutic purposes closely imitates the properties of natural tissue, thereby assisting in tissue regeneration. Decellularized extracellular matrix (dECM) scaffolds derived from natural tissues have become popular because of their unique biomimetic properties. These dECM scaffolds can enhance the body's ability to heal itself or be used to generate new tissues for restoration, expanding beyond traditional tissue transfers and transplants. Enhanced knowledge of how ECM scaffold materials affect the microenvironment at the injury site is expected to improve clinical outcomes. In this review, recent advancements in dECM scaffolds are explored and relevant perspectives are offered, highlighting the development and application of these scaffolds in tissue engineering for various organs, such as the skin, nerve, bone, heart, liver, lung, and kidney.

虽然在为组织工程创造聚合物结构方面取得了重大进展,但由于复制天然器官和组织条件的复杂性,这些支架的治疗应用仍具有挑战性。将源自人体的生物材料用于治疗目的,可以近似地模仿天然组织的特性,从而帮助组织再生。源自天然组织的脱细胞细胞外基质(dECM)支架因其独特的生物模拟特性而广受欢迎。这些脱细胞细胞外基质支架可增强人体的自愈能力,或用于生成新的组织进行修复,超越了传统的组织转移和移植。加强对 ECM 支架材料如何影响损伤部位微环境的了解有望改善临床效果。本综述探讨了 dECM 支架的最新进展并提供了相关观点,重点介绍了这些支架在皮肤、神经、骨骼、心脏、肝脏、肺和肾脏等各种器官的组织工程中的开发和应用。
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引用次数: 0
Magnetically Active Bicontinuous Polymer Structures for Multiple Controlled Drug Delivery 用于多重可控给药的磁活性双连续聚合物结构
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-15 DOI: 10.1002/mabi.202470025
Elisa Lacroce, Fabio Pizzetti, Nicolás M. Barbosa Urrego, Giuseppe Nunziata, Maurizio Masi, Filippo Rossi

Back Cover: In article 2400084, Filippo Rossi and co-workers develop a magnetic bijel-like structure to load and release different types of molecules (hydrophilic and hydrophobic). The use of ε-caprolactone is explored, which can polymerize, forming hydrophobic domains (oil phase). After mixing with iron oxide nanoparticles (NPs), the water dispersion creates a magnetic biphasic porous structure without phase separation.

封底:在文章 2400084 中,Filippo Rossi 及其合作者开发了一种类似磁性 bijel 的结构,用于装载和释放不同类型的分子(亲水性和疏水性)。他们探索了ε-己内酯的使用,这种物质可以聚合,形成疏水域(油相)。在与氧化铁纳米粒子(NPs)混合后,水分散体会形成一种磁性双相多孔结构,且不会发生相分离。
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引用次数: 0
Mineralized Biopolymers-Based Scaffold Encapsulating with Dual Drugs for Alveolar Ridge Preservation 基于矿化生物聚合物的支架,包裹双重药物用于牙槽嵴保留。
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-15 DOI: 10.1002/mabi.202400351
Thanh-Han Hoang Tran, Cuong Hung Luu, Khanh-Tram Thi Nguyen, Mai-Anh Le Hoang, Quang-Khanh Pham, Chau My Phan, Nguyen-Kim-Luong Thai, Hieu Trung Nguyen, Thavasyappan Thambi, V.H. Giang Phan

Mineralization of scaffolds is essential for alveolar ridge preservation and bone tissue engineering, enhancing the mechanical strength and bioactivity of scaffolds, and promoting better integration with natural bone tissue. While the in situ mineralization method using concentrated SBF solutions is promising, there is limited comprehensive research on its effects. In this study, it is demonstrate that soaking gelatin/alginate scaffolds (GAS) in fivefold concentrated SBF significantly reduces the mineralization time to 3–7 days but also leads to considerable degradation and loss of the scaffold's original microstructure. The ratio of gelatin to alginate is optimized to improve the properties of GAS. The optimized GAS sample, when soaked in concentrated SBF to form GAS/HAp, exhibited hydroxyapatite (HAp) crystal formation starting from day 3, with mature hexagonal crystals forming by day 7. However, this process also caused significant decomposition and deformation of the scaffold's pore structure. Additionally, the biocompatibility of GAS and GAS/HAp is evaluated through in vitro, in ovo, haemolysis, and anti-ROS assays. The findings highlight the impact of SBF on the mineralization of GAS, laying the groundwork for further research in alveolar ridge preservation and bone tissue engineering.

支架的矿化对于牙槽嵴保存和骨组织工程至关重要,它能增强支架的机械强度和生物活性,促进与天然骨组织更好地融合。虽然使用浓缩 SBF 溶液进行原位矿化的方法很有前景,但对其效果的全面研究却很有限。本研究表明,将明胶/海藻酸盐支架(GAS)浸泡在五倍浓缩的 SBF 溶液中可将矿化时间显著缩短至 3-7 天,但同时也会导致相当程度的降解和支架原有微观结构的丧失。优化明胶与海藻酸盐的比例可改善 GAS 的性能。优化后的 GAS 样品在浓 SBF 中浸泡形成 GAS/HAp 后,从第 3 天开始出现羟基磷灰石(HAp)晶体形成,到第 7 天形成成熟的六方晶体。然而,这一过程也会导致支架孔隙结构发生明显的分解和变形。此外,还通过体外、体内、溶血和抗 ROS 检测评估了 GAS 和 GAS/HAp 的生物相容性。研究结果强调了 SBF5× 对 GAS 矿化的影响,为进一步研究牙槽嵴保存和骨组织工程奠定了基础。
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引用次数: 0
Injectable Photothermal PDA/Chitosan/β-Glycerophosphate Thermosensitive Hydrogels for Antibacterial and Wound Healing Promotion 用于抗菌和促进伤口愈合的可注射光热 PDA/壳聚糖/β-甘油磷酸酯热敏水凝胶
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-15 DOI: 10.1002/mabi.202470023
Dingkun Liu, Jinbing Chen, Linjuan Gao, Xing Chen, Liujun Lin, Xia Wei, Yuan Liu, Hui Cheng

Front Cover: In article 2400080, Hui Cheng and co-workers introduce a temperature-sensitive hydrogel with photothermal conversion capabilities. The cover shows how the hydrogel works. The temperature-sensitive hydrogel is injected to fill the entire wound, and then excited by near-infrared light, the hydrogel exerts a photothermal effect, raising the temperature to kill bacteria and ultimately promoting tissue healing.

封面:在文章 2400080 中,Hui Cheng 及其合作者介绍了一种具有光热转换功能的温敏水凝胶。封面展示了水凝胶的工作原理。将温敏水凝胶注入伤口,使其充满整个伤口,然后在近红外线的激发下,水凝胶产生光热效应,使温度升高以杀死细菌,最终促进组织愈合。
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引用次数: 0
Masthead: Macromol. Biosci. 10/2024 刊头:Macromol.Biosci.10/2024
IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-15 DOI: 10.1002/mabi.202470024
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引用次数: 0
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Macromolecular bioscience
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