Materials Today Bio最新文献

The combination of hydrogels and rutin-loaded black phosphorus nanosheets treats rheumatoid arthritis 水凝胶与负载芦丁的黑磷纳米片的组合可治疗类风湿性关节炎

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-27 DOI: 10.1016/j.mtbio.2024.101264

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation, joint pain, and cartilage degradation. The fluctuating nature of RA often necessitates long-term oral administration of treatment drugs, which can unfortunately lead to adverse effects such as gastrointestinal discomfort and hepatic and renal dysfunction. Therefore, a percutaneous local delivery method for the release of inflammatory modulators in arthritic joints represents a promising therapeutic approach for RA. In this study, we have developed a unique and innovative therapeutic platform (named BP-Rut@Gel). This hydrogel was formulated by incorporating the drug Rutin (Rut) into Black phosphorus nanosheets (BP) and subsequently integrating them within a Hyaluronic Acid (HA) and Polyvinyl Alcohol (PVA) matrix to create a composite hydrogel. Notably, Secondly, photothermal therapy (PTT) under Near-Infrared Irradiation (NIR) and anti-inflammatory drugs synergistically worked together to efficiently quell inflammation and enhance therapeutic effectiveness. Additionally, toxicity experiments have revealed that our synthesized black phosphorus nanosheet composite hydrogel possesses excellent biocompatibility and significantly reduces the inflammatory response in RA joints. Given these remarkable properties, our BP-Rut@Gel hydrogel held significant promise and demonstrated immense clinical potential for the treatment of RA.

类风湿性关节炎（RA）是一种慢性炎症性自身免疫疾病，以炎症、关节疼痛和软骨退化为特征。由于类风湿性关节炎病情起伏不定，通常需要长期口服治疗药物，但不幸的是，这可能会导致胃肠道不适、肝肾功能障碍等不良反应。因此，在关节炎关节中释放炎症调节剂的经皮局部给药方法是一种很有前景的治疗方法。在这项研究中，我们开发了一种独特而创新的治疗平台（名为 BP-Rut@Gel）。这种水凝胶的配制方法是将药物芦丁（Rutin）加入黑磷纳米片（BP），然后将其融入透明质酸（HA）和聚乙烯醇（PVA）基质中，形成一种复合水凝胶。值得注意的是，其次，近红外照射下的光热疗法（PTT）与抗炎药物协同作用，可有效抑制炎症并提高疗效。此外，毒性实验表明，我们合成的黑磷纳米片复合水凝胶具有良好的生物相容性，能显著减轻 RA 关节的炎症反应。鉴于这些卓越的特性，我们的 BP-Rut@Gel 水凝胶在治疗 RA 方面具有重大的前景和巨大的临床潜力。

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引用次数: 0

Decellularized extracellular matrix-based disease models for drug screening 用于药物筛选的基于细胞外基质的脱细胞疾病模型

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-27 DOI: 10.1016/j.mtbio.2024.101280

In vitro drug screening endeavors to replicate cellular states closely resembling those encountered in vivo, thereby maximizing the fidelity of drug effects and responses within the body. Decellularized extracellular matrix (dECM)-based materials offer a more authentic milieu for crafting disease models, faithfully emulating the extracellular components and structural complexities encountered by cells in vivo. This review discusses recent advancements in leveraging dECM-based materials as biomaterials for crafting cell models tailored for drug screening. Initially, we delineate the biological functionalities of diverse ECM components, shedding light on their potential influences on disease model construction. Further, we elucidate the decellularization techniques and methodologies for fabricating cell models utilizing dECM substrates. Then, the article delves into the research strides made in employing dECM-based models for drug screening across a spectrum of ailments, including tumors, as well as heart, liver, lung, and bone diseases. Finally, the review summarizes the bottlenecks, hurdles, and promising research trajectories associated with the dECM materials for drug screening, alongside their prospective applications in personalized medicine. Together, by encapsulating the contemporary research landscape surrounding dECM materials in cell model construction and drug screening, this review underscores the vast potential of dECM materials in drug assessment and personalized therapy.

体外药物筛选致力于复制与体内细胞状态十分相似的细胞状态，从而最大限度地提高药物在体内作用和反应的真实性。基于脱细胞细胞外基质（dECM）的材料为制作疾病模型提供了更真实的环境，能忠实地模拟细胞外成分和细胞在体内遇到的复杂结构。这篇综述讨论了利用基于 dECM 的材料作为生物材料制作用于药物筛选的细胞模型的最新进展。首先，我们阐述了不同 ECM 成分的生物功能，揭示了它们对疾病模型构建的潜在影响。此外，我们还阐明了利用 dECM 基质制造细胞模型的脱细胞技术和方法。然后，文章深入探讨了利用基于 dECM 的模型进行药物筛选方面取得的研究进展，包括肿瘤、心脏、肝脏、肺部和骨骼疾病。最后，综述总结了用于药物筛选的 dECM 材料的瓶颈、障碍和有前景的研究轨迹，以及它们在个性化医疗中的应用前景。综上所述，本综述概括了围绕 dECM 材料在细胞模型构建和药物筛选方面的当代研究情况，强调了 dECM 材料在药物评估和个性化治疗方面的巨大潜力。

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引用次数: 0

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration 具有持续释放多柔比星功能的多巴胺功能化缺钙羟基磷灰石三维打印支架，用于骨肉瘤的协同化疗-光热疗法和加速骨再生

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-25 DOI: 10.1016/j.mtbio.2024.101253

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

骨组织内部再生和肿瘤切除后的快速复发是骨肉瘤和其他骨癌面临的严峻挑战。传统的骨组织工程支架缺乏对骨肿瘤复发的抑制作用。本文通过在缺钙羟基磷灰石（CDHA）支架表面自发聚合多巴胺（PDA），然后原位负载化疗药物多柔比星（DOX），设计出多功能支架（命名为 DOX/PDA@CDHA）。PDA 涂层赋予了支架显著的光热特性，而 DOX 的逐步释放则提供了有效的化疗效果。在双重刺激（近红外（NIR）光和肿瘤微环境中典型的酸性 pH 值）的触发下，DOX 在肿瘤部位按需释放，专门针对癌细胞，从而减轻了全身副作用。这些独特的特性有助于在体外和体内有效根除骨肉瘤。此外，该支架的组成模拟了天然骨骼的矿物相，并通过 PDA 的生物相容性得到了增强，从而促进了关键的成骨和血管生成过程。这不仅有利于消除肿瘤，还有利于健康骨组织的再生。总之，这项研究为骨肉瘤引起的骨缺损再生提供了一种有效的候选物质。

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引用次数: 0

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing 无定形磷酸锌纳米团簇负载聚碳酸酯热敏水凝胶：促进伤口愈合的创新策略

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-24 DOI: 10.1016/j.mtbio.2024.101266

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn²⁺ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

皮肤创伤是一个备受公众健康关注的问题，它强调了重建创伤部位微环境以促进组织再生的重要性。因此，研究创新型伤口敷料具有重要的研究和临床意义。在这项研究中，我们制备了一种基于亲水-疏水-亲水三嵌段聚碳酸酯聚合物（PTP）的热敏水凝胶，并通过加入无定形磷酸锌（AZP）纳米团簇制备了一种复合水凝胶 PTPH-AZP。我们评估了 PTPH-AZP 对人脐静脉内皮细胞（HUVECs）的影响以及促进皮肤伤口愈合的能力。结果发现，PTPH-AZP 在适当浓度下可通过持续释放 Zn2+ 促进 HUVEC 的增殖、迁移和管形成。体内实验表明，在伤口愈合的早期和中期阶段，PTPH-AZP 可促进伤口区域内血小板内皮细胞粘附分子-1（CD31）和α-平滑肌肌动蛋白（α-SMA）含量的增加，从而加速伤口的再上皮化和胶原沉积。在后期愈合阶段，PTPH-AZP 治疗组的表皮厚度明显改善，与周围完整皮肤一致，没有观察到衰减或增生性疤痕。体内研究结果表明，PTPH-AZP 可能对血管生成和伤口愈合有积极影响。总之，这项研究提出了一种很有前景的皮肤伤口愈合策略，凸显了 PTPH-AZP 作为一种有效治疗方法的潜力。

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引用次数: 0

Targeted regulation of autophagy using sorafenib-loaded biomineralization nanoenzyme for enhanced photodynamic therapy of hepatoma 利用装载索拉非尼的生物矿化纳米酶靶向调节自噬，增强肝癌的光动力疗法

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-24 DOI: 10.1016/j.mtbio.2024.101270

Sorafenib (SF), a multi-targeted tyrosine kinase inhibitor, serves as a primary therapeutic modality for advanced liver cancer. Nonetheless, its clinical efficacy is hindered by various obstacles, such as limited bioavailability and inadequate accumulation. This study introduces a novel biomimetic mineralization enzyme, known as BSA@Pt/Ce6/SF@M (PCFM). The PCFM incorporates platinum (Pt) as a catalytic agent, SF as a molecular-targeted therapeutic agent, and Ce6 as a photosensitizer within liver cancer cell membranes. This strategy enables the combination of various anti-tumor treatments, such as photodynamic therapy (PDT) and autophagy induction, leading to increased bioavailability of SF and achieving a multidimensional synergistic anticancer effect. The PDT effect produced by Ce6 in PCFM greatly enhances SF-induced autophagy, effectively promoting autophagic cell death. Furthermore, Pt dissociates from the biomineralization process, acquiring peroxidase properties through chemokinetic reactions. This facilitates the catalysis of significant oxygen generation, addressing the challenge of hypoxia in the tumor microenvironment and improving the efficacy of PDT. Moreover, the SF further enhances therapeutic efficacy by inducing autophagy in response to energy deprivation, as indicated by the reduced levels of HIF-1α, p62, along with increased levels of ROS and LC3-Ⅱ/Ι. This biomineralization-based nanoenzyme exhibits strong anti-tumor characteristics, offering a novel strategy for overcoming challenges in liver cancer treatment.

索拉非尼（Sorafenib）是一种多靶点酪氨酸激酶抑制剂，是晚期肝癌的主要治疗方法。然而，其临床疗效却受到生物利用度有限和蓄积不足等各种障碍的阻碍。本研究介绍了一种新型仿生矿化酶，即 BSA@Pt/Ce6/SF@M（PCFM）。PCFM 将铂 (Pt) 作为催化剂、SF 作为分子靶向治疗剂以及 Ce6 作为光敏剂结合到肝癌细胞膜中。这种策略能够将光动力疗法（PDT）和自噬诱导等多种抗肿瘤疗法结合起来，从而提高 SF 的生物利用率，实现多维协同抗癌效果。PCFM 中的 Ce6 产生的光动力疗法效应大大增强了 SF 诱导的自噬作用，有效促进了细胞的自噬死亡。此外，铂在生物矿化过程中解离，通过趋化反应获得过氧化物酶特性。这有利于催化大量氧气的生成，从而解决肿瘤微环境缺氧的难题，提高光动力疗法的疗效。此外，SF 还能通过诱导自噬来响应能量剥夺，从而进一步提高疗效，HIF-1α 和 p62 水平的降低以及 ROS 和 LC3-Ⅱ/Ι 水平的升高就说明了这一点。这种基于生物矿化的纳米酶具有很强的抗肿瘤特性，为克服肝癌治疗难题提供了一种新策略。

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引用次数: 0

Functionalized 3D-printed GelMA/Laponite hydrogel scaffold promotes BMSCs recruitment through osteoimmunomodulatory enhance osteogenic via AMPK/mTOR signaling pathway 功能化三维打印凝胶MA/皂石水凝胶支架通过AMPK/mTOR信号通路促进骨免疫调节增强成骨作用，从而促进BMSCs募集

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-23 DOI: 10.1016/j.mtbio.2024.101261

The migration and differentiation of bone marrow mesenchymal stem cells (BMSCs) play crucial roles in bone repair processes. However, conventional scaffolds often lack of effectively inducing and recruiting BMSCs. In our study, we present a novel approach by introducing a 3D-bioprinted scaffold composed of hydrogels, with the addition of laponite to the GelMA solution, aimed at enhancing scaffold performance. Both in vivo and in vitro experiments have confirmed the outstanding biocompatibility of the scaffold. Furthermore, for the first time, Apt19s has been chemically modified onto the surface of the hydrogel scaffold, resulting in a remarkable enhancement in the migration and adhesion of BMSCs. Moreover, the scaffold has demonstrated robust osteogenic differentiation capability in both in vivo and in vitro environments. Additionally, the hydrogel scaffold has shown the ability to induce the polarization of macrophages from M1 to M2, thereby facilitating the osteogenic differentiation of BMSCs via the bone immune pathway. Through RNA-seq analysis, it has been revealed that macrophages regulate the osteogenic differentiation of BMSCs through the AMPK/mTOR signaling pathway. In summary, the functionalized GelMA/Laponite scaffold offers a cost-effective approach for tailored in situ bone regeneration.

骨髓间充质干细胞（BMSCs）的迁移和分化在骨修复过程中起着至关重要的作用。然而，传统的支架往往不能有效诱导和招募骨髓间充质干细胞。在我们的研究中，我们提出了一种新方法，即引入一种由水凝胶组成的三维生物打印支架，并在 GelMA 溶液中添加青石，旨在提高支架的性能。体内和体外实验都证实了该支架出色的生物相容性。此外，Apt19s 首次被化学修饰到水凝胶支架表面，从而显著增强了 BMSCs 的迁移和粘附能力。此外，该支架在体内和体外环境中都表现出了强大的成骨分化能力。此外，水凝胶支架还能诱导巨噬细胞从 M1 极化为 M2，从而通过骨免疫途径促进 BMSCs 的成骨分化。通过 RNA-seq 分析发现，巨噬细胞通过 AMPK/mTOR 信号通路调控 BMSCs 的成骨分化。总之，功能化 GelMA/Laponite 支架为定制原位骨再生提供了一种经济有效的方法。

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引用次数: 0

Personalized PDAC chip with functional endothelial barrier for tumour biomarker detection: A platform for precision medicine applications 用于肿瘤生物标记物检测的具有功能性内皮屏障的个性化 PDAC 芯片：精准医疗应用平台

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-21 DOI: 10.1016/j.mtbio.2024.101262

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterised by poor survival rates and an increasing global incidence. Advances in the staging and categorization of pancreatic tumours, along with the discovery of functional mutations, have made precision treatments possible, which may lead to better clinical results. To further improve customized treatment approaches, in vitro models that can be used for functional drug sensitivity testing and precisely mimic the disease at the organ level are required. In this study, we present a workflow for creating a personalized PDAC chip utilising primary tumour-derived human pancreatic organoids (hPOs) and Human Umbilical Vein Endothelial Cells (HUVECs) to simulate the vascular barrier and tumour interactions within a PDMS-free organ-on-a-chip system. The patient PDAC tissue, expanded as tumour hPOs, could be cultured as adherent cells on the chip for more than 50 days, allowing continuous monitoring of cell viability through outflows from tumour and endothelial channels. Our findings demonstrate a gradual increase in cell density and cell turnover in the pancreatic tumor channel. Tumour-specific biomarkers, including CA-19.9, TIMP-1, Osteopontin, MIC-1, ICAM-1 and sAXL were consistently detected in the PDAC chip outflows. Comparative analyses between tissue culture plates and microfluidic conditions revealed significant differences in biomarker secretion patterns, highlighting the advantages of the microfluidics approach. This PDAC chip provides a stable, reproducible tumour model system with a functional endothelial cell barrier, suitable for drug sensitivity and secretory biomarker studies, thus serving as a platform for functional precision medicine application and multi-organ chip development.

胰腺导管腺癌（PDAC）是一种侵袭性很强的癌症，其特点是生存率低，全球发病率不断上升。胰腺肿瘤分期和分类方面的进展以及功能性突变的发现使精准治疗成为可能，这可能会带来更好的临床效果。为进一步改善定制化治疗方法，需要可用于功能性药物敏感性测试并在器官水平上精确模拟疾病的体外模型。在本研究中，我们介绍了一种创建个性化 PDAC 芯片的工作流程，利用原发肿瘤衍生的人胰腺器官组织（hPO）和人脐静脉内皮细胞（HUVEC）在不含 PDMS 的器官芯片系统中模拟血管屏障和肿瘤相互作用。作为肿瘤 hPOs 扩增的 PDAC 患者组织可以作为粘附细胞在芯片上培养 50 多天，从而可以通过肿瘤和内皮通道流出的细胞持续监测细胞活力。我们的研究结果表明，胰腺肿瘤通道中的细胞密度和细胞周转率逐渐增加。在 PDAC 芯片流出物中持续检测到肿瘤特异性生物标记物，包括 CA-19.9、TIMP-1、Osteopontin、MIC-1、ICAM-1 和 sAXL。组织培养板和微流控条件下的对比分析表明，生物标志物的分泌模式存在显著差异，这凸显了微流控方法的优势。该 PDAC 芯片提供了一个稳定、可重复的肿瘤模型系统，具有功能性内皮细胞屏障，适合药物敏感性和分泌型生物标记物研究，因此可作为功能性精准医学应用和多器官芯片开发的平台。

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引用次数: 0

Advances in studies on tracheal stent design addressing the related complications 针对相关并发症的气管支架设计研究取得进展

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-21 DOI: 10.1016/j.mtbio.2024.101263

Tracheal stents can be used to quickly reconstruct the airway and relieve symptoms of dyspnea in patients with tracheal stenosis. However, existing tracheal stents lead to complications such as granulation tissue formation, difficulty in removal, persistent growth of malignant tumors, stent migration, and mucus plugging. In this article, we reviewed the main methods used to reduce complications associated with tracheal stent design. Drug-eluting stents can inhibit granulation tissue formation and prevent infection and local chemotherapy. The biodegradable stent can support the trachea for some time, maintain tracheal patency, and degrade gradually, which avoids removing or replacing the stent. Radioactive stents loaded with I¹²⁵ have good potential for inhibiting the persistent growth of malignant tumors. Three-dimensional printing technology enables the manufacturing of patient-specific stents, which increases the degree of matching between the complex tracheal anatomy and the stent, thus providing a new solution for stent migration caused by structural mismatch. Minimizing the barrier of the stent to mucociliary clearance, providing an anti-fouling coating, and culturing respiratory epithelial cells on the surface of the stent are the main methods used to reduce mucus plugging. We also proposed future research directions for tracheal stents to guide the design and manufacture of ideal tracheal stents.

气管支架可用于快速重建气道，缓解气管狭窄患者的呼吸困难症状。然而，现有的气管支架会导致肉芽组织形成、移除困难、恶性肿瘤持续生长、支架移位和粘液堵塞等并发症。在本文中，我们回顾了用于减少气管支架设计相关并发症的主要方法。药物洗脱支架可抑制肉芽组织形成，防止感染和局部化疗。可降解支架可支撑气管一段时间，维持气管通畅，并逐渐降解，避免了支架的移除或更换。装载 I125 的放射性支架在抑制恶性肿瘤的持续生长方面具有良好的潜力。三维打印技术实现了患者专用支架的制造，提高了复杂气管解剖结构与支架的匹配度，从而为解决因结构不匹配导致的支架移位问题提供了新的解决方案。尽量减少支架对粘液纤毛清除的阻碍、提供防污涂层以及在支架表面培养呼吸道上皮细胞是减少粘液堵塞的主要方法。我们还提出了气管支架未来的研究方向，以指导理想气管支架的设计和制造。

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引用次数: 0

Injectable decellularized Wharton's jelly hydrogel containing CD56+ umbilical cord mesenchymal stem cell-derived exosomes for meniscus tear healing and cartilage protection 含有 CD56+ 脐带间充质干细胞衍生外泌体的可注射脱细胞沃顿果冻水凝胶，用于半月板撕裂愈合和软骨保护

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-19 DOI: 10.1016/j.mtbio.2024.101258

Traditional meniscectomy or suture for meniscal tear usually leads to failed self-healing, cartilage degeneration and worse osteoarthritis. The strategies that facilitate the healing process of torn meniscus and safeguard knee cartilage against degeneration will be promising for clinical therapy. The CD56⁺ umbilical cord mesenchymal stem cells (UCSCs) (CD56⁺UCSCs) were sorted from Wharton's jelly using flow cytometer. Then, the modified decellularized Wharton's Jelly hydrogel (DWJH) was combined with isolated CD56⁺Exos from CD56⁺UCSCs to fabricate DWJH/CD56⁺Exos. The in vitro studies were performed to characterize the DWJ (decellularized Wharton's Jelly). The injectability and rheological properties were assessed by shear rate and frequency sweep analysis. The biocompatibility and chondrogenic differentiation inducibility of DWJH/CD56⁺Exos were performed on human bone marrow mesenchymal stem cells (hBMSCs) and RAW 264.7 cells. The release dynamics was evaluated in vitro and in vivo experiments. As for the in vivo experiments, the operated rats that subjected to a 2 mm full-thickness longitudinal tear in right medial anterior meniscus were injected a single dose of DWJH/CD56⁺Exos. At 4 and 8 weeks postoperatively, torn meniscus healing and articular cartilage degeneration were evaluated by hematoxylin and eosin (H&E), safranin O/fast green (SO&FG), and Sirius red staining. In in vitro experiments, the injectable DWJH/CD56⁺Exos demonstrated excellent biocompatibility, exosome releasing efficiency, injectable property and chondrogenic inducibility. The results of in vivo experiments revealed that DWJH/CD56⁺Exos degraded over time, promoted meniscal chondrogenesis, organized meniscal extracellular matrix remodeling, safeguard articular cartilage and inhibited secondary cartilage degeneration, which accelerated further facilitated torn meniscus healing. The novel injectable DWJH/CD56⁺Exos promoted meniscal tear healing by promoting meniscal chondrogenesis, safeguarding articular cartilage, and inhibiting secondary cartilage degeneration.

传统的半月板切除术或半月板撕裂缝合术通常会导致半月板自愈失败、软骨退化和骨关节炎恶化。促进半月板撕裂愈合和保护膝关节软骨不退化的策略将在临床治疗中大有可为。利用流式细胞仪从沃顿果冻中分拣出 CD56+ 脐带间充质干细胞（UCSCs）（CD56+UCSCs）。然后，将改良的脱细胞沃顿果冻水凝胶（DWJH）与从 CD56+UCSCs 分离出的 CD56+Exos 结合，制成 DWJH/CD56+Exos。体外研究对脱细胞沃顿果冻水凝胶（DWJ）进行了表征。通过剪切速率和频率扫描分析评估了注射性和流变特性。在人骨髓间充质干细胞（hBMSCs）和 RAW 264.7 细胞上对 DWJH/CD56+Exos 的生物相容性和软骨分化诱导性进行了研究。在体外和体内实验中对释放动态进行了评估。在体内实验方面，对右侧内侧前半月板2毫米全厚纵向撕裂的手术大鼠注射单剂量的DWJH/CD56+Exos。术后4周和8周，用苏木精和伊红（H&E）、安全素O/快绿（SO&FG）和天狼星红染色法评估半月板撕裂愈合和关节软骨退化情况。在体外实验中，注射用DWJH/CD56+外泌体表现出良好的生物相容性、外泌体释放效率、可注射性和软骨诱导性。体内实验结果表明，DWJH/CD56+Exos可随时间降解，促进半月板软骨生成，组织半月板细胞外基质重塑，保护关节软骨，抑制继发性软骨变性，进一步加速半月板撕裂愈合。新型注射剂DWJH/CD56+Exos通过促进半月板软骨生成、保护关节软骨和抑制继发性软骨退化，促进半月板撕裂愈合。

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引用次数: 0

In vitro vascularization of 3D cell aggregates in microwells with integrated vascular beds 集成血管床的微孔中三维细胞聚集体的体外血管化

IF 8.7 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2024-09-19 DOI: 10.1016/j.mtbio.2024.101260

Most human tissues possess vascular networks supplying oxygen and nutrients. Engineering of functional tissue and organ models or equivalents often require the integration of artificial vascular networks. Several approaches, such as organs on chips and three-dimensional (3D) bioprinting, have been pursued to obtain vasculature and vascularized tissues in vitro. This technical feasibility study proposes a new approach for the in vitro vascularization of 3D microtissues. For this, we thermoform arrays of round-bottom microwells into thin non-porous and porous polymer films/membranes and culture vascular beds on them from which endothelial sprouting occurs in a Matrigel-based 3D extra cellular matrix. We present two possible culture configurations for the microwell-integrated vascular beds. In the first configuration, human umbilical vein endothelial cells (HUVECs) grow on and sprout from the inner wall of the non-porous microwells. In the second one, HUVECs grow on the outer surface of the porous microwells and sprout through the pores toward the inside. These approaches are extended to lymphatic endothelial cells. As a proof of concept, we demonstrate the in vitro vascularization of spheroids from human mesenchymal stem cells and MG-63 human osteosarcoma cells. Our results show the potential of this approach to provide the spheroids with an abundant outer vascular network and the indication of an inner vasculature.

大多数人体组织都拥有供应氧气和营养物质的血管网络。功能性组织和器官模型或等效模型的工程设计往往需要整合人工血管网络。目前已有多种方法，如芯片上的器官和三维（3D）生物打印，用于获取体外血管和血管化组织。这项技术可行性研究提出了一种三维微组织体外血管化的新方法。为此，我们将圆底微孔阵列热成型为薄的无孔和多孔聚合物薄膜/膜，并在其上培养血管床，在基于 Matrigel 的三维外细胞基质中，内皮从中萌发。我们介绍了微孔集成血管床的两种可能培养配置。在第一种配置中，人脐静脉内皮细胞（HUVEC）生长在无孔微孔的内壁上并从内壁发芽。在第二种配置中，人脐静脉内皮细胞（HUVEC）生长在多孔微孔的外表面，并通过孔隙向内发芽。这些方法已扩展到淋巴内皮细胞。作为概念验证，我们展示了人类间充质干细胞和 MG-63 人类骨肉瘤细胞球体的体外血管化。我们的研究结果表明，这种方法有可能为球体提供丰富的外层血管网络，并显示出内层血管。

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