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Electrospun microfibers to enhance nutrient supply in bioinks and 3D-bioprinted tissue precursors. 电纺丝微纤维增强生物墨水和3d生物打印组织前体的营养供应。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-27 DOI: 10.1088/1758-5090/ad9d7a
A Neuhäusler, K Rogg, S Schröder, D Spiehl, H Zora, E Arefaine, J Schettler, H Hartmann, A Blaeser

3D-bioprinting is a promising technique to mimic the complex anatomy of natural tissues, as it comprises a precise and gentle way of placing bioinks containing cells and hydrogel. Although hydrogels expose an ideal growth environment due to their extracellular matrix (ECM)-like properties, high water amount and tissue like microstructure, they lack mechanical strength and possess a diffusion limit of a couple of hundred micrometers. Integration of electrospun fibers could hereby benefit in multiple ways, for instance by controlling mechanical characteristics, cell orientation, direction of diffusion and anisotropic swelling behavior. The aim of this study was to create an advanced ECM-biomimicking scaffold material for tissue engineering, which offers enhanced diffusion properties. PCL bulk membranes were successfully electrospun and fragmented using a cryo cutting technique. Subsequently, these short single fibers (<400µm in length and ∼5-10µm in diameter) were embedded in an agarose-based hydrogel after hydrophilization of the short single fibers by O2plasma treatment. Fiber-filled bioinks exhibit significantly improved biomolecule diffusion (>500µm), swelling properties (20%-60% of control), and higher mechanical strength, while its viscosity (5-30 mPas*s) and gelation kinetics (28 °C) remained almost unaffected. The diffusion tests indicate a high level of size selectivity, which can be utilized for targeted biomolecule transport in the future. Finally, applying 3D-bioprinting technology (drop-on-demand vs. microextrusion) a print setting dependent post-dispensing orientation of the fibers could be induced, which ultimately paves way for the fabrication of metamaterials with anisotropic material properties. As expected, the fiber-filled bioink was found to be non-cytotoxic in cell culture trials using HUVECs and HepG2 (>80% viability). In summary, microfiber integration holds great promise for 3D-bioprinting of tissue percursors with advanced metamaterial properties and thus offers high applicability in various fields of research, such asin-vitrotissue models, tissue engineered implants or cultivated meat.

3d生物打印是一种很有前途的技术,可以模拟自然组织的复杂解剖结构,因为它包含了一种精确而温和的方式来放置含有细胞和水凝胶的生物墨水。尽管水凝胶由于其细胞外基质(ECM)样特性、高含水量和组织样微观结构而暴露出理想的生长环境,但它们缺乏机械强度,并且具有几百微米的扩散极限。因此,电纺丝纤维的集成可以通过多种方式受益,例如通过控制机械特性、细胞取向、扩散方向和各向异性膨胀行为。本研究的目的是为组织工程创造一种先进的ecm仿生支架材料,该材料具有增强的扩散特性。利用低温切割技术成功地电纺丝和粉碎了PCL体膜。随后,这些短单纤维(500µm)、膨胀性能(对照组的20-60%)和更高的机械强度,而其粘度(5-30 mPas*s)和凝胶动力学(28°C)几乎没有受到影响。扩散试验表明其具有高水平的尺寸选择性,可用于未来的靶向生物分子运输。最后,应用3d生物打印技术(按需滴注与微挤出),可以诱导打印设置依赖于纤维的点胶后取向,最终为制造具有各向异性材料特性的超材料铺平道路。正如预期的那样,在使用HUVECs和HepG2 (bbb80 %存活率)进行的细胞培养试验中,发现纤维填充的生物链接是非细胞毒性的。综上所述,微纤维集成对于具有先进超材料特性的组织前体的3d生物打印具有很大的前景,因此在各种研究领域具有很高的适用性,例如体外组织模型,组织工程植入物或培养肉。
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引用次数: 0
Cell membrane-camouflaged nanoparticles activate fibroblast-myofibroblast transition to promote skin wound healing. 细胞膜伪装纳米颗粒激活成纤维细胞-肌成纤维细胞转化,促进皮肤伤口愈合。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-23 DOI: 10.1088/1758-5090/ad9cc4
Qi Jia, Yijuan Ding, Ziwen Su, Heying Chen, Jialing Ye, Dafeng Xie, Yubo Wu, Haiyan He, Yanlin Peng, Yilu Ni

The fibroblast-myofibroblast transition marked by extracellular matrix (ECM) secretion and contraction of actomyosin-based stress fibers, plays central roles in the wound healing process. This work aims to utilize the cell membrane-based nanoplatform to improve the outcomes of dysregulated wound healing. The cell membranes of myofibroblasts isolated from mouse skin are used as the camouflage for gold nanoparticles loaded with IL-4 cytokine. The membrane-modified nanoparticles show effective in situ clearance of bacterial infection, and act as the activator in IL-4Rα signaling pathway to induce pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype. Thus, the poor bacteria-clearance and non-stop inflammation in refractory wounds are improved and accelerated. Furthermore, the nanoplatform releases myofibroblast membranes to propel primitive fibroblasts toward the fibroblast-myofibroblast transition in an epigenetic manner. Matrix-production, vascularization, and epithelial regeneration are then initiated, leading to the satisfactory wound closure. Our study devises a new strategy for activating fibroblasts into myofibroblasts under prolonged and continuous exposure to the fibrotic environment, and develops a promising biomimetic nanoplatform for effective treatment of dysregulated chronic wound healing.

以细胞外基质(ECM)的分泌和肌动球蛋白为基础的应激纤维的收缩为标志的成纤维细胞-肌成纤维细胞转变在伤口愈合过程中起着核心作用。这项工作旨在利用基于细胞膜的纳米平台来改善失调伤口愈合的结果。从小鼠皮肤中分离出肌成纤维细胞的细胞膜,并用IL-4辅助细胞因子作为伪装包封金纳米颗粒。膜伪装纳米颗粒显示出对细菌感染的原位清除效果,并作为IL-4Rα信号通路的激活剂,诱导促炎M1亚型巨噬细胞向抗炎m2表型转变。从而改善和加速难治性伤口的细菌清除率差和持续炎症。接下来,纳米平台释放肌成纤维细胞膜,进一步推动原始成纤维细胞以表观遗传方式经历成纤维细胞-肌成纤维细胞的转变。然后开始基质生成、血管形成和上皮再生,导致令人满意的伤口愈合。我们的研究设计了一种新的策略,通过表观遗传修饰使成纤维细胞在长时间持续暴露于纤维化环境下转变为肌成纤维细胞,并开发了一种有前途的仿生纳米平台,用于有效治疗慢性伤口愈合失调。
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引用次数: 0
Modeling intratumor heterogeneity in breast cancer. 乳腺癌肿瘤内异质性的建模。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-19 DOI: 10.1088/1758-5090/ad9b50
Elizabeth McDonough, Margarida Barroso, Fiona Ginty, David T Corr

Reduced therapy response in breast cancer has been correlated with heterogeneity in biomarker composition, expression level, and spatial distribution of cancer cells within a patient tumor. Thus, there is a need for models to replicate cell-cell, cell-stromal, and cell-microenvironment interactions during cancer progression. Traditional two-dimensional (2D) cell culture models are convenient but cannot adequately represent tumor microenvironment histological organization,in vivo3D spatial/cellular context, and physiological relevance. Recently, three-dimensional (3D)in vitrotumor models have been shown to provide an improved platform for incorporating compositional and spatial heterogeneity and to better mimic the biological characteristics of patient tumors to assess drug response. Advances in 3D bioprinting have allowed the creation of more complex models with improved physiologic representation while controlling for reproducibility and accuracy. This review aims to summarize the advantages and challenges of current 3Din vitromodels for evaluating therapy response in breast cancer, with a particular emphasis on 3D bioprinting, and addresses several key issues for future model development as well as their application to other cancers.

乳腺癌治疗反应的降低与患者肿瘤内癌细胞的生物标志物组成、表达水平和空间分布的异质性有关。因此,需要模型来复制癌症进展过程中的细胞-细胞、细胞-基质和细胞-微环境相互作用。传统的二维(2D)细胞培养模型方便,但不能充分代表肿瘤微环境的组织学组织、体内三维空间/细胞背景和生理相关性。最近,三维(3D)体外肿瘤模型已被证明提供了一个改进的平台,以结合组成和空间异质性,并更好地模拟患者肿瘤的生物学特性,以评估药物反应。生物3D打印技术的进步使得在控制再现性和准确性的同时,可以创建更复杂的模型,并改善生理表征。本文旨在总结目前用于评估乳腺癌治疗反应的3D体外模型的优势和挑战,特别强调3D生物打印,并讨论未来模型开发及其在其他癌症中的应用的几个关键问题。
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引用次数: 0
Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy. 1型糖尿病治疗中强化血糖调节的工程孔富集和预血管化体积结构
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-16 DOI: 10.1088/1758-5090/ad998e
Jaewook Kim, In Kyong Shim, Yu Na Lee, Myungji Kim, Dong Gyu Hwang, Jihwan Kim, Yeonggwon Jo, Suhun Chae, Jisoo Kim, Song Cheol Kim, Dong-Woo Cho, Jinah Jang

Managing type 1 diabetes mellitus (T1DM) presents significant challenges because of the complexity of replicating the microenvironment of pancreatic islets and ensuring the long-term viability and function of transplanted insulin-producing cells (IPCs). This study developed a functional approach that utilizes 3D bioprinting technology to create pore-enriched and pre-vascularized tissue constructs incorporating a pancreatic tissue-derived decellularized extracellular matrix and human-induced pluripotent stem cells (hiPSCs) aimed at enhancing blood glucose regulation in T1DM. We designed a volumetric 3D pancreatic tissue construct that supported the engraftment, survival, and insulin-producing functionality of hiPSC-derived IPCs. The construct's porosity was optimized to enhance IPC delivery efficiency. Additionally, human umbilical vein endothelial cells co-cultured with IPCs in a patterned structure facilitated pre-vascularization, improving construct integration with host tissues and accelerating revascularization post-transplantation. Our results demonstrate high cell viability and sustained insulin production in diabetic rodent models, indicating the constructs' effectiveness in regulating blood glucose levels over an extended period. The findings of this study not only underscore the potential of 3D bioprinting for creating functional tissue constructs for T1DM treatment but also offer efficient cell delivery techniques applicable to other areas of regenerative medicine.

1型糖尿病(T1DM)的治疗面临着巨大的挑战,因为复制胰岛微环境和确保移植胰岛素生成细胞(IPCs)的长期生存能力和功能非常复杂。本研究开发了一种功能方法,利用3D生物打印技术,结合胰腺组织来源的脱细胞细胞外基质(pdECM)和人类诱导的多能干细胞(hiPSCs),创建孔隙富集和预血管化的组织结构,旨在增强T1DM患者的血糖调节。我们设计了一种体积三维胰腺组织结构(3D PTC),支持hipsc衍生的IPCs的植入、存活和胰岛素产生功能。优化了结构的孔隙度,以提高IPC的输送效率。此外,人脐静脉内皮细胞(HUVECs)与IPCs在模式结构中共同培养,促进了预血管形成,改善了构建体与宿主组织的整合,加速了移植后的血运重建。我们的研究结果在糖尿病啮齿动物模型中证明了高细胞活力和持续的胰岛素产生,表明该结构在长时间内调节血糖水平的有效性。这项研究的发现不仅强调了3D生物打印在为T1DM治疗创造功能性组织结构方面的潜力,而且还提供了适用于再生医学其他领域的高效细胞递送技术。
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引用次数: 0
Embedded 3D printing of engineered lung cancer model for assisting fine-needle aspiration biopsy. 用于辅助细针穿刺活检的工程肺癌模型的嵌入式3D打印。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-16 DOI: 10.1088/1758-5090/ad9fe0
Weijian Hua, Cheng Zhang, Lily Raymond, Kellen Mitchell, Kuo Xiao, Ryan Coulter, Erick Bandala, Manish Bishwokarma, Ying Yang, Danyang Zhao, Na Xiao, Yifei Jin

Lung cancer is a serious global health issue that requires the development of patient-specific, lung cancer model for surgical planning to train interventionalists and improve the accuracy of biopsies. Although the emergence of three-dimensional (3D) printing provides a promising solution to create customized models with complicated architectures, current 3D printing methods cannot accurately duplicate anatomical-level lung constructs with tumor(s) which are applicable for hands-on training and procedure planning. To address this issue, an embedded printing strategy is proposed to create respiratory bronchioles, blood vessels, and tumors in a photocurable yield-stress matrix bath. After crosslinking, a patient-specific lung cancer analogous model is produced, which has tunable transparency and mechanical properties to mimic lung parenchyma. This engineered model not only enables the practical training of fine-needle aspiration biopsy but also provides the necessary information, such as coordinates of aspiration, wound depth, and interference with surrounding tissues, for procedure optimization.

肺癌是一个严重的全球健康问题,需要开发针对患者的肺癌手术计划模型,以培训介入医师并提高活检的准确性。尽管三维(3D)打印的出现为创建具有复杂结构的定制模型提供了一个有希望的解决方案,但目前的3D打印方法不能准确地复制解剖级别的肿瘤肺结构,这些结构适用于实践培训和手术计划。为了解决这个问题,提出了一种嵌入式打印策略,在光固化屈服应力基质浴中创建呼吸细支气管、血管和肿瘤。交联后,产生了患者特异性肺癌模拟模型,该模型具有可调的透明度和机械性能,以模拟肺实质。该工程模型不仅可以实现细针穿刺活检的实践训练,还可以提供必要的信息,如穿刺坐标、伤口深度和与周围组织的干扰,以优化手术过程。
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引用次数: 0
3D printed PCL-nHAp composite implants for the treatment of segmental bone defects: in vivo application in a rabbit model. 3D打印PCL-nHAp复合植入物治疗节段性骨缺损:在兔模型中的体内应用
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-16 DOI: 10.1088/1758-5090/ad9fe1
Deniz Başöz, Muhammed İlkay Karaman, Senem Büyüksungur, Deniz Yucel, Nesrin Hasırcı, Barıs Kocaoglu, Vasif Hasirci

The management and treatment of long bone defects are challenging clinical problems. In this study, in order to address the need for load bearing segmental defects, 3D printed cylindrical implants of poly(-caprolactone) (PCL) and nanohydroxyapatite (nHAp) composites were prepared and applied as lateral segments to the femurs of New Zealand white rabbits. The results obtained after 6 weeks of implantation were compared with the autografts. Although the maximum load determined in the 3-point bending tests for the autografts (93±56 N) was higher than the composite implants (57±5 N), histological studies demonstrated similar new bone formation in both test groups. Also, a sizeable callus formation around the autografts and bone ingrowth to the 3D printed implants were observed, and X-ray studies confirmed the formation of the callus. An increase in the bone density around the defect site was detected for both test groups. SEM revealed close interaction between the newly formed bone tissue and the struts of the 3D printed implant. mRUST values, which is an indicator of tissue healing, increased continuously during 6 weeks. In conclusion, 3D printed, 1.5 cm long cylindrical nHAp-PCL implants exhibited excellent bone healing and biomechanical stability in the large lateral segmental bone defects of the rabbits even in a relatively short implantation time as 6 weeks. We believe that these implants could serve as an alternative to autografts in the treatment of long bone defects.

长骨缺损的管理和治疗是具有挑战性的临床问题。本研究针对负重节段缺损的需要,制备了3D打印聚(丙烯-己内酯)(PCL)和纳米羟基磷灰石(nHAp)复合材料的圆柱形植入物,作为新西兰大白兔股骨的外侧节段。将植入6周后的结果与自体移植物进行比较。虽然在三点弯曲试验中测定的最大载荷(93±56 N)高于复合种植体(57±5 N),组织学研究显示两组的新骨形成相似。此外,观察到自体移植物周围形成了相当大的愈伤组织,3D打印植入物的骨长入,x射线研究证实了愈伤组织的形成。在两个实验组中,缺损部位周围的骨密度都有所增加。扫描电镜显示了新形成的骨组织和3D打印植入物的支柱之间的密切相互作用。作为组织愈合指标的mRUST值在6周内持续升高。综上所述,3D打印的1.5 cm长圆柱形nHAp-PCL种植体即使在相对较短的植入时间(6周)内,也能在兔的大外侧节段骨缺损中表现出良好的骨愈合和生物力学稳定性。我们相信这些植入物可以作为自体移植物治疗长骨缺损的替代方法。
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引用次数: 0
An immunocompetent human kidney on-a-chip model to study renal inflammation and immune-mediated injury. 研究肾脏炎症和免疫介导损伤的免疫能力人肾芯片模型。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-16 DOI: 10.1088/1758-5090/ad9fdf
Linda Gijzen, Marleen Bokkers, Richa Hanamsagar, Thomas Olivier, Todd Burton, Laura Marlisa Tool, Mouly Fahrin Rahman, John Lowman, Virginia Savova, Terry K Means, Henriette L Lanz

Kidney damage and dysfunction is an emerging health issue worldwide resulting in high morbidity and mortality rates. Numerous renal diseases are recognized to be driven by the immune system. Despite this recognition, the development of targeted therapies has been challenging as knowledge of the underlying mechanism and complex interactions remains insufficient. Recent advancements in the field offer promising avenues for exploring the interplay between renal cells and immune cells and their role in the development of renal inflammation and diseases. This study describes the establishment of a human immunocompetent 3D in vitro co-culture model of the proximal tubule in a high-throughput microfluidic platform that can be used to study renal functionality and inflammatory processes. The model incorporated RPTEC in the top compartment and HUVECs in the bottom compartment cultured under flow and in direct contact with a collagen-I ECM gel resulting in the formation of polarized tubular structures. As an immune component, human primary monocytes of different donors were added to the lumen of the endothelium. Renal inflammation was successfully induced using complement activated serum (CAS) as evident by epithelial morphological changes, increased expression of adhesion molecules, release of pro-inflammatory cytokines, and reduced epithelial viability. Realtime migratory behavior of monocytes showed increased extravasation and migration towards the ECM and Renal compartment upon exposure to CAS with donor-to-donor differences observed. Finally, immune modulatory compounds showed efficacious inhibition of monocyte migration under inflammatory conditions in the microfluidic co-culture model. A successful co-culture model was established and can be applied to study renal functionality in health and disease but also for drug screening due to the compatibility of the platform with automation and relatively high throughput. Overall, the described proximal tubule model has high potential to fill the gap that currently exists to study renal inflammation preclinically. .

肾脏损害和功能障碍是全球范围内一个新兴的健康问题,导致高发病率和死亡率。许多肾脏疾病被认为是由免疫系统驱动的。尽管认识到这一点,但由于对潜在机制和复杂相互作用的了解仍然不足,靶向治疗的发展一直具有挑战性。该领域的最新进展为探索肾细胞和免疫细胞之间的相互作用及其在肾脏炎症和疾病发展中的作用提供了有希望的途径。本研究描述了在高通量微流控平台上建立人类近端小管免疫活性3D体外共培养模型,该模型可用于研究肾功能和炎症过程。该模型将RPTEC纳入顶部隔室,将HUVECs纳入底部隔室,在流动中培养,并与胶原- i ECM凝胶直接接触,形成极化管状结构。作为一种免疫成分,不同供体的人原代单核细胞被添加到内皮的管腔中。补体活化血清(CAS)成功诱导肾脏炎症,表现为上皮形态改变,粘附分子表达增加,促炎细胞因子释放,上皮活力降低。暴露于CAS后,单核细胞的实时迁移行为显示向ECM和肾室的外渗和迁移增加,供者与供者之间存在差异。最后,在微流体共培养模型中,免疫调节化合物显示出对炎症条件下单核细胞迁移的有效抑制。建立了一个成功的共培养模型,该模型不仅可以用于健康和疾病的肾功能研究,还可以用于药物筛选,因为该平台具有自动化兼容性和相对高的通量。总的来说,所描述的近端小管模型具有很大的潜力,可以填补目前临床前研究肾脏炎症的空白。 。
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引用次数: 0
High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myeloid leukemia. 骨髓性白血病药物测试中可重现的三维肿瘤微环境的高通量配方。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-16 DOI: 10.1088/1758-5090/ad998d
M Rudzinska-Radecka, L Turos-Korgul, D Mukherjee, P Podszywalow-Bartnicka, K Piwocka, J Guzowski

Leukemic microenvironment has been recognized as a factor that strongly supports the mechanisms of resistance. Therefore, targeting the microenvironment is currently one of the major directions in drug development and preclinical studies in leukemia. Despite the variety of available leukemia 3D culture models, the reproducible generation of miniaturized leukemic microenvironments, suitable for high-throughput drug testing, has remained a challenge. Here, we use droplet microfluidics to generate tens of thousands of highly monodisperse leukemic-bone marrow microenvironments within minutes. We employ gelatin methacryloyl (GelMA) as a model extracellular matrix (ECM) and tune the concentration of the biopolymer, check the impact of other components of the ECM (hyaluronic acid), cell concentration and the ratio of leukemic cells to bone marrow cells within the microbeads to establish the optimal conditions for microtissue formation. We administer model kinase inhibitor, imatinib, at various concentrations to the encapsulated leukemic microtissues, and, via comparing mono- and co-culture conditions (cancer alone vs cancer-stroma), we find that the stroma-leukemia crosstalk systematically protects the encapsulated cells against the drug-induced cytotoxicity. With that we demonstrate that our system mimics the physiological stroma-dependent protection. We discuss applicability of our model to (i) studying the role of direct- or close-contact interactions between the leukemia and bone marrow cells embedded in microscale 3D ECM on the stroma-mediated protection, and (ii) high-throughput screening of anti-cancer therapeutics in personalized leukemia therapies.

白血病微环境已被认为是支持耐药机制的一个重要因素。因此,靶向微环境是目前白血病药物开发和临床前研究的主要方向之一。尽管有多种可用的白血病3D培养模型,但适合高通量药物测试的小型化白血病微环境的可重复生成仍然是一个挑战。在这里,我们使用液滴微流体在几分钟内产生数万个高度单分散的白血病-骨髓微环境。我们采用明胶甲基丙烯酰(GelMA)作为模型细胞外基质(ECM),并调整生物聚合物的浓度,检查ECM(透明质酸)的其他成分的影响,细胞浓度和微珠内白血病细胞与骨髓细胞的比例,以建立微组织形成的最佳条件。我们将不同浓度的模型激酶抑制剂伊马替尼(imatinib)注射到被包裹的白血病微组织中,并通过比较单一和共培养条件(癌症单独与癌症基质),我们发现基质-白血病串扰系统地保护被包裹的细胞免受药物诱导的细胞毒性。由此,我们证明了我们的系统模拟了生理基质依赖性保护。我们讨论了我们的模型在以下方面的适用性:(i)研究嵌入在微尺度3D ECM中的白血病和骨髓细胞之间的直接或密切接触相互作用在基质介导的保护中的作用,以及(ii)在个性化白血病治疗中抗癌治疗的高通量筛选。
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引用次数: 0
3D printed PGCL@PLA/10CSPL composite scaffolds loaded with fibronectin 1 for intervertebral disc degeneration treatment. 3D打印加载纤维连接蛋白1 PGCL@PLA/10CSPL复合支架用于椎间盘退变治疗。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1088/1758-5090/ad998f
Weilin Zhang, Siyuan Chen, Shengbang Huang, Zhencong Li, Zhongwei Wang, Zhiwen Dai, Jinguo Liang, Hongrui Rong, Qianqian Ouyang, Weixiong Guo, Yen Wei, Jinsong Wei

Restoration of disc height and biomechanical function is essential for intervertebral disc degeneration (IDD) treatment. Removing abnormal nucleus pulposus (NP) tissue is an important step to facilitate bony fusion during the healing process. We analyzed publicly available single-cell transcriptome data for human normal and degenerative NP to identify genes associated with NP degeneration. A novel poly(glycolide-co-caprolactone)@polylactide (PLA)-b-aniline pentamer (AP)-b-PLA/chitosan-ϵ-polylysine (PGCL@1PAP/10CSPL) scaffold with good biocompatibility and electroactivity was designed and fabricated as an implant for IDD treatment using 3D printing technology. The PGCL@1PAP/10CSPL scaffold exhibited superior hydrophilicity, mechanical properties, cytocompatibility, and antibacterial activity compared to PGCL. Fibronectin 1 (FN1), identified from single-cell transcriptome analysis, was loaded into the PGCL@1PAP/10CSPL scaffold to accelerate the abnormal NP degeneration.In vitroandin vivoexperiments indicated that the PGCL@1PAP/10CSPL-FN1 scaffold enhanced osteogenic differentiation, promoted angiogenesis, and facilitated the removal of damaged disc tissue. This study introduces a novel implant system with desirable mechanical strength and unique bone-promoting and vascularizing properties for lumbar interbody fusion in IDD treatment.

恢复椎间盘高度和生物力学功能对于椎间盘退变(IDD)治疗至关重要。清除异常髓核组织是促进愈合过程中骨融合的重要一步。我们分析了公开的人类正常髓核和退化髓核的单细胞转录组数据,以确定与髓核退化相关的基因。我们设计了一种具有良好生物相容性和电活性的新型聚(乙二醇-共己内酯)@聚乳酸(PLA)-b-苯胺五聚体(AP)-b-PLA/壳聚糖-ϵ-聚赖氨酸(PGCL@1PAP/10CSPL)支架,并利用三维打印技术将其制作成一种用于治疗IDD的植入物。与 PGCL 相比,PGCL@1PAP/10CSPL 支架具有更优越的亲水性、机械性能、细胞相容性和抗菌活性。体外和体内实验表明,PGCL@1PAP/10CSPL-FN1 支架增强了成骨分化,促进了血管生成,并有助于移除受损的椎间盘组织。这项研究介绍了一种新型植入系统,它具有理想的机械强度和独特的促骨和血管生成特性,可用于腰椎间盘突出症(IDD)的腰椎椎间融合术治疗。
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引用次数: 0
Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening. 开发具有免疫功能的全层皮肤组织构建物来模拟皮肤纤维化,用于高通量药物筛选。
IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1088/1758-5090/ad998c
Yi Wei Lim, Russell Quinn, Kapil Bharti, Marc Ferrer, Hoda Zarkoob, Min Jae Song

The lack of the immune component in most of the engineered skin models remains a challenge to study the interplay between different immune and non-immune cell types of the skin. Immunocompetent humanin vitroskin models offer potential advantages in recapitulatingin vivolike behavior which can serve to accelerate translational research and therapeutics development for skin diseases. Here we describe a three-dimensional human full-thickness skin (FTS) equivalent incorporating polarized M1 and M2 macrophages from human peripheral CD14+monocytes. This macrophage-incorporated FTS model demonstrates discernible immune responses with physiologically relevant cytokine production and macrophage plasticity under homeostatic and lipopolysaccharide stimulation conditions. M2-incorporated FTS recapitulates skin fibrosis phenotypes with transforming growth factor-β1 treatment as reflected by significant collagen deposition and myofibroblast expression, demonstrating a M2 potentiation effect. In conclusion, we successfully biofabricated an immunocompetent FTS with functional macrophages in a high-throughput (HT) amenable format. This model is the first step towards a HT-assay platform to develop new therapeutics for skin diseases.

在大多数工程皮肤模型中缺乏免疫成分仍然是研究皮肤不同免疫和非免疫细胞类型之间相互作用的挑战。具有免疫能力的人体外皮肤模型在再现体内类似行为方面具有潜在的优势,可以加速皮肤疾病的转化研究和治疗开发。在这里,我们描述了一个3D人全层皮肤(FTS)等效物,其中包括来自人外周血CD14+单核细胞的极化M1和M2巨噬细胞。这种巨噬细胞结合的FTS模型显示,在稳态和脂多糖刺激条件下,具有明显的免疫反应,具有生理相关的细胞因子产生和巨噬细胞可塑性。M2-合并FTS重现了转化生长因子-β1处理后的皮肤纤维化表型,反映在显著的胶原沉积和肌成纤维细胞表达上,显示出M2增强效应。总之,我们成功地以高通量(HT)可适应的形式用功能性巨噬细胞生物制造了具有免疫能力的FTS。该模型是迈向ht检测平台的第一步,用于开发皮肤病的新疗法。
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