Moon Sup Yoon, Jae Min Lee, Min Jeong Jo, Su Jeong Kang, Myeong Kyun Yoo, So Yeon Park, Ji-Hyun Kang, Chan-Su Park, Chun-Woong Park, Jin-Seok Kim, A. Bernardos, Vicente Martí-Centelles, Ramón Martínez-Máñez, Dae Hwan Shin
Three-dimensional bioprinting technology has opened new possibilities for nanoparticle evaluation. This review discusses the latest research trends using various disease models created through 3D bioprinting for biological evaluation of nanoparticles. The focus is on tumor models, vessel models, and skin models. In tumor models, evaluations include antitumor effects, gene expression analysis, and cytotoxicity comparisons between 2D and 3D models. Vessel models assess restenosis prevention, ischemic repair, and vascular regeneration. Skin models investigate nanoparticle toxicity, drug release, and transdermal penetration. These studies highlight the versatility of 3D bioprinting in replicating complex biological environments, enabling more accurate nanoparticle testing. The use of various bioinks and cell types enhances the relevance of in vitro findings. The integration of nanoparticles with 3D bioprinted models shows significant potential in advancing therapeutic strategies, including cancer treatment, vascular repair, and drug delivery systems. Overall, this comprehensive review underscores the importance of 3D bioprinting as an innovative platform for nanoparticle research, bridging the gap between traditional 2D cell cultures and in vivo studies, and contributing to the development of nanomedicines and personalized medical treatments, providing selected examples to illustrate the concepts.
{"title":"Advancements in 3D bioprinting for nanoparticle evaluation: Techniques, models, and biological applications","authors":"Moon Sup Yoon, Jae Min Lee, Min Jeong Jo, Su Jeong Kang, Myeong Kyun Yoo, So Yeon Park, Ji-Hyun Kang, Chan-Su Park, Chun-Woong Park, Jin-Seok Kim, A. Bernardos, Vicente Martí-Centelles, Ramón Martínez-Máñez, Dae Hwan Shin","doi":"10.36922/ijb.4273","DOIUrl":"https://doi.org/10.36922/ijb.4273","url":null,"abstract":"Three-dimensional bioprinting technology has opened new possibilities for nanoparticle evaluation. This review discusses the latest research trends using various disease models created through 3D bioprinting for biological evaluation of nanoparticles. The focus is on tumor models, vessel models, and skin models. In tumor models, evaluations include antitumor effects, gene expression analysis, and cytotoxicity comparisons between 2D and 3D models. Vessel models assess restenosis prevention, ischemic repair, and vascular regeneration. Skin models investigate nanoparticle toxicity, drug release, and transdermal penetration. These studies highlight the versatility of 3D bioprinting in replicating complex biological environments, enabling more accurate nanoparticle testing. The use of various bioinks and cell types enhances the relevance of in vitro findings. The integration of nanoparticles with 3D bioprinted models shows significant potential in advancing therapeutic strategies, including cancer treatment, vascular repair, and drug delivery systems. Overall, this comprehensive review underscores the importance of 3D bioprinting as an innovative platform for nanoparticle research, bridging the gap between traditional 2D cell cultures and in vivo studies, and contributing to the development of nanomedicines and personalized medical treatments, providing selected examples to illustrate the concepts.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141925315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Full-thickness skin injuries cause extended inflammation, compromised angiogenesis, and protracted wound healing, presenting considerable health risks. Herein, we introduce an innovative technique utilizing methacrylic anhydride (MA)-enhanced, one-step in-situ extrusion 3D bioprinting of collagen hydrogels, specifically engineered for the effective repair of full-thickness skin injuries. This method capitalizes on the inherent bioactivity of collagen, surmounting its mechanical constraints via a streamlined, one-step extrusion process enabled by MA. The resultant biomaterial ink, an optimized mix of collagen, MA, and photoinitiator, demonstrates superior printability, mechanical robustness, and stability, making it an ideal candidate for direct application onto wound sites. The bioprinted collagen scaffolds exhibit improved mechanical strength, reduced swelling, and enhanced resistance to enzymatic degradation, providing a durable matrix for cell proliferation and tissue in-growth. In vitro assessments reveal that the scaffolds support human foreskin fibroblast adhesion, proliferation, and migration, creating a conducive environment for skin regeneration. In vivo evaluations, conducted using a rat full-thickness skin injury model, further validate the scaffold's efficacy in promoting rapid and orderly tissue repair, characterized by accelerated re-epithelialization and organized collagen deposition. This MA-enhanced, in-situ extrusion 3D bioprinting technique generates collagen hydrogel scaffolds that significantly accelerate wound healing, offering promising advancements in tissue engineering and regenerative medicine.
全厚皮肤损伤会导致炎症扩大、血管生成受阻、伤口愈合时间延长，从而带来巨大的健康风险。在本文中，我们介绍了一种利用甲基丙烯酸酐（MA）增强型一步法原位挤压三维生物打印胶原蛋白水凝胶的创新技术，该技术专为有效修复全厚皮肤损伤而设计。这种方法利用了胶原蛋白固有的生物活性，通过甲基丙烯酸甲酯简化的一步挤压工艺，克服了胶原蛋白的机械限制。由此产生的生物材料墨水是胶原蛋白、MA 和光引发剂的优化组合，具有出色的可印刷性、机械坚固性和稳定性，是直接应用于伤口部位的理想选择。生物打印胶原支架具有更好的机械强度、更低的膨胀性和更强的抗酶降解能力，为细胞增殖和组织生长提供了持久的基质。体外评估显示，这种支架支持人类包皮成纤维细胞的粘附、增殖和迁移，为皮肤再生创造了有利环境。使用大鼠全厚皮肤损伤模型进行的体内评估进一步验证了该支架在促进快速有序的组织修复方面的功效，其特点是加速再上皮化和有组织的胶原沉积。这种 MA 增强型原位挤压三维生物打印技术生成的胶原蛋白水凝胶支架能显著加速伤口愈合，为组织工程和再生医学带来了巨大的进步。
{"title":"Methacrylic anhydride-assisted one-step in-situ extrusion 3D bioprinting of collagen hydrogels for enhanced full-thickness skin regeneration","authors":"Xiaxia Yang, Linyan Yao, Wenhua Li, Xiaodi Huang, Na Li, Jianxi Xiao","doi":"10.36922/ijb.4069","DOIUrl":"https://doi.org/10.36922/ijb.4069","url":null,"abstract":"Full-thickness skin injuries cause extended inflammation, compromised angiogenesis, and protracted wound healing, presenting considerable health risks. Herein, we introduce an innovative technique utilizing methacrylic anhydride (MA)-enhanced, one-step in-situ extrusion 3D bioprinting of collagen hydrogels, specifically engineered for the effective repair of full-thickness skin injuries. This method capitalizes on the inherent bioactivity of collagen, surmounting its mechanical constraints via a streamlined, one-step extrusion process enabled by MA. The resultant biomaterial ink, an optimized mix of collagen, MA, and photoinitiator, demonstrates superior printability, mechanical robustness, and stability, making it an ideal candidate for direct application onto wound sites. The bioprinted collagen scaffolds exhibit improved mechanical strength, reduced swelling, and enhanced resistance to enzymatic degradation, providing a durable matrix for cell proliferation and tissue in-growth. In vitro assessments reveal that the scaffolds support human foreskin fibroblast adhesion, proliferation, and migration, creating a conducive environment for skin regeneration. In vivo evaluations, conducted using a rat full-thickness skin injury model, further validate the scaffold's efficacy in promoting rapid and orderly tissue repair, characterized by accelerated re-epithelialization and organized collagen deposition. This MA-enhanced, in-situ extrusion 3D bioprinting technique generates collagen hydrogel scaffolds that significantly accelerate wound healing, offering promising advancements in tissue engineering and regenerative medicine.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingjing Chen, Qiuling Guo, Jinling Zhang, Ying Zhang, Yangxi Liu, Pengtao Wang, Chengzhu Zhao, Linda F Bonewald, Xiaolin Tu
3D bioprinting is a focused field in orthopedics, and its application with physiological osteogenic microenvironments (POME) is a prerequisite for authentic bone reconstruction. Mechanical stimulation produces PGE2 in mechanosensory osteocytes, but it is still unclear whether osteocytic PGE2 is a POME. PGE2 is an inducer of osteogenesis by acting on bone marrow stromal cells through its receptors EP2/EP4 to initiate osteogenic differentiation and mineralization. Unfortunately, clinical trials of PGE2 have shown side effects, including fever and drowsiness, so targeting the PGE2 receptor on specific tissues can avoid side effects. Here, we show that MLO-Y4 osteocytes treated with EP2/EP4 agonists for 24 h develop the functions of promoting osteogenic differentiation and mineralization while inhibiting adipogenesis of the stromal cell line ST2 and inducing tubule formation and angiogenic marker expression in HUVEC cells. Mechanistically, activation of the PGE2 signaling pathway in osteocytes appears to have autocrine effects by inducing the expression of the EP2 and EP4 receptors and COX-2 (Ptgs2), further auto-amplifying PGE2 signaling. PGE2 produced by the treated MLO-Y4 cells appears responsible for osteogenesis in addition to other unknown factors. MLO-Y4 and ST2 cells were incorporated into POME 3D constructs with greater than 95% viability within 7 days. Treatment of osteocytes with a PGE2 receptor agonist lineally proliferates ST2 cells, enhances the expression of osteoblast markers and mineralization. Due to 3D bioprinting being the closest model to in vivo research, these data showed that osteocytic PGE2 receptor signaling is a safe and mild POME with great potential for translational applications.
{"title":"Osteocytic PGE2 receptors EP2/4 signaling create a physiological osteogenic microenvironment in polycaprolactone 3D module","authors":"Jingjing Chen, Qiuling Guo, Jinling Zhang, Ying Zhang, Yangxi Liu, Pengtao Wang, Chengzhu Zhao, Linda F Bonewald, Xiaolin Tu","doi":"10.36922/ijb.3959","DOIUrl":"https://doi.org/10.36922/ijb.3959","url":null,"abstract":"3D bioprinting is a focused field in orthopedics, and its application with physiological osteogenic microenvironments (POME) is a prerequisite for authentic bone reconstruction. Mechanical stimulation produces PGE2 in mechanosensory osteocytes, but it is still unclear whether osteocytic PGE2 is a POME. PGE2 is an inducer of osteogenesis by acting on bone marrow stromal cells through its receptors EP2/EP4 to initiate osteogenic differentiation and mineralization. Unfortunately, clinical trials of PGE2 have shown side effects, including fever and drowsiness, so targeting the PGE2 receptor on specific tissues can avoid side effects. Here, we show that MLO-Y4 osteocytes treated with EP2/EP4 agonists for 24 h develop the functions of promoting osteogenic differentiation and mineralization while inhibiting adipogenesis of the stromal cell line ST2 and inducing tubule formation and angiogenic marker expression in HUVEC cells. Mechanistically, activation of the PGE2 signaling pathway in osteocytes appears to have autocrine effects by inducing the expression of the EP2 and EP4 receptors and COX-2 (Ptgs2), further auto-amplifying PGE2 signaling. PGE2 produced by the treated MLO-Y4 cells appears responsible for osteogenesis in addition to other unknown factors. MLO-Y4 and ST2 cells were incorporated into POME 3D constructs with greater than 95% viability within 7 days. Treatment of osteocytes with a PGE2 receptor agonist lineally proliferates ST2 cells, enhances the expression of osteoblast markers and mineralization. Due to 3D bioprinting being the closest model to in vivo research, these data showed that osteocytic PGE2 receptor signaling is a safe and mild POME with great potential for translational applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitsuyuki Hidaka, Masaru Kojima, Colin Zhang, Yasunori Okano, Shinji Sakai
Three-dimensional (3D) bioprinting has emerged as a promising technology in the field of tissue engineering. Notably, the advancement of multi-ink printing technology is crucial for further progress in 3D bioprinting. In this study, we developed a single-nozzle system with multiple inlets for multi-ink bioprinting that achieves high switching efficiency through a combination of numerical and experimental approaches. This single-nozzle system demonstrates the potential for higher-resolution printing and quicker ink switching compared with multi-nozzle printing systems. In general, inks used in bioprinting have low viscosity (<10 Pa・s); however, their behaviors inside a single nozzle have not been thoroughly investigated. Initially, we conducted numerical simulations to analyze fluid behavior within single nozzles, focusing on the junction of multiple ink inlets, to propose an advanced nozzle design. We proposed a novel index, Se, for evaluating the switching behavior of the bioink inside the single nozzle. Numerical simulation results showed that the nozzle design and combinations of inks affected Se. In addition, subsequent experimental analysis confirmed the consistency of the simulation results. The proposed design, developed using simulations, featured a single nozzle with enhanced switching efficiency, demonstrating a smaller transition length compared with that of conventional single nozzles or T-junction nozzles in printing line structures of different viscous inks. This is the first study to employ numerical simulation in designing a single nozzle with multiple inlets to switch ink in multi-ink bioprinting. This methodology will broaden the potential of single nozzles for high-resolution printing in bioprinting applications.
三维（3D）生物打印已成为组织工程领域一项前景广阔的技术。值得注意的是，多墨水打印技术的进步对于三维生物打印技术的进一步发展至关重要。在本研究中，我们开发了一种用于多墨水生物打印的多入口单喷嘴系统，该系统通过数值和实验相结合的方法实现了高切换效率。与多喷嘴打印系统相比，这种单喷嘴系统具有打印分辨率更高、墨水切换更快的潜力。一般来说，用于生物打印的油墨粘度较低（<10 Pa﹒s）；然而，它们在单喷嘴内的行为尚未得到深入研究。最初，我们进行了数值模拟，分析了单个喷嘴内的流体行为，重点是多个墨水入口的交界处，从而提出了先进的喷嘴设计方案。我们提出了一个新指标 Se，用于评估生物墨水在单喷嘴内的切换行为。数值模拟结果表明，喷嘴设计和油墨组合会影响 Se。此外，随后的实验分析也证实了模拟结果的一致性。利用模拟开发的拟议设计具有单喷嘴的特点，可提高切换效率，在不同粘性油墨的印刷生产线结构中，与传统的单喷嘴或 T 型接合喷嘴相比，过渡长度更小。这是首次在多墨水生物打印中使用数值模拟来设计具有多个入口的单喷嘴以切换墨水的研究。这种方法将拓宽单喷嘴在生物打印应用中进行高分辨率打印的潜力。
{"title":"Experimental and numerical approaches for optimizing conjunction area design to enhance switching efficiency in single-nozzle multi-ink bioprinting systems","authors":"Mitsuyuki Hidaka, Masaru Kojima, Colin Zhang, Yasunori Okano, Shinji Sakai","doi":"10.36922/ijb.4091","DOIUrl":"https://doi.org/10.36922/ijb.4091","url":null,"abstract":"Three-dimensional (3D) bioprinting has emerged as a promising technology in the field of tissue engineering. Notably, the advancement of multi-ink printing technology is crucial for further progress in 3D bioprinting. In this study, we developed a single-nozzle system with multiple inlets for multi-ink bioprinting that achieves high switching efficiency through a combination of numerical and experimental approaches. This single-nozzle system demonstrates the potential for higher-resolution printing and quicker ink switching compared with multi-nozzle printing systems. In general, inks used in bioprinting have low viscosity (<10 Pa・s); however, their behaviors inside a single nozzle have not been thoroughly investigated. Initially, we conducted numerical simulations to analyze fluid behavior within single nozzles, focusing on the junction of multiple ink inlets, to propose an advanced nozzle design. We proposed a novel index, Se, for evaluating the switching behavior of the bioink inside the single nozzle. Numerical simulation results showed that the nozzle design and combinations of inks affected Se. In addition, subsequent experimental analysis confirmed the consistency of the simulation results. The proposed design, developed using simulations, featured a single nozzle with enhanced switching efficiency, demonstrating a smaller transition length compared with that of conventional single nozzles or T-junction nozzles in printing line structures of different viscous inks. This is the first study to employ numerical simulation in designing a single nozzle with multiple inlets to switch ink in multi-ink bioprinting. This methodology will broaden the potential of single nozzles for high-resolution printing in bioprinting applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Yeung, Chi-Yeung Mang, Quan-Jing Mei, Chi Ho Wong, Chak-Yin Tang, Xin Zhao, Wing-Cheung Law, G. Tsui, Zhenjia Huang
This paper introduces a mathematical approach and additive manufacturing process to customize the mechanical properties of sheet gyroid bioscaffolds and mimicking the intricate architecture of natural bone. By defining the parameters of the level-set equation, scaffolds with spatially controlled porosity and anisotropic properties can be fabricated though digital light processing and microwave heating. A new susceptor-assisted hybrid pyrolysis-sintering process was developed, resulting in a significant enhancement in quality and mechanical properties of the three-dimensional (3D)-printed ceramic compared to conventional methods. The enhancements are originated from the improved densification, accelerated sintering kinetics, promotion of cristobalite phase transformation, and reduced defect volume under microwave heating. Sheet gyroid scaffolds with radially graded porosity and anisotropic properties were fabricated. Despite the porosity distribution, an increase in the unit cell’s aspect ratio amplified the anisotropic mechanical properties. This was also accompanied by a slight decrease in cell proliferation efficiency possibly due to variations in Gaussian curvatures.
{"title":"Design and fabrication of anisotropic SiO2 gyroid bioscaffolds with tunable properties","authors":"K. Yeung, Chi-Yeung Mang, Quan-Jing Mei, Chi Ho Wong, Chak-Yin Tang, Xin Zhao, Wing-Cheung Law, G. Tsui, Zhenjia Huang","doi":"10.36922/ijb.3609","DOIUrl":"https://doi.org/10.36922/ijb.3609","url":null,"abstract":"This paper introduces a mathematical approach and additive manufacturing process to customize the mechanical properties of sheet gyroid bioscaffolds and mimicking the intricate architecture of natural bone. By defining the parameters of the level-set equation, scaffolds with spatially controlled porosity and anisotropic properties can be fabricated though digital light processing and microwave heating. A new susceptor-assisted hybrid pyrolysis-sintering process was developed, resulting in a significant enhancement in quality and mechanical properties of the three-dimensional (3D)-printed ceramic compared to conventional methods. The enhancements are originated from the improved densification, accelerated sintering kinetics, promotion of cristobalite phase transformation, and reduced defect volume under microwave heating. Sheet gyroid scaffolds with radially graded porosity and anisotropic properties were fabricated. Despite the porosity distribution, an increase in the unit cell’s aspect ratio amplified the anisotropic mechanical properties. This was also accompanied by a slight decrease in cell proliferation efficiency possibly due to variations in Gaussian curvatures. ","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioimaging is used to inspect the successful growth and functional differentiation of cells in printed biomaterials, which are ultimately finalized into functional artificial tissues capable of replacing native tissues. While optical bioimaging techniques are commonly utilized, the current trend in three-dimensional (3D) bioprinting towards replicating complex 3D microarchitectures poses a challenge for conventional optical imaging techniques in providing clear cross-sectional images due to the opaque nature of tissue. Consequently, these limitations necessitate lengthy and destructive preparation processes, which are associated with sacrificing cell viability and damaging the bioprinted material. Photoacoustic imaging (PAI) is a versatile imaging technique that extends the advantages of the optical bioimaging technique to undiscovered depths enabled by its acoustic hybridity, making itself a promising tool for non-destructive imaging of 3D bioprinted constructs. In this review, we introduce the flexible spectral contrasts provided by PAI, which are potentially applicable to 3D-bioprinted constructs, and summarize bioprinting studies that functionally implement PAI for in vitro and in vivo assessments. Finally, we provide an outlook on practical considerations for the more complete integration of these two fields, anticipating more fruitful discoveries as bioprinting advances towards more complex hierarchies.
生物成像技术用于检测细胞在打印生物材料中的成功生长和功能分化，最终形成能够替代原生组织的功能性人工组织。虽然光学生物成像技术得到了普遍应用，但由于组织的不透明性，目前三维（3D）生物打印的趋势是复制复杂的三维微结构，这给传统光学成像技术提供清晰的横截面图像带来了挑战。因此，这些局限性使得制备过程既漫长又具有破坏性，既牺牲细胞活力又损坏生物打印材料。光声成像（PAI）是一种多功能成像技术，它将光学生物成像技术的优势扩展到了声学混合性所带来的未发现的深度，使其本身成为一种对三维生物打印构建体进行非破坏性成像的有前途的工具。在这篇综述中，我们介绍了 PAI 提供的灵活的光谱对比度，这种对比度可能适用于三维生物打印构建体，并总结了将 PAI 功能用于体外和体内评估的生物打印研究。最后，我们展望了这两个领域更全面整合的实际考虑因素，预计随着生物打印技术向更复杂的层次结构发展，将会有更多富有成果的发现。
{"title":"Photoacoustic imaging for three-dimensional bioprinted constructs","authors":"Donghyeon Oh, H. Choi, Chulhong Kim, Jinah Jang","doi":"10.36922/ijb.3448","DOIUrl":"https://doi.org/10.36922/ijb.3448","url":null,"abstract":"Bioimaging is used to inspect the successful growth and functional differentiation of cells in printed biomaterials, which are ultimately finalized into functional artificial tissues capable of replacing native tissues. While optical bioimaging techniques are commonly utilized, the current trend in three-dimensional (3D) bioprinting towards replicating complex 3D microarchitectures poses a challenge for conventional optical imaging techniques in providing clear cross-sectional images due to the opaque nature of tissue. Consequently, these limitations necessitate lengthy and destructive preparation processes, which are associated with sacrificing cell viability and damaging the bioprinted material. Photoacoustic imaging (PAI) is a versatile imaging technique that extends the advantages of the optical bioimaging technique to undiscovered depths enabled by its acoustic hybridity, making itself a promising tool for non-destructive imaging of 3D bioprinted constructs. In this review, we introduce the flexible spectral contrasts provided by PAI, which are potentially applicable to 3D-bioprinted constructs, and summarize bioprinting studies that functionally implement PAI for in vitro and in vivo assessments. Finally, we provide an outlook on practical considerations for the more complete integration of these two fields, anticipating more fruitful discoveries as bioprinting advances towards more complex hierarchies.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141812127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Dong Koo, Min-Hee Kang, Dahong Kim, Min Jeong Cho, Yu Jin Kim, JuYi Jang, Seon Ju Yeo, Geehong Kim, Su A Park, Jae Ho Lee
Oviducts have specific biomechanical properties that support fertilization and preimplantation embryo development, both of which are essential for successful pregnancy. However, conventional plastic-based human embryo culture does not recapitulate the biomechanical environment of the oviduct. Therefore, oviduct mimic culture systems that accurately emulate biophysical conditions for reproductive cells are a significant unmet clinical need. In the present study, we designed a three-dimensional (3D)-bioprinted optimal soft hydrogel system that accurately mimics the oviduct environment and investigated signaling factors during embryo development. We developed an oviduct tube-mimic hydrogel culture dish using gelatin methacryloyl (GelMA) 3D-bioprinted hydrogel. Quantitative assessment of hydrogel mechanical properties depended on the stiffness of the GelMA 3D-bioprinted hydrogel. Embryo quality was evaluated based on cleavage speed and blastocyst ratio on the GelMA hydrogel. Whole-transcriptome next-generation sequencing (NGS) analysis of embryos was used to identify biomechanical signaling factors. Our findings revealed that 10 kPa GelMA hydrogel culture conditions performed better with respect to development speed, blastocyst ratio, and hatching ratio than the control condition. Whole transcriptome NGS revealed up-regulation of mRNA processing genes and protein transport genes by the 7 and 10 kPa hydrogels. Furthermore, the inner cell mass and the number of Oct4+ cells were significantly higher in blastocysts cultured on 10 kPa hydrogel dishes than in those cultured on conventional hard plastic dishes. These findings demonstrate that optimized oviduct-mimic hydrogel-based 3D GelMA culture dishes could improve in vitro embryo development. Hence, 3D GelMA culture dishes may be useful as human embryo culture systems for assisted reproductive techniques.
{"title":"3D-bioprinted gelatin methacryloyl hydrogel culture system emulating the oviduct environment for enhanced preimplantation embryo development","authors":"Yun Dong Koo, Min-Hee Kang, Dahong Kim, Min Jeong Cho, Yu Jin Kim, JuYi Jang, Seon Ju Yeo, Geehong Kim, Su A Park, Jae Ho Lee","doi":"10.36922/ijb.3346","DOIUrl":"https://doi.org/10.36922/ijb.3346","url":null,"abstract":"Oviducts have specific biomechanical properties that support fertilization and preimplantation embryo development, both of which are essential for successful pregnancy. However, conventional plastic-based human embryo culture does not recapitulate the biomechanical environment of the oviduct. Therefore, oviduct mimic culture systems that accurately emulate biophysical conditions for reproductive cells are a significant unmet clinical need. In the present study, we designed a three-dimensional (3D)-bioprinted optimal soft hydrogel system that accurately mimics the oviduct environment and investigated signaling factors during embryo development. We developed an oviduct tube-mimic hydrogel culture dish using gelatin methacryloyl (GelMA) 3D-bioprinted hydrogel. Quantitative assessment of hydrogel mechanical properties depended on the stiffness of the GelMA 3D-bioprinted hydrogel. Embryo quality was evaluated based on cleavage speed and blastocyst ratio on the GelMA hydrogel. Whole-transcriptome next-generation sequencing (NGS) analysis of embryos was used to identify biomechanical signaling factors. Our findings revealed that 10 kPa GelMA hydrogel culture conditions performed better with respect to development speed, blastocyst ratio, and hatching ratio than the control condition. Whole transcriptome NGS revealed up-regulation of mRNA processing genes and protein transport genes by the 7 and 10 kPa hydrogels. Furthermore, the inner cell mass and the number of Oct4+ cells were significantly higher in blastocysts cultured on 10 kPa hydrogel dishes than in those cultured on conventional hard plastic dishes. These findings demonstrate that optimized oviduct-mimic hydrogel-based 3D GelMA culture dishes could improve in vitro embryo development. Hence, 3D GelMA culture dishes may be useful as human embryo culture systems for assisted reproductive techniques.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141814445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Titanium alloy, particularly Ti6Al4V, is commonly used for constructing the framework of implant-supported fixed complete dentures (IFCDs) but exhibits poor specific strength and impact toughness. Three-periodic minimal surface (TPMS) porous structures have the advantages of high specific strength, lightweight, and shock and energy absorption. Therefore, the functionally graded TPMS porous structure was adopted to design the framework for IFCDs in this study. Nine types of TPMS-based lattice structures with radial gradient variations were designed. Finite element analysis and experimental results indicate that the relative density increases outward and the cell size decreases outward from the center. The B-I porous structure has the highest strength and impact toughness compared to other gradient porous structure types. Moreover, the IFCD framework, utilizing the B-I porous structure, exhibited a 50% reduction in weight compared to the solid framework. When compared to the hollow framework with the same weight, the B-I framework demonstrated a 42.81% lower maximum equivalent stress under normal chewing conditions without undergoing plastic deformation. Therefore, the B-I framework meets the mechanical performance requirements for daily chewing and exhibits superior mechanical properties over conventional structures.
{"title":" A functionally graded gyroid-type three-periodic minimal surface framework applied to implant-supported fixed complete dentures","authors":"Jiwei Ren, Renkai Huang, linqin Huang, Shaoying Yang, Chunrong Pan, Yuchun Sun, Sukun Tian, Xuehua Wu, Dongsheng Wang, Youwen Yang","doi":"10.36922/ijb.3453","DOIUrl":"https://doi.org/10.36922/ijb.3453","url":null,"abstract":"Titanium alloy, particularly Ti6Al4V, is commonly used for constructing the framework of implant-supported fixed complete dentures (IFCDs) but exhibits poor specific strength and impact toughness. Three-periodic minimal surface (TPMS) porous structures have the advantages of high specific strength, lightweight, and shock and energy absorption. Therefore, the functionally graded TPMS porous structure was adopted to design the framework for IFCDs in this study. Nine types of TPMS-based lattice structures with radial gradient variations were designed. Finite element analysis and experimental results indicate that the relative density increases outward and the cell size decreases outward from the center. The B-I porous structure has the highest strength and impact toughness compared to other gradient porous structure types. Moreover, the IFCD framework, utilizing the B-I porous structure, exhibited a 50% reduction in weight compared to the solid framework. When compared to the hollow framework with the same weight, the B-I framework demonstrated a 42.81% lower maximum equivalent stress under normal chewing conditions without undergoing plastic deformation. Therefore, the B-I framework meets the mechanical performance requirements for daily chewing and exhibits superior mechanical properties over conventional structures.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Walaa F. Alsanie, Sherin Abdelrahman, M. Alhomrani, Alexander U. Valle-Pérez, Ebtisam Abdulah Alosimi, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Abdulhakeem S. Alamri, Abdulaziz Alsharif, Bassem M. Raafat, Yusuf S. Althobaiti, Ahmed Gaber, Charlotte A. E. Hauser
Pregabalin is a widely prescribed drug for various neurological disorders, yet its effects on embryonic cortical neuron development when given to pregnant women remain inadequately explored. In this study, we employed advanced three-dimensional (3D) culturing and in-house developed high-throughput robotic 3D bioprinting technologies to evaluate their potential in neuropharmacology applications, using pregabalin as a model compound. Using a robotic 3D bioprinter and tetrameric IIZK peptide hydrogel as bioink, we created constructs with pregabalin-treated and untreated primary mouse embryonic cortical neurons. This setup allowed us to study the drug’s effects on cell viability, expression of neuronal markers, and neuron development. Our comparative analysis between 2D and 3D peptide-based cell culture models revealed that at a therapeutic concentration of 10 μM, pregabalin does not affect neuronal viability or the morphogenesis of cortical neurons. However, it significantly alters adenosine triphosphate (ATP) release, suggesting potential disruptions in mitochondrial function. Moreover, gene expression analysis of key genes involved in the development of the forebrain and the differentiation and maturation of neurons revealed significant alterations, including the downregulation of Dlx2, Nhlh2, Otp, and Gad67. These findings, together with observed alterations in neuronal activity and oscillations, emphasize the complex impact of pregabalin on neuronal development and function. They highlight the necessity for comprehensive clinical evaluations of its use during pregnancy. Furthermore, our research demonstrates the feasibility and value of integrating 3D cultures with high-throughput 3D bioprinting in neuropharmacology, opening new avenues for investigating drug effects on neuronal development and function, and contributing to safer clinical practices.
{"title":"Investigating the effect of pregabalin on neuronal development using ultrashort self-assembling peptides: Assessing 3D neuronal cultures with high throughput robotic 3D bioprinting","authors":"Walaa F. Alsanie, Sherin Abdelrahman, M. Alhomrani, Alexander U. Valle-Pérez, Ebtisam Abdulah Alosimi, Hamza Habeeballah, Heba A. Alkhatabi, Raed I. Felimban, Abdulhakeem S. Alamri, Abdulaziz Alsharif, Bassem M. Raafat, Yusuf S. Althobaiti, Ahmed Gaber, Charlotte A. E. Hauser","doi":"10.36922/ijb.3010","DOIUrl":"https://doi.org/10.36922/ijb.3010","url":null,"abstract":"Pregabalin is a widely prescribed drug for various neurological disorders, yet its effects on embryonic cortical neuron development when given to pregnant women remain inadequately explored. In this study, we employed advanced three-dimensional (3D) culturing and in-house developed high-throughput robotic 3D bioprinting technologies to evaluate their potential in neuropharmacology applications, using pregabalin as a model compound. Using a robotic 3D bioprinter and tetrameric IIZK peptide hydrogel as bioink, we created constructs with pregabalin-treated and untreated primary mouse embryonic cortical neurons. This setup allowed us to study the drug’s effects on cell viability, expression of neuronal markers, and neuron development. Our comparative analysis between 2D and 3D peptide-based cell culture models revealed that at a therapeutic concentration of 10 μM, pregabalin does not affect neuronal viability or the morphogenesis of cortical neurons. However, it significantly alters adenosine triphosphate (ATP) release, suggesting potential disruptions in mitochondrial function. Moreover, gene expression analysis of key genes involved in the development of the forebrain and the differentiation and maturation of neurons revealed significant alterations, including the downregulation of Dlx2, Nhlh2, Otp, and Gad67. These findings, together with observed alterations in neuronal activity and oscillations, emphasize the complex impact of pregabalin on neuronal development and function. They highlight the necessity for comprehensive clinical evaluations of its use during pregnancy. Furthermore, our research demonstrates the feasibility and value of integrating 3D cultures with high-throughput 3D bioprinting in neuropharmacology, opening new avenues for investigating drug effects on neuronal development and function, and contributing to safer clinical practices.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141824829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shangsi Chen, Yue Wang, Junzhi Li, Haoran Sun, Ming-Fung Francis Siu, Shenglong Tan
The development of bifunctional scaffolds for clinical applications, aimed at preventing tumor recurrence and promoting bone tissue regeneration simultaneously at the surgical site, is imperative in repairing bone tumor-related defects. In the current study, Mg-substituted hydroxyapatite (MgHAp) nanocomposites were synthesized via a biomineralization process. Doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in polydopamine (PDA) particles to synthesize PDA@DOX particles. MgHAp/gelatin methacryloyl (GelMA) hydrogels encapsulated with PDA@DOX particles were designed and fabricated to construct MgHAp/GelMA-PDA@DOX hydrogels via 3D printing. The 3D-printed MgHAp/GelMA-PDA@DOX hydrogels exhibited antitumor synergy by providing combined chemotherapy and phototherapy for bone tumor cell ablation. The hydrogels showed a good photothermal effect and could induce hyperthermia upon irradiation with an 808 nm near-infrared (NIR) laser. Moreover, MgHAp/GelMA-PDA@DOX hydrogels could release DOX sustainably and controllably. In vitro experiments demonstrated that 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could effectively eradicate MG63 cells through the synergy of induced hyperthermia and DOX release. Furthermore, due to the sustained release of Mg2+, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could promote the proliferation of rat bone marrow-derived mesenchymal stem cells and facilitate alkaline phosphatase activity and the expression of osteogenic genes, such as osteocalcin (Ocn), type I collagen (Col1), runt-related transcription factor-2 (Runx2), and bone morphogenetic protein-2 (Bmp2), indicating their excellent osteogenic effect. As a result, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels showed great potential in the treatment of bone tumor-related defects by effectively killing tumor cells and simultaneously promoting bone tissue regeneration.
{"title":"3D-printed Mg-substituted hydroxyapatite/ gelatin methacryloyl hydrogels encapsulated with PDA@DOX particles for bone tumor therapy and bone tissue regeneration","authors":"Shangsi Chen, Yue Wang, Junzhi Li, Haoran Sun, Ming-Fung Francis Siu, Shenglong Tan","doi":"10.36922/ijb.3526","DOIUrl":"https://doi.org/10.36922/ijb.3526","url":null,"abstract":"The development of bifunctional scaffolds for clinical applications, aimed at preventing tumor recurrence and promoting bone tissue regeneration simultaneously at the surgical site, is imperative in repairing bone tumor-related defects. In the current study, Mg-substituted hydroxyapatite (MgHAp) nanocomposites were synthesized via a biomineralization process. Doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in polydopamine (PDA) particles to synthesize PDA@DOX particles. MgHAp/gelatin methacryloyl (GelMA) hydrogels encapsulated with PDA@DOX particles were designed and fabricated to construct MgHAp/GelMA-PDA@DOX hydrogels via 3D printing. The 3D-printed MgHAp/GelMA-PDA@DOX hydrogels exhibited antitumor synergy by providing combined chemotherapy and phototherapy for bone tumor cell ablation. The hydrogels showed a good photothermal effect and could induce hyperthermia upon irradiation with an 808 nm near-infrared (NIR) laser. Moreover, MgHAp/GelMA-PDA@DOX hydrogels could release DOX sustainably and controllably. In vitro experiments demonstrated that 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could effectively eradicate MG63 cells through the synergy of induced hyperthermia and DOX release. Furthermore, due to the sustained release of Mg2+, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could promote the proliferation of rat bone marrow-derived mesenchymal stem cells and facilitate alkaline phosphatase activity and the expression of osteogenic genes, such as osteocalcin (Ocn), type I collagen (Col1), runt-related transcription factor-2 (Runx2), and bone morphogenetic protein-2 (Bmp2), indicating their excellent osteogenic effect. As a result, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels showed great potential in the treatment of bone tumor-related defects by effectively killing tumor cells and simultaneously promoting bone tissue regeneration.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141828049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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