Bin Huang, Zengjie Zhao, Yayu Zheng, Kaidi Xu, Dan Wang, Qingyuan Yang, Tingting Yang, Xiaojie Yang, H. Chen
The integration of conductive hydrogels and advanced three-dimensional (3D) printing is a trigger of the development of biomedical sensors for healthcare diagnostics and personalized treatment. Poly(3,4-ethylenedioxythiophene):poly(styr ene sulfonate) (PEDOT:PSS) is a versatile conductive hydrogel materials renowned for its exceptional conductivity and hydrophilicity, and 3D printing technology allows for precise and customized fabrication of electronic components and devices. In this review, we aim to explore the potential of 3D-printed PEDOT/PSS conductive hydrogel in the fabrication of biomedical sensors, with a focus on their distinct characteristics, application potential, and systematic classification. We also discuss the methods for fabricating PEDOT:PSS hydrogel electronic devices by employing 3D printing techniques, including extrusion-based 3D printing technology (fused deposition modeling, direct ink writing, and inkjet printing), powder-based 3D printing technology (selective laser sintering and selective laser melting), and photopolymerization-based 3D printing technology (stereolithography and digital light processing). The applications of 2D/3D-printed PEDOT:PSS hydrogels in biomedical sensors, such as strain sensors, pressure sensors, stretchable sensors, electrochemical sensors, temperature sensors, humidity sensors, and electrocardiogram sensor, are also summarized in this review. Finally, we provide insights into the development of 3D-printed PEDOT:PSS-based biomedical sensors and the innovative techniques for biomedical sensor integration.
{"title":"2D/3D-printed PEDOT/PSS conductive hydrogel for biomedical sensors","authors":"Bin Huang, Zengjie Zhao, Yayu Zheng, Kaidi Xu, Dan Wang, Qingyuan Yang, Tingting Yang, Xiaojie Yang, H. Chen","doi":"10.36922/ijb.1725","DOIUrl":"https://doi.org/10.36922/ijb.1725","url":null,"abstract":"The integration of conductive hydrogels and advanced three-dimensional (3D) printing is a trigger of the development of biomedical sensors for healthcare diagnostics and personalized treatment. Poly(3,4-ethylenedioxythiophene):poly(styr ene sulfonate) (PEDOT:PSS) is a versatile conductive hydrogel materials renowned for its exceptional conductivity and hydrophilicity, and 3D printing technology allows for precise and customized fabrication of electronic components and devices. In this review, we aim to explore the potential of 3D-printed PEDOT/PSS conductive hydrogel in the fabrication of biomedical sensors, with a focus on their distinct characteristics, application potential, and systematic classification. We also discuss the methods for fabricating PEDOT:PSS hydrogel electronic devices by employing 3D printing techniques, including extrusion-based 3D printing technology (fused deposition modeling, direct ink writing, and inkjet printing), powder-based 3D printing technology (selective laser sintering and selective laser melting), and photopolymerization-based 3D printing technology (stereolithography and digital light processing). The applications of 2D/3D-printed PEDOT:PSS hydrogels in biomedical sensors, such as strain sensors, pressure sensors, stretchable sensors, electrochemical sensors, temperature sensors, humidity sensors, and electrocardiogram sensor, are also summarized in this review. Finally, we provide insights into the development of 3D-printed PEDOT:PSS-based biomedical sensors and the innovative techniques for biomedical sensor integration.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139619783","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}
Dahong Kim, Su Jeong Lee, Dongjin Lee, Ji Min Seok, Seon Ju Yeo, Hyungjun Lim, Jae Jong Lee, Jae Hwang Song, Kangwon Lee, Won Ho Park, Su A Park
Polyhydroxyalkanoates (PHAs) have gained much attention as a potential alternative to conventional plastic bone scaffolds due to their biocompatibility and biodegradability, among a diverse range of advantageous properties. However, the water resistance of PHA creates an environment that can interfere with cell interactions. In this study, a three-dimensional-printed PHA scaffold was fabricated through fused deposition modeling printing considering the physical properties of PHA. The PHA bone scaffolds were then coated with polydopamine (pDA) and/or hydroxyapatite (HA) in various configurations using a relatively simple and rapid process involving only immersion. The PHA–pDA– HA scaffold showed enhanced cell viability, proliferation, and differentiation, and could thus serve as a versatile platform for bone tissue engineering applications.
聚羟基烷酸酯（PHA）具有生物相容性和生物可降解性等多种优势，是传统塑料骨支架的潜在替代品，因此备受关注。然而，PHA 的耐水性会造成干扰细胞相互作用的环境。在本研究中，考虑到 PHA 的物理特性，通过熔融沉积建模打印技术制作了三维打印 PHA 支架。然后，采用相对简单、快速的浸泡工艺，在 PHA 骨支架上涂覆各种配置的聚多巴胺（pDA）和/或羟基磷灰石（HA）。PHA-pDA- HA 支架显示出更强的细胞活力、增殖和分化能力，因此可作为骨组织工程应用的多功能平台。
{"title":"Biomimetic mineralization of 3D-printed polyhydroxyalkanoate-based microbial scaffolds for bone tissue engineering","authors":"Dahong Kim, Su Jeong Lee, Dongjin Lee, Ji Min Seok, Seon Ju Yeo, Hyungjun Lim, Jae Jong Lee, Jae Hwang Song, Kangwon Lee, Won Ho Park, Su A Park","doi":"10.36922/ijb.1806","DOIUrl":"https://doi.org/10.36922/ijb.1806","url":null,"abstract":"Polyhydroxyalkanoates (PHAs) have gained much attention as a potential alternative to conventional plastic bone scaffolds due to their biocompatibility and biodegradability, among a diverse range of advantageous properties. However, the water resistance of PHA creates an environment that can interfere with cell interactions. In this study, a three-dimensional-printed PHA scaffold was fabricated through fused deposition modeling printing considering the physical properties of PHA. The PHA bone scaffolds were then coated with polydopamine (pDA) and/or hydroxyapatite (HA) in various configurations using a relatively simple and rapid process involving only immersion. The PHA–pDA– HA scaffold showed enhanced cell viability, proliferation, and differentiation, and could thus serve as a versatile platform for bone tissue engineering applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139620506","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}
Mengmeng Li, Yan Wu, Miaomiao Wang, Wencai Zhang, Peiran Song, Jiacan Su
Degenerative osteoarthritis, a common sequela of articular cartilage defect, significantly impacts the quality of life of millions of individuals worldwide. Three-dimensional (3D) bioprinting has emerged as an advanced tissue engineering strategy, offering precise spatial arrangements of cells, hydrogels, and bioactive cues. Hyaluronic acid (HA) is a crucial component of bioink designed for fabricating cartilage tissue. However, creating a bioink that closely mimics the cartilaginous extracellular matrix (ECM) still remains a challenge. HA hydrogels have limitations in recapitulating tunable mechanical properties, stimuli responsiveness, and flexibility in ligands’ adhesion akin to those of native tissues. In recent years, DNA has emerged as a smart biomaterial that endows hydrogels with tunable properties and allows for precise structural customization of the hydrogels due to its unique programmability. Integrating reversible DNA linkages, reconfigurable DNA architectures, DNA plasmid, and targeted DNA aptamers into HA hydrogels allows them to respond to the extracellular environment and express desired molecules, making them ideal artificial ECMs for 3D bioprinting of cartilage tissue. This review targets this challenge by highlighting the characteristics of DNA moieties designed as reversible crosslinkers, responsive units, and adhesion ligands to functionalize HA hydrogels. Furthermore, we offer perspectives on how DNA-functionalized HA hydrogels can be harnessed to create dynamic and biomimetic bioink capable of recapitulating the more complex functions required for cartilage tissue engineering.
退行性骨关节炎是关节软骨缺损的常见后遗症，严重影响着全球数百万人的生活质量。三维（3D）生物打印已成为一种先进的组织工程策略，可提供细胞、水凝胶和生物活性线索的精确空间排列。透明质酸（HA）是用于制造软骨组织的生物墨水的重要成分。然而，要制造出一种能紧密模拟软骨细胞外基质（ECM）的生物墨水仍然是一项挑战。HA 水凝胶在再现可调机械特性、刺激响应性和配体粘附灵活性方面存在局限性，无法与原生组织相媲美。近年来，DNA 已成为一种智能生物材料，它赋予了水凝胶可调的特性，并因其独特的可编程性而实现了水凝胶结构的精确定制。将可逆 DNA 连接、可重构 DNA 架构、DNA 质粒和靶向 DNA 合体整合到 HA 水凝胶中，可使它们对细胞外环境做出反应并表达所需的分子，从而使它们成为软骨组织三维生物打印的理想人工 ECM。本综述针对这一挑战，重点介绍了 DNA 分子作为可逆交联剂、反应单元和粘附配体的特点，以对 HA 水凝胶进行功能化。此外，我们还对如何利用 DNA 功能化 HA 水凝胶来创建动态仿生生物墨水提出了展望，这种生物墨水能够重现软骨组织工程所需的更复杂功能。
{"title":"DNA-functionalized hyaluronic acid bioink in cartilage engineering: a perspective","authors":"Mengmeng Li, Yan Wu, Miaomiao Wang, Wencai Zhang, Peiran Song, Jiacan Su","doi":"10.36922/ijb.1814","DOIUrl":"https://doi.org/10.36922/ijb.1814","url":null,"abstract":"Degenerative osteoarthritis, a common sequela of articular cartilage defect, significantly impacts the quality of life of millions of individuals worldwide. Three-dimensional (3D) bioprinting has emerged as an advanced tissue engineering strategy, offering precise spatial arrangements of cells, hydrogels, and bioactive cues. Hyaluronic acid (HA) is a crucial component of bioink designed for fabricating cartilage tissue. However, creating a bioink that closely mimics the cartilaginous extracellular matrix (ECM) still remains a challenge. HA hydrogels have limitations in recapitulating tunable mechanical properties, stimuli responsiveness, and flexibility in ligands’ adhesion akin to those of native tissues. In recent years, DNA has emerged as a smart biomaterial that endows hydrogels with tunable properties and allows for precise structural customization of the hydrogels due to its unique programmability. Integrating reversible DNA linkages, reconfigurable DNA architectures, DNA plasmid, and targeted DNA aptamers into HA hydrogels allows them to respond to the extracellular environment and express desired molecules, making them ideal artificial ECMs for 3D bioprinting of cartilage tissue. This review targets this challenge by highlighting the characteristics of DNA moieties designed as reversible crosslinkers, responsive units, and adhesion ligands to functionalize HA hydrogels. Furthermore, we offer perspectives on how DNA-functionalized HA hydrogels can be harnessed to create dynamic and biomimetic bioink capable of recapitulating the more complex functions required for cartilage tissue engineering.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139619688","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}
Yinchu Dong, Wenbi Wu, Haofan Liu, Xuebing Jiang, Li Li, Li Zhang, Yi Zhang, Jing Luo, Maling Gou
Branched nerve guidance conduit (NGC) provides a promising alternative to autografts for the effective treatment of severe peripheral nerve injuries. Despite this, the impact of branched architecture on nerve regeneration remains unclear, particularly concerning branch angle and number in multi-branched NGCs. In this study, we investigated the effects of branch angle and number on nerve regeneration by preparing and characterizing multi-angled and multi-branched NGCs. We designed and fabricated dual-branched NGCs (DBNs) with various branch angles and multi-branched NGCs (MBNs) through a digital light processing (DLP) printing process. When branched NGCs were implanted to bridge the linear sciatic nerve gap, nerve dual branches with acute (45°), right (90°), or obtuse (120°) branch angles were formed in DBNs, while nerve multi-branches were generated in MBNs. The regenerated nerves in DBNs with various angles exhibited comparable electrophysiological conduction and histological morphologies, indicating that the branch angle of dual-branched NGCs may not affect nerve branch regeneration. In contrast, the diameter of the regenerated nerve branches in MBNs decreased with increasing distance from the scaffold center, highlighting the potential significance of branch number in the design of branched NGCs. This study contributes valuable insights for designing, preparing, and applying branched NGCs, offering potential assistance in advancing nerve regeneration strategies.
分枝神经引导导管（NGC）为有效治疗严重的周围神经损伤提供了一种替代自体移植物的可行方法。尽管如此，分支结构对神经再生的影响仍不清楚，尤其是多分支 NGC 的分支角度和数量。在本研究中，我们通过制备多角度和多分支 NGC 并对其进行表征，研究了分支角度和数量对神经再生的影响。我们设计并通过数字光处理（DLP）打印工艺制备了具有不同分支角度的双分支 NGC（DBN）和多分支 NGC（MBN）。当植入分枝NGCs以弥合线性坐骨神经间隙时，在DBNs中形成了锐角（45°）、直角（90°）或钝角（120°）的神经双分支，而在MBNs中则产生了神经多分支。在不同角度的 DBN 中再生的神经表现出相似的电生理传导和组织学形态，这表明双分支 NGC 的分支角度可能不会影响神经分支的再生。相反，MBNs 中再生神经分支的直径随着与支架中心距离的增加而减小，这凸显了分支数量在设计分枝 NGCs 中的潜在意义。这项研究为设计、制备和应用支化 NGCs 提供了宝贵的见解，为推进神经再生策略提供了潜在的帮助。
{"title":"Preparation and characterization of angled dual- and multi-branched nerve guidance conduits","authors":"Yinchu Dong, Wenbi Wu, Haofan Liu, Xuebing Jiang, Li Li, Li Zhang, Yi Zhang, Jing Luo, Maling Gou","doi":"10.36922/ijb.1750","DOIUrl":"https://doi.org/10.36922/ijb.1750","url":null,"abstract":"Branched nerve guidance conduit (NGC) provides a promising alternative to autografts for the effective treatment of severe peripheral nerve injuries. Despite this, the impact of branched architecture on nerve regeneration remains unclear, particularly concerning branch angle and number in multi-branched NGCs. In this study, we investigated the effects of branch angle and number on nerve regeneration by preparing and characterizing multi-angled and multi-branched NGCs. We designed and fabricated dual-branched NGCs (DBNs) with various branch angles and multi-branched NGCs (MBNs) through a digital light processing (DLP) printing process. When branched NGCs were implanted to bridge the linear sciatic nerve gap, nerve dual branches with acute (45°), right (90°), or obtuse (120°) branch angles were formed in DBNs, while nerve multi-branches were generated in MBNs. The regenerated nerves in DBNs with various angles exhibited comparable electrophysiological conduction and histological morphologies, indicating that the branch angle of dual-branched NGCs may not affect nerve branch regeneration. In contrast, the diameter of the regenerated nerve branches in MBNs decreased with increasing distance from the scaffold center, highlighting the potential significance of branch number in the design of branched NGCs. This study contributes valuable insights for designing, preparing, and applying branched NGCs, offering potential assistance in advancing nerve regeneration strategies.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139530021","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}
Jaewoo Choi, Eun Ji Lee, Hye ji Lim, Dong Myoung Lee, Deokhyeon Yoon, Gi Hoon Yang, Eunjeong Choi, Hojun Jeon, K. Lee, Yong-Il Shin, Sang-Cheol Han, W. Jang, Sang-Mo Kwon
Vascular diseases, including ischemic conditions and restenosis, pose significant challenges in clinical practice. Restenosis, the re-narrowing of blood vessels after interventions such as stent placement, remains a major concern despite advances in medical interventions. Addressing these challenges requires innovative approaches that promote vascular regeneration and prevent restenosis. By leveraging the capabilities of three-dimensional (3D) printing technology, artificial blood vessels with lumen can be precisely constructed in customizable sizes, closely mimicking the natural vascular architecture. This approach allows for the incorporation of therapeutic agents and cells to enhance the functionality of the fabricated vessels. In the present study, we investigated the fabrication and characterization of artificial blood vessels using 3D printing technology, with the focus on achieving precise control over the vessel dimensions and architecture to ensure optimal functionality. The use of 3D printing enabled the creation of patient-specific blood vessels with tailored sizes and geometries, providing a personalized solution for vascular treatment. Furthermore, we explored the integration of nanoparticles loaded with therapeutic drugs within the 3D-printed blood vessels. Specifically, rapamycin, a potent drug for preventing restenosis, was encapsulated within the nanoparticles to enable controlled drug release. This approach aimed to address the challenge of restenosis by delivering the drug directly to the affected site and maintaining its therapeutic concentration over an extended period. Additionally, the study investigated the incorporation of endothelial progenitor cells (EPCs), which promote re-endothelialization essential for vascular regeneration and long-term vessel functionality, within the artificial blood vessels. The 3D-printed blood vessels provide an ideal environment for the integration and growth of these cells, further enhancing their regenerative potential. By combining 3D printing technology, drug-loaded nanoparticles, and EPCs, this study demonstrated the potential of this approach in fabricating functional artificial blood vessels.
血管疾病，包括缺血性疾病和血管再狭窄，给临床实践带来了巨大挑战。血管再狭窄是指血管在接受支架置入等介入治疗后重新变窄，尽管医疗介入技术不断进步，但这仍然是一个令人担忧的主要问题。要应对这些挑战，就必须采取创新方法，促进血管再生，防止再狭窄。利用三维（3D）打印技术的能力，可以精确地构建出具有管腔的人造血管，其尺寸可定制，与天然血管结构非常相似。通过这种方法可以加入治疗剂和细胞，增强人造血管的功能。在本研究中，我们利用三维打印技术研究了人造血管的制造和表征，重点是实现对血管尺寸和结构的精确控制，以确保最佳功能。通过使用三维打印技术，我们创建了具有定制尺寸和几何形状的患者专用血管，为血管治疗提供了个性化解决方案。此外，我们还探索了在 3D 打印血管中整合装载治疗药物的纳米颗粒。具体来说，雷帕霉素是一种预防血管再狭窄的强效药物，我们将其封装在纳米颗粒中，以实现药物的可控释放。这种方法旨在将药物直接输送到受影响的部位，并在较长的时间内保持其治疗浓度，从而解决血管再狭窄的难题。此外，该研究还探讨了在人造血管中加入内皮祖细胞（EPCs）的问题，EPCs 可促进血管再生和血管长期功能所必需的再内皮化。三维打印血管为这些细胞的整合和生长提供了理想的环境，进一步增强了它们的再生潜力。通过将三维打印技术、药物纳米颗粒和 EPCs 结合起来，这项研究证明了这种方法在制造功能性人造血管方面的潜力。
{"title":"Development of 3D-bioprinted artificial blood vessels loaded with rapamycin-nanoparticles for ischemic repair","authors":"Jaewoo Choi, Eun Ji Lee, Hye ji Lim, Dong Myoung Lee, Deokhyeon Yoon, Gi Hoon Yang, Eunjeong Choi, Hojun Jeon, K. Lee, Yong-Il Shin, Sang-Cheol Han, W. Jang, Sang-Mo Kwon","doi":"10.36922/ijb.1465","DOIUrl":"https://doi.org/10.36922/ijb.1465","url":null,"abstract":"Vascular diseases, including ischemic conditions and restenosis, pose significant challenges in clinical practice. Restenosis, the re-narrowing of blood vessels after interventions such as stent placement, remains a major concern despite advances in medical interventions. Addressing these challenges requires innovative approaches that promote vascular regeneration and prevent restenosis. By leveraging the capabilities of three-dimensional (3D) printing technology, artificial blood vessels with lumen can be precisely constructed in customizable sizes, closely mimicking the natural vascular architecture. This approach allows for the incorporation of therapeutic agents and cells to enhance the functionality of the fabricated vessels. In the present study, we investigated the fabrication and characterization of artificial blood vessels using 3D printing technology, with the focus on achieving precise control over the vessel dimensions and architecture to ensure optimal functionality. The use of 3D printing enabled the creation of patient-specific blood vessels with tailored sizes and geometries, providing a personalized solution for vascular treatment. Furthermore, we explored the integration of nanoparticles loaded with therapeutic drugs within the 3D-printed blood vessels. Specifically, rapamycin, a potent drug for preventing restenosis, was encapsulated within the nanoparticles to enable controlled drug release. This approach aimed to address the challenge of restenosis by delivering the drug directly to the affected site and maintaining its therapeutic concentration over an extended period. Additionally, the study investigated the incorporation of endothelial progenitor cells (EPCs), which promote re-endothelialization essential for vascular regeneration and long-term vessel functionality, within the artificial blood vessels. The 3D-printed blood vessels provide an ideal environment for the integration and growth of these cells, further enhancing their regenerative potential. By combining 3D printing technology, drug-loaded nanoparticles, and EPCs, this study demonstrated the potential of this approach in fabricating functional artificial blood vessels.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139620581","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}
Poly (lactic acid)/poly (glycolic acid) (LG) bone scaffold exhibits good biocompatibility for bone defect regeneration but lacks satisfactory mechanical and osteogenic induction properties. Here, graphene oxide (GO) was encapsulated by polydopamine (PDA) via self-polymerization of dopamine, and strontium (Sr) was loaded onto GO by the chelation of PDA. The modified GO was added to the LG scaffold prepared via selective laser sintering as a reinforcing phase to improve the mechanical properties and osteogenic induction properties. The results indicated that the tensile and compressive strengths of the scaffold with 1.5 wt% modified GO were 9.49 MPa and 19.22 MPa, respectively, representing 67.08% and 95.33% improvement compared to the LG scaffold. The enhancement mechanisms of the modified GO in the scaffold included crack branching, crack deflection, crack pinning, crack bridging, and pulling out. More importantly, the scaffold with modified GO exhibited superior bioactivity and osteogenic induction properties compared to the LG scaffold, because PDA could chelate calcium ions derived from the surrounding physiological environment, and the calcium ions attracted phosphate ions through electrostatic interactions to promote the apatite layer deposition. Additionally, the presence of Sr in the scaffold promoted the proliferation and differentiation of osteoblasts, thereby improving osteogenic induction properties.
聚（乳酸）/聚（乙醇酸）（LG）骨支架在骨缺损再生方面具有良好的生物相容性，但缺乏令人满意的机械和成骨诱导特性。在这里，氧化石墨烯（GO）通过多巴胺的自聚合作用被聚多巴胺（PDA）包裹，锶（Sr）通过 PDA 的螯合作用被负载到 GO 上。通过选择性激光烧结技术制备的 LG 支架中添加了改性 GO 作为增强相，以改善其力学性能和成骨诱导性能。结果表明，含有 1.5 wt% 改性 GO 的支架的拉伸强度和压缩强度分别为 9.49 MPa 和 19.22 MPa，与 LG 支架相比分别提高了 67.08% 和 95.33%。支架中改性 GO 的增强机制包括裂纹分支、裂纹偏转、裂纹针刺、裂纹桥接和拔出。更重要的是，与 LG 支架相比，改性 GO 支架表现出更优越的生物活性和成骨诱导特性，这是因为 PDA 可以螯合周围生理环境中的钙离子，钙离子通过静电作用吸引磷酸盐离子，促进磷灰石层沉积。此外，支架中 Sr 的存在促进了成骨细胞的增殖和分化，从而改善了成骨诱导特性。
{"title":"Polydopamine chelating strontium on graphene oxide enhances the mechanical and osteogenic induction properties of PLLA/PGA bone scaffold ","authors":"Feng Yang, Yun Lin, Saipu Shen, Yulong Gu, C. Shuai, Pei Feng","doi":"10.36922/ijb.1829","DOIUrl":"https://doi.org/10.36922/ijb.1829","url":null,"abstract":"Poly (lactic acid)/poly (glycolic acid) (LG) bone scaffold exhibits good biocompatibility for bone defect regeneration but lacks satisfactory mechanical and osteogenic induction properties. Here, graphene oxide (GO) was encapsulated by polydopamine (PDA) via self-polymerization of dopamine, and strontium (Sr) was loaded onto GO by the chelation of PDA. The modified GO was added to the LG scaffold prepared via selective laser sintering as a reinforcing phase to improve the mechanical properties and osteogenic induction properties. The results indicated that the tensile and compressive strengths of the scaffold with 1.5 wt% modified GO were 9.49 MPa and 19.22 MPa, respectively, representing 67.08% and 95.33% improvement compared to the LG scaffold. The enhancement mechanisms of the modified GO in the scaffold included crack branching, crack deflection, crack pinning, crack bridging, and pulling out. More importantly, the scaffold with modified GO exhibited superior bioactivity and osteogenic induction properties compared to the LG scaffold, because PDA could chelate calcium ions derived from the surrounding physiological environment, and the calcium ions attracted phosphate ions through electrostatic interactions to promote the apatite layer deposition. Additionally, the presence of Sr in the scaffold promoted the proliferation and differentiation of osteoblasts, thereby improving osteogenic induction properties.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139624258","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}
More than 90% of kidney cancers are attributed to renal cell carcinoma (RCC), which is however highly resistant to traditional chemotherapy. The challenges met in treating RCC signify an imperative to accelerate the development of new and effective drugs. Preclinical testing has served as a foundation for evaluating potential effectiveness of new drugs, but this endeavor is deeply restricted by the current generation of in vitro two-dimensional culture models, which cannot accurately mimic the tumor microenvironment (TME). Therefore, new in vitro three-dimensional (3D) cell culture models that can better mimic the components and architecture of TME have been developed for preclinical testing, but only a few existing 3D cell culture models can simulate the TME of RCC, representing a limitative obstacle impeding the development of novel drugs for RCC. In this study, we prepared a bioink by mixing porcine kidney decellularized extracellular matrix (dECM) powders with gelatin methacryloyl (GelMA) to bioprint an in vitro 3D cell culture model for RCC. We found that GelMA stability, mechanical properties, and printability were all significantly improved following the addition of the dECM powder. Moreover, cell cultures using ACHN cells suggested that kidney dECM powders significantly improved the cellular proliferation and metastasis via upregulation of markers related to epithelial– mesenchymal transition, along with activation of several cancer progression-related signaling pathways. More importantly, ACHN cells also demonstrated higher resistance to sunitinib under the stimulation of kidney dECM, indicating that GelMA-kidney dECM hydrogels may be an appropriate preclinical model to be used for building an in vitro RCC platform for drug screening and development.
{"title":"Decellularized porcine kidney-incorporated hydrogels for cell-laden bioprinting of renal cell carcinoma model","authors":"Miaoben Wu, Hangyu Zhou, Jingying Hu, Zonghuan Wang, Yongqi Xu, Yibing Wu, Yang Xiang, Jun Yin, Peng Wei, Kailei Xu, Tiantian Ren","doi":"10.36922/ijb.1413","DOIUrl":"https://doi.org/10.36922/ijb.1413","url":null,"abstract":"More than 90% of kidney cancers are attributed to renal cell carcinoma (RCC), which is however highly resistant to traditional chemotherapy. The challenges met in treating RCC signify an imperative to accelerate the development of new and effective drugs. Preclinical testing has served as a foundation for evaluating potential effectiveness of new drugs, but this endeavor is deeply restricted by the current generation of in vitro two-dimensional culture models, which cannot accurately mimic the tumor microenvironment (TME). Therefore, new in vitro three-dimensional (3D) cell culture models that can better mimic the components and architecture of TME have been developed for preclinical testing, but only a few existing 3D cell culture models can simulate the TME of RCC, representing a limitative obstacle impeding the development of novel drugs for RCC. In this study, we prepared a bioink by mixing porcine kidney decellularized extracellular matrix (dECM) powders with gelatin methacryloyl (GelMA) to bioprint an in vitro 3D cell culture model for RCC. We found that GelMA stability, mechanical properties, and printability were all significantly improved following the addition of the dECM powder. Moreover, cell cultures using ACHN cells suggested that kidney dECM powders significantly improved the cellular proliferation and metastasis via upregulation of markers related to epithelial– mesenchymal transition, along with activation of several cancer progression-related signaling pathways. More importantly, ACHN cells also demonstrated higher resistance to sunitinib under the stimulation of kidney dECM, indicating that GelMA-kidney dECM hydrogels may be an appropriate preclinical model to be used for building an in vitro RCC platform for drug screening and development.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139531610","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}
Eun Ji Lee, Jaewoo Choi, Hye ji Lim, Deokhyeon Yoon, Dong Myoung Lee, Donggu Kang, Jeong-Seok Lee, Hojun Jeon, Kyeong Hyeon Lee, Yong-Il Shin, Sang-Cheol Han, W. Jang, Sang-Mo Kwon
Vascular regeneration plays a critical role in the treatment of cardiovascular diseases and in tissue engineering applications. In this study, we fabricated and characterized statin/curcumin-loaded nanoparticles for potential applications in vascular regeneration. The nanoparticles exhibited consistent spherical shape and sizes, indicating reproducibility and stability of the fabrication process. The sustained release of the loaded drugs from the nanoparticles indicated their suitability for controlled and prolonged drug delivery. Biocompatibility assessments revealed that the nanoparticles were nontoxic even at high concentrations and over extended periods. Moreover, the incorporation of statin within the nanoparticles enhanced the proliferative capacity and functional abilities of endothelial progenitor cells, thereby promoting angiogenesis and vascular repair. Co-administration of curcumin with statin further augmented the therapeutic effects by reducing intracellular reactive oxygen species levels and providing antioxidant protection against oxidative stress. Furthermore, we successfully integrated these nanoparticles into artificial blood vessels (ABVs) using three-dimensional printing technology, creating customizable constructs capable of supporting vascular regeneration. The viability and proliferative capacity of cells within the ABVs were preserved, which has potential for targeted drug delivery and localized therapy. In in vivo models of hindlimb ischemia, transplantation of nanoparticle-loaded ABVs resulted in significant improvements in terms of recovery speed and blood flow. Histological analysis confirmed the enhanced expression of vascular-related markers, indicating improved angiogenesis. Collectively, our findings demonstrate the potential of statin/curcumin-loaded nanoparticles as a promising approach for vascular tissue engineering and regenerative medicine. These nanoparticles offer controlled drug delivery, biocompatibility, and enhanced regenerative properties, suggesting that they are valuable tools for promoting vascular regeneration and advancing therapeutic interventions for cardiovascular diseases. Further research is required to fully elucidate the mechanisms of action and optimize their clinical applications.
{"title":"3D-bioprinted cell-laden blood vessel with dual drug delivery nanoparticles for advancing vascular regeneration","authors":"Eun Ji Lee, Jaewoo Choi, Hye ji Lim, Deokhyeon Yoon, Dong Myoung Lee, Donggu Kang, Jeong-Seok Lee, Hojun Jeon, Kyeong Hyeon Lee, Yong-Il Shin, Sang-Cheol Han, W. Jang, Sang-Mo Kwon","doi":"10.36922/ijb.1857","DOIUrl":"https://doi.org/10.36922/ijb.1857","url":null,"abstract":"Vascular regeneration plays a critical role in the treatment of cardiovascular diseases and in tissue engineering applications. In this study, we fabricated and characterized statin/curcumin-loaded nanoparticles for potential applications in vascular regeneration. The nanoparticles exhibited consistent spherical shape and sizes, indicating reproducibility and stability of the fabrication process. The sustained release of the loaded drugs from the nanoparticles indicated their suitability for controlled and prolonged drug delivery. Biocompatibility assessments revealed that the nanoparticles were nontoxic even at high concentrations and over extended periods. Moreover, the incorporation of statin within the nanoparticles enhanced the proliferative capacity and functional abilities of endothelial progenitor cells, thereby promoting angiogenesis and vascular repair. Co-administration of curcumin with statin further augmented the therapeutic effects by reducing intracellular reactive oxygen species levels and providing antioxidant protection against oxidative stress. Furthermore, we successfully integrated these nanoparticles into artificial blood vessels (ABVs) using three-dimensional printing technology, creating customizable constructs capable of supporting vascular regeneration. The viability and proliferative capacity of cells within the ABVs were preserved, which has potential for targeted drug delivery and localized therapy. In in vivo models of hindlimb ischemia, transplantation of nanoparticle-loaded ABVs resulted in significant improvements in terms of recovery speed and blood flow. Histological analysis confirmed the enhanced expression of vascular-related markers, indicating improved angiogenesis. Collectively, our findings demonstrate the potential of statin/curcumin-loaded nanoparticles as a promising approach for vascular tissue engineering and regenerative medicine. These nanoparticles offer controlled drug delivery, biocompatibility, and enhanced regenerative properties, suggesting that they are valuable tools for promoting vascular regeneration and advancing therapeutic interventions for cardiovascular diseases. Further research is required to fully elucidate the mechanisms of action and optimize their clinical applications.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139533345","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}
Microfluidic spinning, which has recently emerged as an important approach to processing hydrogels, can handle the flow in the fluid channel and generate microfibers in a controlled and mild manner, and therefore, it is suitable for cell loading, long-term culture, and tissue engineering. In this study, we utilized three-dimensional (3D) printing technology to prepare microfluidic chip templates with different microchannel heights in a one-step manner and obtained microfluidic spinning and microfiber assembly microchips. Hollow calcium alginate (CaA)/gelatin methacrylate (GelMA) composite microfibers were successfully prepared using a microfluidic spinning microchip combined with different fluid-injection strategies. The obtained hollow microfibers had one, two, or three lumens, and different inclusions could be added to the fiber walls. Hollow microfibers with a single lumen were used to load human umbilical vein endothelial cells (HUVECs) and exhibited good cell compatibility and barrier functions. We constructed a neural model based on the HUVEC-loaded hollow microfibers using a customized 3D printer. Using this established neural model, we induced the neural differentiation of rat adrenal medullary pheochromocytoma cells (PC12) using nerve growth factor. Axonal length, tubulin expression, and related gene (GAP-43 and TH) expression in PC12 cells were assessed. The current findings underscore the potential of utilizing microfluidic spinning in in vitro blood–brain barrier simulation, neuropharmaceutical and toxin evaluation, and brain-on-a-chip construction.
微流体纺丝是近年来兴起的一种加工水凝胶的重要方法，它能以可控和温和的方式处理流体通道中的流动并生成微纤维，因此适用于细胞装载、长期培养和组织工程。在这项研究中，我们利用三维（3D）打印技术一步制备了不同微通道高度的微流体芯片模板，并获得了微流体纺丝和微纤维组装微芯片。利用微流体纺丝微芯片结合不同的液体注入策略，成功制备了中空海藻酸钙（CaA）/甲基丙烯酸明胶（GelMA）复合微纤维。所制备的中空微纤维具有一个、两个或三个内腔，并可在纤维壁上添加不同的夹杂物。单腔中空微纤维用于负载人脐静脉内皮细胞（HUVEC），表现出良好的细胞相容性和屏障功能。我们使用定制的 3D 打印机，在装载了 HUVEC 的空心微纤维的基础上构建了一个神经模型。利用这一已建立的神经模型，我们使用神经生长因子诱导了大鼠肾上腺髓质嗜铬细胞瘤细胞（PC12）的神经分化。我们对 PC12 细胞的轴突长度、管蛋白表达和相关基因（GAP-43 和 TH）表达进行了评估。目前的研究结果凸显了利用微流体纺丝技术进行体外血脑屏障模拟、神经药物和毒素评估以及构建脑芯片的潜力。
{"title":"Preparation of tunable hollow composite microfibers assisted by microfluidic spinning and its application in the construction of in vitro neural models","authors":"Jingyun Ma, Wei Li, Li Tian, Xinghua Gao","doi":"10.36922/ijb.1797","DOIUrl":"https://doi.org/10.36922/ijb.1797","url":null,"abstract":"Microfluidic spinning, which has recently emerged as an important approach to processing hydrogels, can handle the flow in the fluid channel and generate microfibers in a controlled and mild manner, and therefore, it is suitable for cell loading, long-term culture, and tissue engineering. In this study, we utilized three-dimensional (3D) printing technology to prepare microfluidic chip templates with different microchannel heights in a one-step manner and obtained microfluidic spinning and microfiber assembly microchips. Hollow calcium alginate (CaA)/gelatin methacrylate (GelMA) composite microfibers were successfully prepared using a microfluidic spinning microchip combined with different fluid-injection strategies. The obtained hollow microfibers had one, two, or three lumens, and different inclusions could be added to the fiber walls. Hollow microfibers with a single lumen were used to load human umbilical vein endothelial cells (HUVECs) and exhibited good cell compatibility and barrier functions. We constructed a neural model based on the HUVEC-loaded hollow microfibers using a customized 3D printer. Using this established neural model, we induced the neural differentiation of rat adrenal medullary pheochromocytoma cells (PC12) using nerve growth factor. Axonal length, tubulin expression, and related gene (GAP-43 and TH) expression in PC12 cells were assessed. The current findings underscore the potential of utilizing microfluidic spinning in in vitro blood–brain barrier simulation, neuropharmaceutical and toxin evaluation, and brain-on-a-chip construction.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626389","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}
Hsuan-Wen Wang, Chih-Hwa Chen, Kuan-Hao Chen, Yu-Hui Zeng, Chun-Li Lin
Metal three-dimensional (3D) printing has become an important manufacturing process in medical implant development. Nevertheless, the metal 3D-printed implant needs to be considered with structural optimization to reduce the stress-shielding effects and to be incorporated with a lattice design to generate better bone ingrowth environment. This study combines topology optimization (TO) and lattice design to acquire an optimal wedge-shaped spacer (OWS) for high tibial osteotomy (HTO) fixation. The OWS was manufactured using titanium alloy 3D printing to conduct biomechanical fatigue testing for mechanical performance validation. A solid wedge-shaped spacer (SWS) with three embedded screws was designed using the HTO model. An OWS was obtained under physiological loads through finite element (FE) analysis and TO. A deformed YM lattice with a porosity of 60% and pore size of 700 μm was filled at the OWS posterior region. The HTO mechanical performance was simulated for SWS, OWS, and commercial T-shaped plate (TP) fixations using FE analysis. The displacement/fracture patterns under OWS and TP fixations were verified using fatigue testing. The manufacturing errors for all 3D-printed OWS features were found to be less than 1%. The FE results revealed that the OWS fixation demonstrated reductions of 56.46%, 11.98%, and 64.31% in displacement, stress in the implant and bone, respectively, compared to the TP fixation. The fatigue test indicated that the OWS fixation exhibited smaller displacement for the HTO, as well as a higher load capacity, minor bone fracture collapse, and a greater number of cycles than the TP system. This study concluded that medical implants can be designed by integrating macro TO and microlattice design to provide enough mechanical strength and an environment for bone ingrowth after surgery. Both FE analysis and biomechanical fatigue tests confirmed that OWS mechanical performance with lattice design was more stable than the HTO TP fixations.
金属三维（3D）打印已成为医疗植入物开发的重要制造工艺。然而，金属三维打印植入物需要考虑结构优化，以减少应力屏蔽效应，并与晶格设计相结合，以产生更好的骨生长环境。本研究将拓扑优化（TO）和晶格设计相结合，以获得用于高胫骨截骨术（HTO）固定的最佳楔形垫片（OWS）。OWS 采用钛合金 3D 打印技术制造，并进行了生物力学疲劳测试，以验证其机械性能。利用 HTO 模型设计了带有三个嵌入螺钉的实心楔形垫片（SWS）。通过有限元（FE）分析和 TO，获得了生理负荷下的 OWS。在 OWS 后部区域填充了孔隙率为 60%、孔径为 700 μm 的变形 YM 晶格。利用有限元分析模拟了 SWS、OWS 和商用 T 型钢板（TP）固定的 HTO 机械性能。通过疲劳测试验证了 OWS 和 TP 固定下的位移/断裂模式。所有 3D 打印 OWS 特征的制造误差均小于 1%。有限元分析结果显示，与 TP 固定相比，OWS 固定的位移、植入体和骨的应力分别减少了 56.46%、11.98% 和 64.31%。疲劳测试表明，与 TP 系统相比，OWS 固定器的 HTO 位移更小，承载能力更高，骨骨折塌陷更小，循环次数更多。这项研究得出结论，医疗植入物可以通过整合宏观 TO 和微格设计来提供足够的机械强度和术后骨生长环境。有限元分析和生物力学疲劳测试均证实，采用晶格设计的 OWS 机械性能比 HTO TP 固定装置更稳定。
{"title":"Designing a 3D-printed medical implant with mechanically macrostructural topology and microbionic lattices: A novel wedge-shaped spacer for high tibial osteotomy and biomechanical study","authors":"Hsuan-Wen Wang, Chih-Hwa Chen, Kuan-Hao Chen, Yu-Hui Zeng, Chun-Li Lin","doi":"10.36922/ijb.1584","DOIUrl":"https://doi.org/10.36922/ijb.1584","url":null,"abstract":"Metal three-dimensional (3D) printing has become an important manufacturing process in medical implant development. Nevertheless, the metal 3D-printed implant needs to be considered with structural optimization to reduce the stress-shielding effects and to be incorporated with a lattice design to generate better bone ingrowth environment. This study combines topology optimization (TO) and lattice design to acquire an optimal wedge-shaped spacer (OWS) for high tibial osteotomy (HTO) fixation. The OWS was manufactured using titanium alloy 3D printing to conduct biomechanical fatigue testing for mechanical performance validation. A solid wedge-shaped spacer (SWS) with three embedded screws was designed using the HTO model. An OWS was obtained under physiological loads through finite element (FE) analysis and TO. A deformed YM lattice with a porosity of 60% and pore size of 700 μm was filled at the OWS posterior region. The HTO mechanical performance was simulated for SWS, OWS, and commercial T-shaped plate (TP) fixations using FE analysis. The displacement/fracture patterns under OWS and TP fixations were verified using fatigue testing. The manufacturing errors for all 3D-printed OWS features were found to be less than 1%. The FE results revealed that the OWS fixation demonstrated reductions of 56.46%, 11.98%, and 64.31% in displacement, stress in the implant and bone, respectively, compared to the TP fixation. The fatigue test indicated that the OWS fixation exhibited smaller displacement for the HTO, as well as a higher load capacity, minor bone fracture collapse, and a greater number of cycles than the TP system. This study concluded that medical implants can be designed by integrating macro TO and microlattice design to provide enough mechanical strength and an environment for bone ingrowth after surgery. Both FE analysis and biomechanical fatigue tests confirmed that OWS mechanical performance with lattice design was more stable than the HTO TP fixations.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139441148","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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