Chenxi Peng, Phuong Tran, Simon Lalor, Oren Tirosh, Erich Rutz
Ankle-foot orthoses (AFOs) are frequently prescribed for children with cerebral palsy (CP) to correct specific features of abnormal gait. However, traditional AFO manufacturing and design involve labor-intensive processes and rely on subjective evaluations of clinicians. Recent advances in three-dimensional (3D) printing allow the rapid prototyping of AFOs, but the expanded design options complicate decision-making. This study aims to evaluate how AFO design affects the mechanical responses of 3D-printed AFOs. The lower limb geometry is established by a 3D-scanning system, and a prototypical AFO is designed, 3D printed, and tested under compression. A parametric study on the effect of base materials, thickness, and trimline location is conducted based on a validated numerical model. The results reveal that AFOs exhibit distinct behaviors under plantarflexion and dorsiflexion motions, with AFO stiffness correlating to thickness through a power function. AFO stiffness is more sensitive to posterior trim depth than inferior, while both trim depths significantly influence stress concentration around the ankle region. This investigation demonstrates the potential of combining 3D printing and computational modeling to improve the design and fabrication process of AFOs, providing insights into the development and customization of 3D-printed AFOs.
踝足矫形器（AFO）经常被用于矫正脑性麻痹（CP）儿童异常步态的特定特征。然而，传统的踝足矫形器制造和设计涉及劳动密集型流程，并且依赖于临床医生的主观评价。三维（3D）打印技术的最新进展允许快速制作 AFO 原型，但设计选项的扩大使决策变得更加复杂。本研究旨在评估 AFO 设计如何影响 3D 打印 AFO 的机械反应。通过三维扫描系统确定下肢几何形状，并设计、三维打印和测试原型 AFO。根据经过验证的数值模型，对基底材料、厚度和修剪线位置的影响进行了参数研究。研究结果表明，AFO 在跖屈和背屈运动下表现出不同的行为，AFO 的刚度与厚度通过幂函数相关。AFO 刚度对后修剪深度的敏感度高于下修剪深度，而两种修剪深度都会显著影响踝关节周围的应力集中。这项研究展示了将 3D 打印和计算建模相结合以改进 AFO 设计和制造过程的潜力，为 3D 打印 AFO 的开发和定制提供了启示。
{"title":"Tuning the mechanical responses of 3D-printed ankle-foot orthoses: A numerical study","authors":"Chenxi Peng, Phuong Tran, Simon Lalor, Oren Tirosh, Erich Rutz","doi":"10.36922/ijb.3390","DOIUrl":"https://doi.org/10.36922/ijb.3390","url":null,"abstract":"Ankle-foot orthoses (AFOs) are frequently prescribed for children with cerebral palsy (CP) to correct specific features of abnormal gait. However, traditional AFO manufacturing and design involve labor-intensive processes and rely on subjective evaluations of clinicians. Recent advances in three-dimensional (3D) printing allow the rapid prototyping of AFOs, but the expanded design options complicate decision-making. This study aims to evaluate how AFO design affects the mechanical responses of 3D-printed AFOs. The lower limb geometry is established by a 3D-scanning system, and a prototypical AFO is designed, 3D printed, and tested under compression. A parametric study on the effect of base materials, thickness, and trimline location is conducted based on a validated numerical model. The results reveal that AFOs exhibit distinct behaviors under plantarflexion and dorsiflexion motions, with AFO stiffness correlating to thickness through a power function. AFO stiffness is more sensitive to posterior trim depth than inferior, while both trim depths significantly influence stress concentration around the ankle region. This investigation demonstrates the potential of combining 3D printing and computational modeling to improve the design and fabrication process of AFOs, providing insights into the development and customization of 3D-printed AFOs.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141374447","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}
Mahyar Erfanian, Ahad Mohammadi, H. Ebrahimi Orimi, J. Zapata-Farfan, Joe Saade, Michel Meunier, Bruno Larrivée, C. Boutopoulos
We present a drop-on-demand (DOD) bioprinting method based on a novel implementation of laser-induced side transfer (LIST). Our approach involves continuous bioink perfusion through a glass capillary featuring a laser-machined hole in the capillary wall, serving as a nozzle. Focused low-energy nanosecond laser pulses are employed for precise droplet ejection. This innovative design separates the control of the bioink flow rate inside the capillary from the printing rate (drop ejection), leading to an enhanced printing workflow. We assessed the impact of key printing parameters, such as laser energy and flow conditions, on printing quality. Furthermore, we utilized the redesigned LIST to bioprint human umbilical vein endothelial cells (HUVECs). Our findings indicate that the printed HUVECs exhibit no viability loss and demonstrate the ability to recruit perivascular cells, including pericytes and fibroblasts. The redesigned LIST can be utilized in tissue engineering applications requiring DOD cell printing.
我们介绍了一种基于激光诱导侧转移（LIST）新方法的按需滴注（DOD）生物打印方法。我们的方法是通过玻璃毛细管持续灌注生物墨水，毛细管壁上的激光加工孔可作为喷嘴。聚焦的低能量纳秒激光脉冲用于液滴的精确喷射。这种创新设计将毛细管内生物墨水流速的控制与打印速度（液滴喷射）分开，从而改进了打印工作流程。我们评估了激光能量和流动条件等关键打印参数对打印质量的影响。此外，我们还利用重新设计的 LIST 对人脐静脉内皮细胞（HUVEC）进行了生物打印。我们的研究结果表明，打印出的 HUVECs 没有出现存活率下降的现象，并显示出招募血管周围细胞（包括周细胞和成纤维细胞）的能力。重新设计的 LIST 可用于需要 DOD 细胞打印的组织工程应用中。
{"title":"Drop-on-demand bioprinting: A redesigned laser-induced side transfer approach with continuous capillary perfusion","authors":"Mahyar Erfanian, Ahad Mohammadi, H. Ebrahimi Orimi, J. Zapata-Farfan, Joe Saade, Michel Meunier, Bruno Larrivée, C. Boutopoulos","doi":"10.36922/ijb.2832","DOIUrl":"https://doi.org/10.36922/ijb.2832","url":null,"abstract":"We present a drop-on-demand (DOD) bioprinting method based on a novel implementation of laser-induced side transfer (LIST). Our approach involves continuous bioink perfusion through a glass capillary featuring a laser-machined hole in the capillary wall, serving as a nozzle. Focused low-energy nanosecond laser pulses are employed for precise droplet ejection. This innovative design separates the control of the bioink flow rate inside the capillary from the printing rate (drop ejection), leading to an enhanced printing workflow. We assessed the impact of key printing parameters, such as laser energy and flow conditions, on printing quality. Furthermore, we utilized the redesigned LIST to bioprint human umbilical vein endothelial cells (HUVECs). Our findings indicate that the printed HUVECs exhibit no viability loss and demonstrate the ability to recruit perivascular cells, including pericytes and fibroblasts. The redesigned LIST can be utilized in tissue engineering applications requiring DOD cell printing.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141382181","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}
Mattia Spedicati, Francesca Tivano, Alice Zoso, Janira Bei, Mario Lavella, Irene Carmagnola, Valeria Chiono
Human cardiac fibrotic tissues are characterized by a higher stiffness relative to healthy cardiac tissues. These tissues are unable to spontaneously contract and are subjected to passive mechanical stimulation during heart functionality. Moreover, scaffolds that can recapitulate the in vivo mechanical properties of the cardiac fibrotic tissues are lacking. Herein, this study aimed to design and fabricate mechanically stretchable bioartificial scaffolds with biomimetic composition and stiffness comparable to human cardiac fibrotic tissues. Poly(ε-caprolactone) (PCL) scaffolds with a stretchable mesh architecture were initially designed through structural and finite element method (FEM) analyses and subsequently fabricated by melt extrusion additive manufacturing (MEX). Scaffolds were surface functionalized by 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization (polyDOPA) to improve their interaction with natural polymers. Scaffold pores were then filled with different concentrations (5%, 7%, and 10% w/v) of gelatin methacryloyl (GelMA) hydrogels to support in vitro human cardiac fibroblasts (HCFs) 3D culture, thereby producing bioartificial PCL/GelMA scaffolds. Uniaxial tensile mechanical tests in static and dynamic conditions (1 Hz; 22% maximum strain) demonstrated that the bioartificial scaffolds had in vivo-like stretchability and similar stiffness to that of pathological cardiac tissue (tailored as a function of the number of PCL scaffold layers and GelMA hydrogel concentration). In vitro cell tests on bioartificial scaffolds using HCF-embedded GelMA hydrogels under static conditions displayed increasing cell viability, spreading, and cytoskeleton organization with decreasing GelMA hydrogel concentration. Moreover, α-smooth muscle actin (α-SMA)-positive cells were detected after 7 days of culture in static conditions followed by another 7 days of culture in dynamic conditions and not in HCF-loaded scaffolds cultured in static conditions for 14 days. These results suggested that in vitro culture under cyclic mechanical stimulations could induce an HCF phenotypic switch into myofibroblasts.
{"title":"3D bioartificial stretchable scaffolds mimicking the mechanical hallmarks of human cardiac fibrotic tissue","authors":"Mattia Spedicati, Francesca Tivano, Alice Zoso, Janira Bei, Mario Lavella, Irene Carmagnola, Valeria Chiono","doi":"10.36922/ijb.2247","DOIUrl":"https://doi.org/10.36922/ijb.2247","url":null,"abstract":"Human cardiac fibrotic tissues are characterized by a higher stiffness relative to healthy cardiac tissues. These tissues are unable to spontaneously contract and are subjected to passive mechanical stimulation during heart functionality. Moreover, scaffolds that can recapitulate the in vivo mechanical properties of the cardiac fibrotic tissues are lacking. Herein, this study aimed to design and fabricate mechanically stretchable bioartificial scaffolds with biomimetic composition and stiffness comparable to human cardiac fibrotic tissues. Poly(ε-caprolactone) (PCL) scaffolds with a stretchable mesh architecture were initially designed through structural and finite element method (FEM) analyses and subsequently fabricated by melt extrusion additive manufacturing (MEX). Scaffolds were surface functionalized by 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization (polyDOPA) to improve their interaction with natural polymers. Scaffold pores were then filled with different concentrations (5%, 7%, and 10% w/v) of gelatin methacryloyl (GelMA) hydrogels to support in vitro human cardiac fibroblasts (HCFs) 3D culture, thereby producing bioartificial PCL/GelMA scaffolds. Uniaxial tensile mechanical tests in static and dynamic conditions (1 Hz; 22% maximum strain) demonstrated that the bioartificial scaffolds had in vivo-like stretchability and similar stiffness to that of pathological cardiac tissue (tailored as a function of the number of PCL scaffold layers and GelMA hydrogel concentration). In vitro cell tests on bioartificial scaffolds using HCF-embedded GelMA hydrogels under static conditions displayed increasing cell viability, spreading, and cytoskeleton organization with decreasing GelMA hydrogel concentration. Moreover, α-smooth muscle actin (α-SMA)-positive cells were detected after 7 days of culture in static conditions followed by another 7 days of culture in dynamic conditions and not in HCF-loaded scaffolds cultured in static conditions for 14 days. These results suggested that in vitro culture under cyclic mechanical stimulations could induce an HCF phenotypic switch into myofibroblasts.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140973293","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}
The current hydrogel self-inflating expander is limited by its volume and linear expansion rate, making it unsuitable for correcting patient-specific large mandibular bone defects in soft-tissue surgeries. This study devised a novel approach for crafting patient-specific gingival tissue expanders for large mandibular bone defects by employing silicone 3D-printing technology. The biocompatible and swellable polymer tablet was compressed and placed into a 3D-printed silicone membrane to evaluate its expansion capability. Two patient-specific large left and right mandibular bone defects with complex geometries were selected to generate defect expander models in a computer-aided design (CAD) software. The swellable tablets were enveloped in the 3D-printed silicone membranes to form soft-tissue expanders, which were then immersed in phosphate-buffered saline (PBS) for 6 weeks to observe their expansion. Results demonstrated that a slot-shaped silicone soft-tissue tablet attained an expansion volume of 1960 mm³. A fourth-degree polynomial fitting curve illustrated slower expansion rates in the initial 2 weeks and achieved complete expansion in about 6 weeks. Patient-specific silicone expander testing indicated less than 2% error in the average expanded volumes of compared to CAD models. The cross-sectional profile of the soft-tissue expanders closely resembled the CAD model. This study demonstrated that biocompatible polymer could be utilized as swellable tablet material and enveloped within a 3D-printed silicone membrane to generate a novel soft-tissue expander that adhered to clinical standards. Additionally, the study validated the feasibility of expanding patient-specific silicone expanders within 6 weeks for repairing large left and right mandibular bone defects.
目前的水凝胶自充气扩张器受限于其体积和线性扩张率，不适合在软组织手术中矫正患者特异性大面积下颌骨缺损。本研究采用硅胶三维打印技术，设计了一种新方法，用于制作患者特异性牙龈组织扩张器，以治疗大面积下颌骨缺损。将具有生物相容性和可膨胀性的聚合物片剂压缩并放入 3D 打印的硅胶膜中，以评估其膨胀能力。研究人员选择了两个具有复杂几何形状的患者特异性左右下颌骨大缺损，在计算机辅助设计（CAD）软件中生成缺损扩张器模型。将可膨胀药片包裹在 3D 打印的硅胶膜中，形成软组织扩张器，然后将其浸泡在磷酸盐缓冲盐水（PBS）中 6 周，观察其扩张情况。结果表明，槽形硅胶软组织片的膨胀体积达到了 1960 立方毫米。四度多项式拟合曲线显示，最初两周的膨胀速度较慢，大约 6 周后膨胀完全。针对患者的硅胶扩张器测试表明，与 CAD 模型相比，平均扩张体积误差小于 2%。软组织扩张器的横截面轮廓与 CAD 模型非常相似。这项研究表明，生物相容性聚合物可用作膨胀片剂材料，并包裹在三维打印的硅胶膜中，生成符合临床标准的新型软组织扩张器。此外，该研究还验证了在 6 周内将患者特制的硅胶扩张器扩张用于修复左右下颌骨大面积缺损的可行性。
{"title":"Novel patient-specific gingival soft-tissue expander development for large bone defects using silicone 3D-printing technology","authors":"Tzu-Huan Huang, Shao-Fu Huang, Lu-Yi Yu, Chun-Liang Lo, Yu-Ping Chang, Chun-Li Lin","doi":"10.36922/ijb.2918","DOIUrl":"https://doi.org/10.36922/ijb.2918","url":null,"abstract":"The current hydrogel self-inflating expander is limited by its volume and linear expansion rate, making it unsuitable for correcting patient-specific large mandibular bone defects in soft-tissue surgeries. This study devised a novel approach for crafting patient-specific gingival tissue expanders for large mandibular bone defects by employing silicone 3D-printing technology. The biocompatible and swellable polymer tablet was compressed and placed into a 3D-printed silicone membrane to evaluate its expansion capability. Two patient-specific large left and right mandibular bone defects with complex geometries were selected to generate defect expander models in a computer-aided design (CAD) software. The swellable tablets were enveloped in the 3D-printed silicone membranes to form soft-tissue expanders, which were then immersed in phosphate-buffered saline (PBS) for 6 weeks to observe their expansion. Results demonstrated that a slot-shaped silicone soft-tissue tablet attained an expansion volume of 1960 mm³. A fourth-degree polynomial fitting curve illustrated slower expansion rates in the initial 2 weeks and achieved complete expansion in about 6 weeks. Patient-specific silicone expander testing indicated less than 2% error in the average expanded volumes of compared to CAD models. The cross-sectional profile of the soft-tissue expanders closely resembled the CAD model. This study demonstrated that biocompatible polymer could be utilized as swellable tablet material and enveloped within a 3D-printed silicone membrane to generate a novel soft-tissue expander that adhered to clinical standards. Additionally, the study validated the feasibility of expanding patient-specific silicone expanders within 6 weeks for repairing large left and right mandibular bone defects.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140992314","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}
Zinc–magnesium (Zn–Mg) alloys, fabricated by laser powder bed fusion (LPBF) additive manufacturing techniques, have emerged as promising candidates for biomedical implants due to their biodegradation capability, superior mechanical strength, and excellent biocompatibility. However, LPBF-fabricated Zn–Mg alloys still face challenges related to extremely low ductility and limited exploration of degradation characteristics. In this study, the impact of Mg incorporation on the printability, degradation properties, microstructure, and mechanical properties of LPBF-fabricated Zn–Mg alloys was primarily investigated. Furthermore, we proposed a viable annealing post-processing route for the first time to tailor the microstructural characteristics of the fabricated Zn–Mg alloy and enhanced its limited ductility. The results demonstrated that by applying a laser power of 80 W and a scanning speed of 600 mm/s, the relative density of LPBF-fabricated Zn–Mg alloy reached 98.62%. Increasing the Mg amount from 1 to 5 wt% refined the grain size while promoting an increase in Mg2Zn11 and MgZn2 phases. Among these compositions, the Zn–1Mg alloy exhibited the greatest degradation rate at 0.126 mm/year. The annealing treatment facilitated the microstructure evolution of the Zn–1Mg alloy, resulting in equiaxed grains, increased average grain size, high-angle grain boundaries, and enrichment of Mg at grain boundaries. After annealing at 300°C for 0.5 h, the tensile strength of Zn– 1Mg alloy decreased from 254.92 to 170.93 MPa, while the elongation significantly increased by a factor of 14.3 from 0.55% to 8.43%. These findings provide valuable insights into an effective post-processing approach for tailoring the microstructure and resultant mechanical properties of LPBF-fabricated Zn and its alloys.
{"title":"Microstructure evolution and ductility improvement of additively manufactured biodegradable zinc–magnesium alloys via annealing","authors":"Changjun Han, Jinmiao Huang, Xiangling Ye, Boxun Liu, Zhi Dong, Yongqiang Yang, Junqing Gao, Kuangyang Yang, Guocai Chen","doi":"10.36922/ijb.3034","DOIUrl":"https://doi.org/10.36922/ijb.3034","url":null,"abstract":"Zinc–magnesium (Zn–Mg) alloys, fabricated by laser powder bed fusion (LPBF) additive manufacturing techniques, have emerged as promising candidates for biomedical implants due to their biodegradation capability, superior mechanical strength, and excellent biocompatibility. However, LPBF-fabricated Zn–Mg alloys still face challenges related to extremely low ductility and limited exploration of degradation characteristics. In this study, the impact of Mg incorporation on the printability, degradation properties, microstructure, and mechanical properties of LPBF-fabricated Zn–Mg alloys was primarily investigated. Furthermore, we proposed a viable annealing post-processing route for the first time to tailor the microstructural characteristics of the fabricated Zn–Mg alloy and enhanced its limited ductility. The results demonstrated that by applying a laser power of 80 W and a scanning speed of 600 mm/s, the relative density of LPBF-fabricated Zn–Mg alloy reached 98.62%. Increasing the Mg amount from 1 to 5 wt% refined the grain size while promoting an increase in Mg2Zn11 and MgZn2 phases. Among these compositions, the Zn–1Mg alloy exhibited the greatest degradation rate at 0.126 mm/year. The annealing treatment facilitated the microstructure evolution of the Zn–1Mg alloy, resulting in equiaxed grains, increased average grain size, high-angle grain boundaries, and enrichment of Mg at grain boundaries. After annealing at 300°C for 0.5 h, the tensile strength of Zn– 1Mg alloy decreased from 254.92 to 170.93 MPa, while the elongation significantly increased by a factor of 14.3 from 0.55% to 8.43%. These findings provide valuable insights into an effective post-processing approach for tailoring the microstructure and resultant mechanical properties of LPBF-fabricated Zn and its alloys.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140998268","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}
Qinghua Liu, Yu Feng, B. Yao, Zhao Li, Yi Kong, Chao Zhang, Yaxin Tan, W. Song, Jirigala Enhe, Xiaohe Li, Sha Huang
Tissue engineering is an approach used to restore damaged tissues and organs using biomaterials that support cell adhesion, growth, and proliferation. However, immune responses triggered by tissue injury and biomaterial implantation can lead to undesired reactions such as foreign body response and fibrotic capsule formation. Macrophages play a critical role in these immune responses. Therefore, comprehending and controlling the immune responses to biomaterials are crucial for successful clinical translation in tissue engineering. In this experimental study, we fabricated three-dimensional-bioprinted hydrogel scaffolds with adaptable stiffness by adjusting the alginate–gelatin ratio. We examined the physical properties of these scaffolds and assessed the immune responses they provoked both in vitro and in vivo. Our results revealed that higher-stiffness implants could drive macrophage polarization toward pro-inflammatory phenotypes in vivo. Furthermore, our animal experiments demonstrated that high-stiffness hydrogels elicited elevated immune responses through the TLR4/Myd88/NF-κB signaling pathway and IL-6/JAK-STAT signaling pathway. Collectively, our study demonstrates that increased implant stiffness correlates with stronger immune responses. These findings are expected to provide novel insights for the clinical application of alginate–gelatin composite hydrogels.
{"title":"Effect of tunable stiffness on immune responses in 3D-bioprinted alginate–gelatin scaffolds","authors":"Qinghua Liu, Yu Feng, B. Yao, Zhao Li, Yi Kong, Chao Zhang, Yaxin Tan, W. Song, Jirigala Enhe, Xiaohe Li, Sha Huang","doi":"10.36922/ijb.2874","DOIUrl":"https://doi.org/10.36922/ijb.2874","url":null,"abstract":"Tissue engineering is an approach used to restore damaged tissues and organs using biomaterials that support cell adhesion, growth, and proliferation. However, immune responses triggered by tissue injury and biomaterial implantation can lead to undesired reactions such as foreign body response and fibrotic capsule formation. Macrophages play a critical role in these immune responses. Therefore, comprehending and controlling the immune responses to biomaterials are crucial for successful clinical translation in tissue engineering. In this experimental study, we fabricated three-dimensional-bioprinted hydrogel scaffolds with adaptable stiffness by adjusting the alginate–gelatin ratio. We examined the physical properties of these scaffolds and assessed the immune responses they provoked both in vitro and in vivo. Our results revealed that higher-stiffness implants could drive macrophage polarization toward pro-inflammatory phenotypes in vivo. Furthermore, our animal experiments demonstrated that high-stiffness hydrogels elicited elevated immune responses through the TLR4/Myd88/NF-κB signaling pathway and IL-6/JAK-STAT signaling pathway. Collectively, our study demonstrates that increased implant stiffness correlates with stronger immune responses. These findings are expected to provide novel insights for the clinical application of alginate–gelatin composite hydrogels.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140746202","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}
Daniel Nieto, Alberto Jorge de Mora, Maria Kalogeropoulou, Anant Bhusal, Amir K. Miri, Lorenzo Moroni
Over the years, three-dimensional (3D) bioprinting has attracted attention for being a highly automated manufacturing system that allows for the precise design of living constructs where cells and biomaterials are displaced in predefined positions to recreate cell–matrix and cell–cell interactions similar to native tissues. Such technologies rarely offer multi-material features. In this paper, we present a new approach for bioprinting of multi-material tissue constructs using VAT photopolymerization at high resolution and fidelity. We developed a versatile dual-mode bioprinter that can easily be modulated to print in both top-down and bottom-up approaches. The custom-built platform was then used to fabricate microtissues and hydrogel microfluidic models. Combining bottom-up and top-down biofabrication tools can offer an optimal solution for hard–soft multi-material composites and for bioprinting tissue–tissue interface models. We demonstrated the possibility for hard–soft multi-material bioprinting by generating musculoskeletal tissue with integrated microvasculature. Combining multiple material bioprinting and microfluidic chips shows advantages in two aspects: precise regulation of microenvironment and accurate emulation of multi-tissue interfaces.
{"title":"Bottom-up and top-down VAT photopolymerization bioprinting for rapid fabrication of multi-material microtissues","authors":"Daniel Nieto, Alberto Jorge de Mora, Maria Kalogeropoulou, Anant Bhusal, Amir K. Miri, Lorenzo Moroni","doi":"10.36922/ijb.1017","DOIUrl":"https://doi.org/10.36922/ijb.1017","url":null,"abstract":"Over the years, three-dimensional (3D) bioprinting has attracted attention for being a highly automated manufacturing system that allows for the precise design of living constructs where cells and biomaterials are displaced in predefined positions to recreate cell–matrix and cell–cell interactions similar to native tissues. Such technologies rarely offer multi-material features. In this paper, we present a new approach for bioprinting of multi-material tissue constructs using VAT photopolymerization at high resolution and fidelity. We developed a versatile dual-mode bioprinter that can easily be modulated to print in both top-down and bottom-up approaches. The custom-built platform was then used to fabricate microtissues and hydrogel microfluidic models. Combining bottom-up and top-down biofabrication tools can offer an optimal solution for hard–soft multi-material composites and for bioprinting tissue–tissue interface models. We demonstrated the possibility for hard–soft multi-material bioprinting by generating musculoskeletal tissue with integrated microvasculature. Combining multiple material bioprinting and microfluidic chips shows advantages in two aspects: precise regulation of microenvironment and accurate emulation of multi-tissue interfaces.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140752428","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}
S. Ruiz-Alonso, Jorge Ordoyo-Pascual, M. Lafuente-Merchan, Fátima García-Villén, Myriam Sainz-Ramos, Idoia Gallego, Laura Saenz- Del-Burgo, Jose L. Pedraz
In the evolving field of tissue engineering, the power of three-dimensional (3D) bioprinting technology can be harnessed by innovative methodologies to address the complex challenges of treating partial tendon injuries. In order to engineer a solution for this type of musculoskeletal injuries, a biomimetic bioink and a scaffold developed using 3D bioprinting technology and capable of delivering cells and growth factors were investigated. For the development of the bioink, a hydrogel type structure was selected based on a strategic combination of alginate, hyaluronic acid, gelatin, and fibrinogen. This tailored combination exhibited favorable rheological behavior and impeccable printability. The bioink, demonstrating promising characteristics, was then employed to fabricate both acellular scaffolds and tissue constructs. The structures possessed mechanical properties suitable and adequate for addressing partial tendon injuries and achieved a microenvironment that allowed good metabolic activity of tenocytes, maintenance of their phenotype, and overexpression of genes related to macromolecules of tendon extracellular matrix. Regarding growth factors delivery, vascular endothelial growth factor (VEGF165) and platelet-derived growth factor (PDGF-BB) were successfully incorporated into the bioink. Their release profile was thoroughly studied, and their activity once released was demonstrated. Together, these results suggest that the developed bioink and the resulting 3D structures can have an important impact on tendon partial injury therapies. The multifaceted capabilities of the bioink and the developed tissue constructs position them as crucial contributors to the advancement of tendon injury therapies, marking a significant stride toward enhanced patient outcomes and regenerative medicine practices.
{"title":"Hydrogel bioink formulation for 3D bioprinting: Sustained delivery of PDGF-BB and VEGF in biomimetic scaffolds for tendon partial rupture repair","authors":"S. Ruiz-Alonso, Jorge Ordoyo-Pascual, M. Lafuente-Merchan, Fátima García-Villén, Myriam Sainz-Ramos, Idoia Gallego, Laura Saenz- Del-Burgo, Jose L. Pedraz","doi":"10.36922/ijb.2632","DOIUrl":"https://doi.org/10.36922/ijb.2632","url":null,"abstract":"In the evolving field of tissue engineering, the power of three-dimensional (3D) bioprinting technology can be harnessed by innovative methodologies to address the complex challenges of treating partial tendon injuries. In order to engineer a solution for this type of musculoskeletal injuries, a biomimetic bioink and a scaffold developed using 3D bioprinting technology and capable of delivering cells and growth factors were investigated. For the development of the bioink, a hydrogel type structure was selected based on a strategic combination of alginate, hyaluronic acid, gelatin, and fibrinogen. This tailored combination exhibited favorable rheological behavior and impeccable printability. The bioink, demonstrating promising characteristics, was then employed to fabricate both acellular scaffolds and tissue constructs. The structures possessed mechanical properties suitable and adequate for addressing partial tendon injuries and achieved a microenvironment that allowed good metabolic activity of tenocytes, maintenance of their phenotype, and overexpression of genes related to macromolecules of tendon extracellular matrix. Regarding growth factors delivery, vascular endothelial growth factor (VEGF165) and platelet-derived growth factor (PDGF-BB) were successfully incorporated into the bioink. Their release profile was thoroughly studied, and their activity once released was demonstrated. Together, these results suggest that the developed bioink and the resulting 3D structures can have an important impact on tendon partial injury therapies. The multifaceted capabilities of the bioink and the developed tissue constructs position them as crucial contributors to the advancement of tendon injury therapies, marking a significant stride toward enhanced patient outcomes and regenerative medicine practices.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776253","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}
Viola Sgarminato, Michela Licciardello, G. Ciardelli, Chiara Tonda-Turo
Melt-electrowriting (MEW) belongs to the group of advanced additive manufacturing techniques and consists of computer-aided design (CAD)-assisted polymer extrusion combined with a high-voltage supply to achieve deposition of polymeric fibers with diameters in the micrometric range (1 to 20 μm) similar to the size of natural extracellular matrix fibers. In this work, we exploit MEW to design and fabricate a three-dimensional (3D) model that resembles the morphology of the exocrine pancreatic functional unit without the need of supports, mandrels, or sacrificial materials. Optimized process parameters resulted in a MEW scaffold having regular fibers (19 ± 5 μm size) and an acinar cavity showing high shape fidelity. Then, human foreskin fibroblasts (HFF1) and human pancreatic ductal epithelial cells (HPDE), wild-type HPDE, and HPDE overexpressing KRAS oncogene were allowed to colonize the entire 3D structure and the acinar cavity. Thus, a physiologically relevant 3D model was created in vitro after 24 days using a co-culture protocol (14 days of HFF1 alone plus 10 days of HPDE and HFF1 co-culture). The effect of cell crosstalk within the MEW scaffolds was also assessed by monitoring HFF1 secretion of interleukin (IL)-6, a pro-inflammatory cytokine responsible for the inflammatory cascade occurring in pancreatic cancer. High levels of IL-6 were detected only when fibroblasts were co-cultured with the HPDE overexpressing KRAS. These findings confirmed that the MEW 3D in vitro model is able to recreate the characteristic hallmark of the pathological condition where cancer oncogenes mediate fibroblast activities.
{"title":"Melt-electrowriting of 3D anatomically relevant scaffolds to recreate a pancreatic acinar unit in vitro","authors":"Viola Sgarminato, Michela Licciardello, G. Ciardelli, Chiara Tonda-Turo","doi":"10.36922/ijb.1975","DOIUrl":"https://doi.org/10.36922/ijb.1975","url":null,"abstract":"Melt-electrowriting (MEW) belongs to the group of advanced additive manufacturing techniques and consists of computer-aided design (CAD)-assisted polymer extrusion combined with a high-voltage supply to achieve deposition of polymeric fibers with diameters in the micrometric range (1 to 20 μm) similar to the size of natural extracellular matrix fibers. In this work, we exploit MEW to design and fabricate a three-dimensional (3D) model that resembles the morphology of the exocrine pancreatic functional unit without the need of supports, mandrels, or sacrificial materials. Optimized process parameters resulted in a MEW scaffold having regular fibers (19 ± 5 μm size) and an acinar cavity showing high shape fidelity. Then, human foreskin fibroblasts (HFF1) and human pancreatic ductal epithelial cells (HPDE), wild-type HPDE, and HPDE overexpressing KRAS oncogene were allowed to colonize the entire 3D structure and the acinar cavity. Thus, a physiologically relevant 3D model was created in vitro after 24 days using a co-culture protocol (14 days of HFF1 alone plus 10 days of HPDE and HFF1 co-culture). The effect of cell crosstalk within the MEW scaffolds was also assessed by monitoring HFF1 secretion of interleukin (IL)-6, a pro-inflammatory cytokine responsible for the inflammatory cascade occurring in pancreatic cancer. High levels of IL-6 were detected only when fibroblasts were co-cultured with the HPDE overexpressing KRAS. These findings confirmed that the MEW 3D in vitro model is able to recreate the characteristic hallmark of the pathological condition where cancer oncogenes mediate fibroblast activities.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140436832","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}
Repairing severe bone defects and restoring complete bone tissue morphology are major challenges in clinical practice. Biodegradable metals (BMs) are bioactive materials with active degradation properties. The gradual improvement of three-dimensional (3D) printing technology holds tremendous potential for development and has spurred on the growing utilization of 3D-printed BM materials in the clinical applications of bone regeneration. In this paper, we review the application of three BM (magnesium, iron, and zinc) materials for use in 3D-printed bone regeneration; define the principle of 3D-printed bone regeneration, including the method and selection of materials; and summarize the characteristics and uses of various printing technologies and the properties, advantages, and disadvantages of BMs. Compared to traditional nondegradable implants, 3D-printed degradable metal implants have the advantages of not leaving residue, avoiding stress shielding, promoting osteogenesis and vascularization, and exhibiting antimicrobial ability. In addition, we summarize the clinical applications of 3D-printed BMs. 3D-printed BMs can be used not only for fracture fixation and bone defect repair but also for osteoporotic fracture repair, cartilage repair, maxillofacial surgery, and other processes. In this article, we discuss the advantages and limitations of the current 3D printing degradable metallic materials and describe future development prospects.
修复严重的骨缺损和恢复完整的骨组织形态是临床实践中的主要挑战。生物降解金属（BMs）是一种具有活性降解特性的生物活性材料。三维（3D）打印技术的逐步完善蕴含着巨大的发展潜力，并促使三维打印 BM 材料在骨再生临床应用中的应用日益广泛。本文综述了三种BM（镁、铁和锌）材料在3D打印骨再生中的应用；明确了3D打印骨再生的原理，包括方法和材料的选择；总结了各种打印技术的特点和用途，以及BM的特性和优缺点。与传统的不可降解植入物相比，3D打印可降解金属植入物具有不残留、避免应力屏蔽、促进骨生成和血管化、抗菌能力强等优点。此外，我们还总结了三维打印生物材料的临床应用。三维打印基质不仅可用于骨折固定和骨缺损修复，还可用于骨质疏松性骨折修复、软骨修复、颌面外科手术等过程。本文讨论了目前 3D 打印可降解金属材料的优势和局限性，并阐述了未来的发展前景。
{"title":"Techniques, mechanisms, and application of 3D-printed biodegradable metals for bone regeneration","authors":"Lingxiao Wang, Yang Liu, Zhipeng Fan","doi":"10.36922/ijb.2460","DOIUrl":"https://doi.org/10.36922/ijb.2460","url":null,"abstract":"Repairing severe bone defects and restoring complete bone tissue morphology are major challenges in clinical practice. Biodegradable metals (BMs) are bioactive materials with active degradation properties. The gradual improvement of three-dimensional (3D) printing technology holds tremendous potential for development and has spurred on the growing utilization of 3D-printed BM materials in the clinical applications of bone regeneration. In this paper, we review the application of three BM (magnesium, iron, and zinc) materials for use in 3D-printed bone regeneration; define the principle of 3D-printed bone regeneration, including the method and selection of materials; and summarize the characteristics and uses of various printing technologies and the properties, advantages, and disadvantages of BMs. Compared to traditional nondegradable implants, 3D-printed degradable metal implants have the advantages of not leaving residue, avoiding stress shielding, promoting osteogenesis and vascularization, and exhibiting antimicrobial ability. In addition, we summarize the clinical applications of 3D-printed BMs. 3D-printed BMs can be used not only for fracture fixation and bone defect repair but also for osteoporotic fracture repair, cartilage repair, maxillofacial surgery, and other processes. In this article, we discuss the advantages and limitations of the current 3D printing degradable metallic materials and describe future development prospects.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140457979","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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