Biofabrication最新文献

{"title":"3D printed osteochondral lineage-specific biphasic scaffolds for functional repair of full-thickness articular cartilage defects in weight-bearing area.","authors":"Shengnan Qin, Wen Wang, Liang Chen, Ming Yu, Cailing Zhao, Haiquan Zeng, Hanyu Chu, Kexin Zhang, Simin Wu, Rui Cui, Yinfeng Zheng, Ying Bai, Jiake Xu","doi":"10.1088/1758-5090/ade8a9","DOIUrl":"https://doi.org/10.1088/1758-5090/ade8a9","url":null,"abstract":"<p><p>Functional repair of full-thickness defects in the weight-bearing articular cartilage has been one of the major challenges in orthopeadics. Whereas the advanced 3D printing technique allows the construction of bionic bioscaffolds that support in-situ tissue regeneration. Herein, we developed a sort of lineage-specific biphasic scaffolds for osteochondral regeneration, fabricated via consecutive 3D-printing and lyophilization. To facilitate osteogenesis and bone formation, a porous scaffold was 3D-printed fabricated using a composite ink consisting of gelatin methacrylate (GelMA) and hydroxyapatite (HAP). To synergistically stimulate chondrogenesis and hyaline cartilage regeneration, collagen was infused into the top layers of the 3D-printed GelMA/HAP construct. In vitro culture of bone marrow mesenchymal stem cells (BMSCs) showed that the top collagen layer preferentially promoted BMSCs chondrogenic differentiation, while the GelMA/HAP composite mostly contributed to their osteogenic differentiation. This customized biphasic scaffold was then examined within the defected weight-bearing regions of full-thickness articular cartilage in rabbits, in which neocartilage, bone formation and remodeling were identified at six and twelve weeks post-implantation. Consistently to the in vitro findings, the bottom GelMA/HAP scaffold facilitated bone formation, while the top-layer with preloaded collagen markedly augmented hyaline cartilage formation in vivo. Furthermore, it was evident that the biphasic scaffolds effectively modulated bone remodeling dynamics via inhibiting hyperactive osteoclast activities. Considering that such combinatorial biphasic scaffolds were easily prepared and successfully utilized for cartilage defect repair, this cell-free tissue-engineered strategy holds great promise in future clinical translation.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging transfer learning for efficient bioprinting.","authors":"F Bracco, G Zanderigo, K Paynabar, B M Colosimo","doi":"10.1088/1758-5090/ade62f","DOIUrl":"10.1088/1758-5090/ade62f","url":null,"abstract":"<p><p>Bioprinting is a promising family of processes combining 3D printing with life sciences, offering the potential to significantly advance various applications. Despite numerous research efforts aimed at enhancing process modeling, optimizing capabilities, and exploring new conditions, there remains a critical need to enhance process efficiency. Experimental data are paramount for improving models. Nevertheless, it is practically unfeasible to explore a multitude of conditions (e.g. different material formulations, process parameters, machines, setups), especially given the experimental constraints of budget and time. Leveraged by in-situ bioprinting monitoring, this paper explores a set of transfer learning (TL) methods designed for resource-efficient bioprinting modeling, aiming to merge established knowledge with new experimental conditions. TL encompasses machine learning strategies focused on transferring knowledge across distinct, yet similar, domains. TL is applied to an extrusion-based bioprinting case study for printability response modeling. The knowledge acquired from a model trained on one material (the source) is transferred to a new material (the target), under conditions of limited experimental data availability. Eventually, the accuracy of the transferred model is assessed and compared against a reference no-transfer scenario, which is developed from scratch following conventional practices. Furthermore, giving high importance to the experimental effort reduction, a sensitivity analysis altering the number of experimental training points is performed to assess performances and limitations of the method. This method demonstrates the feasibility of knowledge transfer in bioprinting as a catalyst for more sophisticated applications across diverse printing conditions, materials, and technologies to advancing this technology towards achieving its full potential.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intervertebral disc spheroids as an<i>in vitro</i>multicellular platform for recapitulating the microenvironment of intervertebral disc degeneration.","authors":"Tae-Won Kim, An-Gi Kim, Min-Ho Hwang, Hyuk Choi","doi":"10.1088/1758-5090/ade56c","DOIUrl":"10.1088/1758-5090/ade56c","url":null,"abstract":"<p><p>Intervertebral disc (IVD) degeneration (IVDD) is a major contributor to chronic low back pain, representing a substantial burden on the spinal healthcare system and serving as a leading cause of long-term disability worldwide. Biomimetic<i>in vitro</i>models that accurately replicate histological characteristics, three-dimensional structures, and multicellular interactions are lacking. Consequently, monocultures of cell lines and two-dimensional culture models are still used to study the pathomechanisms of IVDD. We established functional multicellular IVD spheroid cultures using primary human annulus fibrosus and nucleus pulposus cells. The spheroids maintained the IVD-specific phenotype, including hypoxic conditions and lamellar structures. Additionally, the spheroid markedly increased the expression level of inflammatory mediators and chemokines in the presence of the pro-inflammatory cytokine IL-1<i>β</i>, a master regulator of IVDD. Furthermore, we implemented our microfluidic chemotaxis platform to investigate microglial neuroinflammation in response to our reconstituted IVD spheroid models. Transcriptome sequencing revealed that microglia stimulated by potential contributing factors derived from IVDD spheroids exhibited a significant upregulation of the expression levels of chemotactic factors and cytokines including CCL-2, -3, -4, -5, IL-8 and IL-6 (<i>p</i>< 0.05). Moreover, we observed considerable activation and infiltration of microglia induced by soluble factors derived from IVDD spheroids, which are expected to occur during IVDD. The chemotactic effects on microglia were reduced upon the neutralization of CCL-2 or IL-8 or inhibition of NF-<i>κ</i>B signaling. These robust<i>in vitro</i>IVD spheroids can be used to model IVDD and provide a valuable platform for the assessment and development of IVDD therapeutics.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D bioprinted GelMA/collagen hydrogel for corneal stroma regeneration.","authors":"Yingni Xu, Wenfang Liu, Qi Zhao, Xiaoyan Feng, Zhibiao Li, Yongrui Huang, Jia Liu, Yuehai Peng, Wenjing Song, Li Ren","doi":"10.1088/1758-5090/ade7b2","DOIUrl":"https://doi.org/10.1088/1758-5090/ade7b2","url":null,"abstract":"<p><p>Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In this study, we developed and optimized a series of gelatin methacrylate (GelMA)/collagen-based bioinks to fabricate convex corneal implants via 3D printing techniques. A novel method was proposed to enhance collagen solubility in neutral solutions by combining 2,3-epoxypropyltrimethylammonium chloride (EPTAC) with high-molecular-weight type I collagen, with simulations suggesting that the mechanism primarily involved electrostatic interactions. To evaluate whether keratocytes respond to a convex microenvironment and to verify the effectiveness of the proposed printing strategy for corneal stromal regeneration, particularly in mitigating corneal fibrosis, we fabricated topological structures of both flat and convex corneas. These structures were systematically analyzed for their influence on keratocyte-to-fibroblast transformation and keratocyte phenotype maintenance. Morphological observations, along with gene and protein expression analyses, demonstrated that the convex architecture provided an optimal microenvironment for preserving the keratocyte phenotype. Moreover, in vivo transplantation revealed the convex cornea effectively suppressed corneal fibrosis compared to the flat cornea. These findings suggest that convex cornea holds promise as a potential translational approach for treating corneal stroma regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A photosynthetic egg based oxygen-releasing platform to promote angiogenesis and tissue regeneration in diabetic wounds.","authors":"Yu He, Ying Zhao, Xingtang Niu, Ting Su, Chenlu Wu, Xinhui Wang, Yuan Ma, Xiaoqi Huang, Dan Sun, Feng Lu, Qiang Chang","doi":"10.1088/1758-5090/ade7b0","DOIUrl":"https://doi.org/10.1088/1758-5090/ade7b0","url":null,"abstract":"<p><p>Diabetic wounds represent a longstanding global health challenge attributable to tissue hypoxia resulting from impaired microcirculation, which impedes crucial physiological processes essential for wound healing, such as cell proliferation and migration. Oxygen-releasing biomaterials present a novel avenue for tissue reoxygenation therapy, offering advantages over conventional hyperbaric oxygen therapy (HBOT). Herein, we developed a microcosmic oxygen-releasing platform (MORP) named photosynthetic egg by utilizing egg white hydrogel with inherent bioactive factors for regenerative strength and electrostatic adsorbed Chlorella bringing photosynthetic oxygen production. The dissolved oxygen (DO) concentration leaped to more than 10 mg/L under hypoxic conditions through manipulating supplemental dosage and illumination intensity demonstrating high flexibility and controllability of MORP. In vitro experiments, coupled with transcriptome sequencing and qRT-PCR analysis, demonstrated that MORP significantly augmented cell proliferation, migration, and angiogenesis, serving as a rejuvenating agent to alleviate DNA damage and cellular dysfunction in hypoxic environments. Further in vivo investigations substantiated that MORP expedited diabetic wound healing by fostering tissue regeneration, collagen deposition, and angiogenesis owing to its bioactive constituents and reoxygenation capabilities. These findings underscore the potential therapeutic efficacy of MORP as an innovative approach for managing diabetic wounds.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in cell spheroid technology towards complex tissue formation guided by microfabrication and biomaterial innovations.","authors":"Rabi Ibrahim Saleh, Chaenyung Cha","doi":"10.1088/1758-5090/ade7b1","DOIUrl":"https://doi.org/10.1088/1758-5090/ade7b1","url":null,"abstract":"<p><p>Spheroids have become a de facto model three-dimensional (3D) tissue for studying various biological phenomena. While the technology to produce spheroids has become highly accessible and is routinely used by researchers, it has quite a long history, going through successive advances incorporating various scientific and engineering principles to acquire efficiency, accuracy, and high-throughput capability. More recently, the spheroid technology is advancing towards recapitulating complex physiological features, especially introducing extracellular components via biomaterials to more accurately portray tissue microenvironment. This review introduces and chronicles the advancement in spheroid technology in historical perspective, highlighting the key attributes of various techniques with notable examples. The spheroid technology is for convenience divided into three different generations, based on the era and the level of technological sophistication.&#xD.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteochondral organoid biofabrication: construction strategies, applications and perspectives.","authors":"Liwei Fu, Jiang Wu, Zhichao Zhang, Zhixing Zhang, Yazhe Zheng, Pinxue Li, Chuanyang Long, Xiang Sui, Shuyun Liu, Quanyi Guo","doi":"10.1088/1758-5090/ade740","DOIUrl":"https://doi.org/10.1088/1758-5090/ade740","url":null,"abstract":"<p><p>Osteochondral tissue is a functional complex with crosstalk shown to occur between cartilage and subchondral bone, playing a pivotal role in joint function and mobility. Osteochondral tissue repair has long been an enormous challenge in regenerative medicine and tissue engineering. With the development of biofabrication and biomaterials innovations, organoid technology, which can mimic the biological architecture and characteristics of organs through the construction of 3D tissue structures in vitro, provides novel insight into osteochondral tissue regeneration. This review explores the significance of osteochondral organoid biofabrication and the related biological structures and functions of the joint osteochondral unit. Furthermore, we summarize novel biofabrication technologies used for osteochondral organoids, such as 3D printing and microfluidics, and propose construction strategies for osteochondral organoids. Finally, the application directions and challenges of osteochondral organoids are outlined, emphasizing their potential for osteochondral disease treatment.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-destructive luminescence and PET imaging to monitor tissue microenvironment in microphysiological systems during brain metastasis using dissociated cerebral organoids.","authors":"Catherine Reed-McBain, Rithvik V Turaga, Seth R T Zima, Janmesh Patel, Anderson Weber Faletti Cunha, Jason Mixdorf, Lauren E Wehner, Jonathan W Engle, Reinier Hernandez, Stevens K Rehen, Helena L Borges, Jose M Ayuso","doi":"10.1088/1758-5090/ade1fb","DOIUrl":"10.1088/1758-5090/ade1fb","url":null,"abstract":"<p><p>During brain metastasis, tumor cells interact with the surrounding stroma, including neurons and astrocytes, to create a tumor-promoting microenvironment. However, the molecular and cellular factors driving tumor-neural stroma interactions remain unclear. Here, we developed a co-culture model of metastatic melanoma by combining metastatic melanoma cells with dissociated human iPSC-derived cerebral organoids, consisting of neurons and astrocytes, in a microfluidic device. We cultured these astrocytes and neurons in a 3D hydrogel that contained a domain with metastatic melanoma cells. This approach generated a spatially organized co-culture system with no physical boundary between the tumor and stromal compartments. Then, we leveraged several imaging modalities to study tumor-stroma interactions and changes in the microenvironment. Using non-destructive, luminescence-based methods, we spatially resolved changes in cell viability, metabolite concentration, and other biochemical parameters. We also used luminescence to analyze the effect of radionuclides on tumor cell viability and used PET imaging to monitor their diffusion across the system.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microgels: from synthesis to tissue regeneration applications.","authors":"Sung Yun Hann, Yunsung Kang, Haitao Cui, Lijie Grace Zhang","doi":"10.1088/1758-5090/addde9","DOIUrl":"10.1088/1758-5090/addde9","url":null,"abstract":"<p><p>Microgels have emerged as a versatile platform in tissue engineering and regenerative medicine, offering unique physicochemical properties, modularity, and the ability to mimic native extracellular matrix microenvironments. Derived from natural or synthetic hydrogels, microgels exhibit biocompatibility, controllability, and injectability, which make them suitable for diverse tissue engineering applications. This review systematically explores the fabrication methods of microgels and highlights their role in cell encapsulation, therapeutic delivery, and structural tissue development. Advanced strategies in microgel manufacturing, such as injectable hydrogels, assembled microgel platforms, and in-gel assemblies, have enabled the creation of highly customizable and functional tissue constructs. Additionally, three-dimensional bioprinting of microgels provides a high-throughput strategy to generate patient-specific scaffolds with precise spatial organization and enhanced cellular viability. It is expected that more efficient and cost-effective strategies for mass production and customization of microgel systems to specific cell types or patient needs are essential for future studies. The innovations, including stimuli-responsive and four-dimensional microgels, will expand their potential by enabling dynamic<i>in situ</i>tunable microenvironments. These advancements will enable optimal design, scalability, and integration into therapeutic applications, thereby accelerating the clinical translation of microgel-based therapies and driving the development of multifunctional tissue products.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formation of functionally robust human neocartilage from multiple donors using highly expanded costochondral cells.","authors":"Takumi Takahashi, Wendy E Brown, Cecilia T Trinh, Jerry C Hu, Kyriacos A Athanasiou","doi":"10.1088/1758-5090/ade18c","DOIUrl":"10.1088/1758-5090/ade18c","url":null,"abstract":"<p><p>Successful translation of allogeneic tissue-engineered neocartilage requires abundant functional cells. Human costal cartilage is a promising cell source, yet the effects of donor variability and extensive passaging remain unexplored. Therefore, this study investigated the functional (i.e. morphological, histological, mechanical, and biochemical) properties of hyaline-like neocartilage generated from high-passage human costochondral cells. A cell banking system was applied to seven donors to create master cell banks and subsequently working cell banks to fabricate P5 and P9 constructs using the processes of conservative chondrogenic passaging, aggregate rejuvenation, and self-assembly. Cell morphology or gene expression levels of these cells were correlated with mechanical and biochemical properties to identify predictive markers of neocartilage functional properties. Cells from younger donors (⩽3 months) expanded 8.7-fold more than cells from older donors (9-14 years). Cumulative expansion factors from P0 reached 3124-17397 at P5 and 1.4-36.2 million at P9. Aggregate rejuvenation was as effective at P9 as at P5 in restoring a hyaline cartilage-like phenotype, evidenced by increased cell circularity, upregulation of chondrogenic genes (e.g. >310-fold for<i>ACAN</i>; >200 000-fold for<i>COL2A1</i>; >2500-fold for<i>Chm-1</i>), and robust neocartilage functional properties. At P5, one young donor exhibited the highest functional properties (e.g. aggregate modulus = 310 kPa, Young's modulus = 2.9 MPa, GAG/ww = 9.5%, COL/ww = 3.1%). At P9, a different young donor had the highest functional properties (e.g. aggregate modulus = 220 kPa, Young's modulus = 2.3 MPa, GAG/ww = 8.6%, COL/ww = 3.4%). Gene expression levels after aggregate rejuvenation were identified to be predictive of neocartilage functional properties. For example,<i>ACAN, Chm-1</i>, and<i>MIA</i>positively correlated with Young's modulus, ultimate tensile strength (UTS), and GAG/dw, with<i>Chm-1</i>also correlating with shear modulus.<i>SOX9</i>correlated with Young's modulus and GAG/dw, while<i>MMP13</i>inversely correlated with UTS and GAG/dw. These findings support the translational potential of extensively passaged human costochondral cells, the need for donor screening, and the utility of gene expression markers to predict neocartilage functional properties.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}