Biofabrication最新文献

{"title":"Vascular dysfunction in hemorrhagic viral fevers: opportunities for organotypic modeling.","authors":"Evelyn Zarate-Sanchez, Steven C George, Monica L Moya, Claire Robertson","doi":"10.1088/1758-5090/ad4c0b","DOIUrl":"10.1088/1758-5090/ad4c0b","url":null,"abstract":"<p><p>The hemorrhagic fever viruses (HFVs) cause severe or fatal infections in humans. Named after their common symptom hemorrhage, these viruses induce significant vascular dysfunction by affecting endothelial cells, altering immunity, and disrupting the clotting system. Despite advances in treatments, such as cytokine blocking therapies, disease modifying treatment for this class of pathogen remains elusive. Improved understanding of the pathogenesis of these infections could provide new avenues to treatment. While animal models and traditional 2D cell cultures have contributed insight into the mechanisms by which these pathogens affect the vasculature, these models fall short in replicating<i>in vivo</i>human vascular dynamics. The emergence of microphysiological systems (MPSs) offers promising avenues for modeling these complex interactions. These MPS or 'organ-on-chip' models present opportunities to better mimic human vascular responses and thus aid in treatment development. In this review, we explore the impact of HFV on the vasculature by causing endothelial dysfunction, blood clotting irregularities, and immune dysregulation. We highlight how existing MPS have elucidated features of HFV pathogenesis as well as discuss existing knowledge gaps and the challenges in modeling these interactions using MPS. Understanding the intricate mechanisms of vascular dysfunction caused by HFV is crucial in developing therapies not only for these infections, but also for other vasculotropic conditions like sepsis.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silk fibroin increases the elasticity of alginate-gelatin hydrogels and regulates cardiac cell contractile function in cardiac bioinks.","authors":"L Vettori, H A Tran, H Mahmodi, E C Filipe, K Wyllie, C Liu Chung Ming, T R Cox, J Tipper, I V Kabakova, J Rnjak-Kovacina, C Gentile","doi":"10.1088/1758-5090/ad4f1b","DOIUrl":"10.1088/1758-5090/ad4f1b","url":null,"abstract":"<p><p>Silk fibroin (SF) is a natural protein extracted from<i>Bombyx mori</i>silkworm thread. From its common use in the textile industry, it emerged as a biomaterial with promising biochemical and mechanical properties for applications in the field of tissue engineering and regenerative medicine. In this study, we evaluate for the first time the effects of SF on cardiac bioink formulations containing cardiac spheroids (CSs). First, we evaluate if the SF addition plays a role in the structural and elastic properties of hydrogels containing alginate (Alg) and gelatin (Gel). Then, we test the printability and durability of bioprinted SF-containing hydrogels. Finally, we evaluate whether the addition of SF controls cell viability and function of CSs in Alg-Gel hydrogels. Our findings show that the addition of 1% (w/v) SF to Alg-Gel hydrogels makes them more elastic without affecting cell viability. However, fractional shortening (FS%) of CSs in SF-Alg-Gel hydrogels increases without affecting their contraction frequency, suggesting an improvement in contractile function in the 3D cultures. Altogether, our findings support a promising pathway to bioengineer bioinks containing SF for cardiac applications, with the ability to control mechanical and cellular features in cardiac bioinks.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079658","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 cell bank paradigm for preclinical evaluation of an analogous cellular product for an allogeneic cell therapy.","authors":"Rachel C Nordberg, Ryan P Donahue, M Gabriela Espinosa, Evelia Y Salinas, Jerry C Hu, Kyriacos A Athanasiou","doi":"10.1088/1758-5090/ad4de2","DOIUrl":"10.1088/1758-5090/ad4de2","url":null,"abstract":"<p><p>Toward the translation of allogeneic cell therapy products, cell banks are needed not only to manufacture the final human product but also during the preclinical evaluation of an animal-based analogous cellular product (ACP). These cell banks need to be established at both the master cell bank (MCB) level and the working cell bank (WCB) level. Inasmuch as most of the development of cell therapy products is at academic centers, it is imperative that academic researchers understand how to establish MCBs and WCBs within an academic environment. To illustrate this process, using articular cartilage as the model, a cell bank for an ACP was developed (MCBs at passage 2, WCBs at passage 5) to produce self-assembled neocartilage for preclinical evaluation (constructs at passage 7). The cell bank system is estimated to be able to produce between 160 000 and 400 000 constructs for each of the six MCBs. Overall, the ACP cell bank yielded constructs that are analogous to the intended human product, which is critical toward conducting preclinical evaluations of the ACP for inclusion in an Investigational New Drug application to the FDA.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maximization of uricase production in a column bioreactor through response surface methodology-based optimization.","authors":"Mohammad Hossein Taghizadeh, Khosro Khajeh, Niloofar Nasirpour, Seyyed Mohammad Mousavi","doi":"10.1088/1758-5090/ad467f","DOIUrl":"10.1088/1758-5090/ad467f","url":null,"abstract":"<p><p>Uricase (EC 1.7.3.3) is an oxidoreductase enzyme that is widely exploited for diagnostic and treatment purposes in medicine. This study focuses on producing recombinant uricase from<i>E. coli</i>BL21 in a bubble column bioreactor (BCB) and finding the optimal conditions for maximum uricase activity. The three most effective variables on uricase activity were selected through the Plackett-Burman design from eight different variables and were further optimized by the central composite design of the response surface methodology (RSM). The selected variables included the inoculum size (%v/v), isopropyl<i>β-d</i>-1-thiogalactopyranoside (IPTG) concentration (mM) and the initial pH of the culture medium. The activity of uricase, the final optical density at 600 nm wavelength (OD₆₀₀) and the final pH were considered as the responses of this optimization and were modeled. As a result, activity of 5.84 U·ml^-1and a final OD₆₀₀of 3.42 were obtained at optimum conditions of 3% v/v inoculum size, an IPTG concentration of 0.54 mM and a pH of 6.0. By purifying the obtained enzyme using a Ni-NTA agarose affinity chromatography column, 165 ± 1.5 mg uricase was obtained from a 600 ml cell culture. The results of this study show that BCBs can be a highly effective option for large-scale uricase production.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850680","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":"Pillar electrodes embedded in the skeletal muscle tissue for selective stimulation of biohybrid actuators with increased contractile distance.","authors":"Tingyu Li, Minghao Nie, Yuya Morimoto, Shoji Takeuchi","doi":"10.1088/1758-5090/ad4ba1","DOIUrl":"10.1088/1758-5090/ad4ba1","url":null,"abstract":"<p><p>Electrodes are crucial for controlling the movements of biohybrid robots, but their external placement outside muscle tissue often leads to inefficient and non-selective stimulation of nearby biohybrid actuators. To address this, we propose embedding pillar electrodes within the skeletal muscle tissue, resulting in enhanced contraction of the target muscle without affecting the neighbor tissue with a 4 mm distance. We use finite element method simulations to establish a selectivity model, correlating the VI_E(volume integration of electric field intensity within muscle tissue) with actual contractile distances under different amplitudes of electrical pulses. The simulated selective index closely aligns with experimental results, showing the potential of pillar electrodes for effective and selective biohybrid actuator stimulation. In experiments, we validated that the contractile distance and selectivity achieved with these pillar electrodes exceed conventional Au rod electrodes. This innovation has promising implications for building biohybrid robots with densely arranged muscle tissue, ultimately achieving more human-like movements. Additionally, our selectivity model offers valuable predictive tools for assessing electrical stimulation effects with different electrode designs.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921235","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":"Functionally graded hydrogels with opposing biochemical cues for osteochondral tissue engineering.","authors":"Aman Mahajan, Zahra Sifat Zaidi, Amit Shukla, Rakshita Saxena, Dhirendra S Katti","doi":"10.1088/1758-5090/ad467e","DOIUrl":"10.1088/1758-5090/ad467e","url":null,"abstract":"<p><p>Osteochondral tissue (OC) repair remains a significant challenge in the field of musculoskeletal tissue engineering. OC tissue displays a gradient structure characterized by variations in both cell types and extracellular matrix components, from cartilage to the subchondral bone. These functional gradients observed in the native tissue have been replicated to engineer OC tissue<i>in vitro</i>. While diverse fabrication methods have been employed to create these microenvironments, emulating the natural gradients and effective regeneration of the tissue continues to present a significant challenge. In this study, we present the design and development of CMC-silk interpenetrating (IPN) hydrogel with opposing dual biochemical gradients similar to native tissue with the aim to regenerate the complete OC unit. The gradients of biochemical cues were generated using an in-house-built extrusion system. Firstly, we fabricated a hydrogel that exhibits a smooth transition of sulfated carboxymethyl cellulose (sCMC) and TGF-<i>β</i>1 (SCT gradient hydrogel) from the upper to the lower region of the IPN hydrogel to regenerate the cartilage layer. Secondly, a hydrogel with a hydroxyapatite (HAp) gradient (HAp gradient hydrogel) from the lower to the upper region was fabricated to facilitate the regeneration of the subchondral bone layer. Subsequently, we developed a dual biochemical gradient hydrogel with a smooth transition of sCMC + TGF-<i>β</i>1 and HAp gradients in opposing directions, along with a blend of both biochemical cues in the middle. The results showed that the dual biochemical gradient hydrogels with biochemical cues corresponding to the three zones (i.e. cartilage, interface and bone) of the OC tissue led to differentiation of bone-marrow-derived mesenchymal stem cells to zone-specific lineages, thereby demonstrating their efficacy in directing the fate of progenitor cells. In summary, our study provided a simple and innovative method for incorporating gradients of biochemical cues into hydrogels. The gradients of biochemical cues spatially guided the differentiation of stem cells and facilitated tissue growth, which would eventually lead to the regeneration of the entire OC tissue with a smooth transition from cartilage (soft) to bone (hard) tissues. This promising approach is translatable and has the potential to generate numerous biochemical and biophysical gradients for regeneration of other interface tissues, such as tendon-to-muscle and ligament-to-bone.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851320","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":"hiPSC-derived macrophages improve drug sensitivity and selectivity in a macrophage-incorporating organoid culture model.","authors":"Seongyea Jo, Sung Bum Park, Hyemin Kim, Ilkyun Im, Haneul Noh, Eun-Mi Kim, Ki Young Kim, Michael Oelgeschläger, Jong-Hoon Kim, Han-Jin Park","doi":"10.1088/1758-5090/ad4c0a","DOIUrl":"10.1088/1758-5090/ad4c0a","url":null,"abstract":"<p><p>Accurate simulation of different cell type interactions is crucial for physiological and precise<i>in vitro</i>drug testing. Human tissue-resident macrophages are critical for modulating disease conditions and drug-induced injuries in various tissues; however, their limited availability has hindered their use in<i>in vitro</i>modeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating human-induced pluripotent stem cell (hiPSC)-derived pre-macrophages into organoid and scaffold cell models. The fully differentiated cells in these organoids exhibited functional characteristics of tissue-resident macrophages with enriched pan-macrophage markers and the potential for M1/M2 subtype specialization upon cytokine stimulation. In a hepatic organoid model, the integrated macrophages replicated typical intrinsic properties, including cytokine release, polarization, and phagocytosis, and the co-culture model was more responsive to drug-induced liver injury than a macrophage-free model. Furthermore, alveolar organoid models containing these hiPSC-derived macrophages also showed increased drug and chemical sensitivity to pulmonary toxicants. Moreover, 3D adipocyte scaffold models incorporating macrophages effectively simulated in vivo insulin resistance observed in adipose tissue and showed improved insulin sensitivity on exposure to anti-diabetic drugs. Overall, the findings demonstrated that incorporating hiPSC-derived macrophages into organoid culture models resulted in more physiological and sensitive<i>in vitro</i>drug evaluation and screening systems.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943839","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":"Basic models to advanced systems: harnessing the power of organoids-based microphysiological models of the human brain.","authors":"Katherine Boylin, Grace V Aquino, Michael Purdon, Kimia Abedi, Magdalena Kasendra, Riccardo Barrile","doi":"10.1088/1758-5090/ad4c08","DOIUrl":"10.1088/1758-5090/ad4c08","url":null,"abstract":"<p><p>Understanding the complexities of the human brain's function in health and disease is a formidable challenge in neuroscience. While traditional models like animals offer valuable insights, they often fall short in accurately mirroring human biology and drug responses. Moreover, recent legislation has underscored the need for more predictive models that more accurately represent human physiology. To address this requirement, human-derived cell cultures have emerged as a crucial alternative for biomedical research. However, traditional static cell culture models lack the dynamic tissue microenvironment that governs human tissue function. Advanced<i>in vitro</i>systems, such as organoids and microphysiological systems (MPSs), bridge this gap by offering more accurate representations of human biology. Organoids, which are three-dimensional miniaturized organ-like structures derived from stem cells, exhibit physiological responses akin to native tissues, but lack essential tissue-specific components such as functional vascular structures and immune cells. Recent endeavors have focused on incorporating endothelial cells and immune cells into organoids to enhance vascularization, maturation, and disease modeling. MPS, including organ-on-chip technologies, integrate diverse cell types and vascularization under dynamic culture conditions, revolutionizing brain research by bridging the gap between<i>in vitro</i>and<i>in vivo</i>models. In this review, we delve into the evolution of MPS, with a particular focus on highlighting the significance of vascularization in enhancing the viability, functionality, and disease modeling potential of organoids. By examining the interplay of vasculature and neuronal cells within organoids, we can uncover novel therapeutic targets and gain valuable insights into disease mechanisms, offering the promise of significant advancements in neuroscience and improved patient outcomes.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943837","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":"Biofabrication of 3D adipose tissue via assembly of composite stem cell spheroids containing adipo-inductive dual-signal delivery nanofibers.","authors":"Sangmin Lee, Jeongbok Lee, Soomi Choi, Eunhyung Kim, Hyunseok Kwon, Jinkyu Lee, Sung Min Kim, Heungsoo Shin","doi":"10.1088/1758-5090/ad4a67","DOIUrl":"10.1088/1758-5090/ad4a67","url":null,"abstract":"<p><p>Reconstruction of large 3D tissues based on assembly of micro-sized multi-cellular spheroids has gained attention in tissue engineering. However, formation of 3D adipose tissue from spheroids has been challenging due to the limited adhesion capability and restricted cell mobility of adipocytes in culture media. In this study, we addressed this problem by developing adipo-inductive nanofibers enabling dual delivery of indomethacin and insulin. These nanofibers were introduced into composite spheroids comprising human adipose-derived stem cells (hADSCs). This approach led to a significant enhancement in the formation of uniform lipid droplets, as evidenced by the significantly increased Oil red O-stained area in spheroids incorporating indomethacin and insulin dual delivery nanofibers (56.9 ± 4.6%) compared to the control (15.6 ± 3.5%) with significantly greater gene expression associated with adipogenesis (<i>C/EBPA, PPARG, FABP4</i>, and adiponectin) of hADSCs. Furthermore, we investigated the influence of culture media on the migration and merging of spheroids and observed significant decrease in migration and merging of spheroids in adipogenic differentiation media. Conversely, the presence of adipo-inductive nanofibers promoted spheroid fusion, allowing the formation of macroscopic 3D adipose tissue in the absence of adipogenic supplements while facilitating homogeneous adipogenesis of hADSCs. The approach described here holds promise for the generation of 3D adipose tissue constructs by scaffold-free assembly of stem cell spheroids with potential applications in clinical and organ models.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910839","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":"Droplet bioprinting of acellular and cell-laden structures at high-resolutions.","authors":"Puskal Kunwar, Ujjwal Aryal, Arun Poudel, Daniel Fougnier, Zachary J Geffert, Rui Xie, Zhen Li, Pranav Soman","doi":"10.1088/1758-5090/ad4c09","DOIUrl":"10.1088/1758-5090/ad4c09","url":null,"abstract":"<p><p>Advances in digital light projection(DLP) based (bio) printers have made printing of intricate structures at high resolution possible using a wide range of photosensitive bioinks. A typical setup of a DLP bioprinter includes a vat or reservoir filled with liquid bioink, which presents challenges in terms of cost associated with bioink synthesis, high waste, and gravity-induced cell settling, contaminations, or variation in bioink viscosity during the printing process. Here, we report a vat-free, low-volume, waste-free droplet bioprinting method capable of rapidly printing 3D soft structures at high resolution using model bioinks and model cells. A multiphase many-body dissipative particle dynamics model was developed to simulate the dynamic process of droplet-based DLP printing and elucidate the roles of surface wettability and bioink viscosity. Process variables such as light intensity, photo-initiator concentration, and bioink formulations were optimized to print 3D soft structures (∼0.4-3 kPa) with a typical layer thickness of 50<i>µ</i>m, an XY resolution of 38 ± 1.5<i>μ</i>m and Z resolution of 237 ± 5.4<i>µ</i>m. To demonstrate its versatility, droplet bioprinting was used to print a range of acellular 3D structures such as a lattice cube, a Mayan pyramid, a heart-shaped structure, and a microfluidic chip with endothelialized channels. Droplet bioprinting, performed using model C3H/10T1/2 cells, exhibited high viability (90%) and cell spreading. Additionally, microfluidic devices with internal channel networks lined with endothelial cells showed robust monolayer formation while osteoblast-laden constructs showed mineral deposition upon osteogenic induction. Overall, droplet bioprinting could be a low-cost, no-waste, easy-to-use, method to make customized bioprinted constructs for a range of biomedical applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943838","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}