BiofabricationPub Date : 2024-11-04DOI: 10.1088/1758-5090/ad8e87
Şule Arıcı, Ali Kamali, Duygu Ege
{"title":"CMC/Gel/GO 3D-printed cardiac patches: GO and CMC improve flexibility and promote H9C2 cell proliferation, while EDC/NHS enhances stability.","authors":"Şule Arıcı, Ali Kamali, Duygu Ege","doi":"10.1088/1758-5090/ad8e87","DOIUrl":"https://doi.org/10.1088/1758-5090/ad8e87","url":null,"abstract":"<p><p>In this research, carboxymethyl cellulose (CMC)/gelatin (Gel)/graphene oxide (GO)-based scaffolds were produced by using extrusion-based 3D printing for cardiac tissue regeneration. Rheological studies were conducted to evaluate the printability of CMC/Gel/GO inks, which revealed that CMC increased viscosity and enhanced printability. The 3D-printed cardiac patches were crosslinked with N-(3-dimethylaminopropyl)-n'-ethylcarbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) (100:20 mM, 50:10 mM, 25:5 mM) and then characterized by mechanical analysis, electrical conductivity testing, contact angle measurements and degradation studies. Subsequently, cell culture studies were conducted to evaluate the viability of H9C2 cardiomyoblast cells by using the Alamar Blue assay and fluorescence imaging. A high concentration of EDC/NHS (100:20 mM) led to the stability of the patches; however, it drastically reduced the flexibility of the scaffolds. Conversely, a concentration of 25:5 mM resulted in flexible but unstable scaffolds in PBS solution. The suitable EDC/NHS concentration was found to be 50:10 mM, as it produced flexible, stable, and stiff cardiac scaffolds with high ultimate tensile strength (UTS). Mechanical characterization revealed that % the strain at break of C15/G7.5/GO1 exhibited a remarkable increase of 61.03% compared to C15/G7.5 samples. The improvement of flexibility was attributed to the hydrogen bonding between CMC, Gel and GO. The electrical conductivity of 3D printed CMC/Gel/GO cardiac patches was 7.0×10-3 S/cm, demonstrating suitability for mimicking the desired electrical conductivity of human myocardium. The incorporation of 1 wt% of GO and addition of CMC concentration from 7.5 wt % to 15 wt % significantly enhanced relative % cell viability. Overall, although this research is at its infancy, CMC/Gel/GO cardiac patches have potential to improve the physiological function of cardiac tissue.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575335","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}
BiofabricationPub Date : 2024-11-04DOI: 10.1088/1758-5090/ad8b70
Nihan Sengokmen-Ozsoz, Mina Aleemardani, Marco Palanca, Alice Hann, Gwendolen C Reilly, Enrico Dall'Ara, Frederik Claeyssens
{"title":"Fabrication of hierarchically porous trabecular bone replicas via 3D printing with high internal phase emulsions (HIPEs).","authors":"Nihan Sengokmen-Ozsoz, Mina Aleemardani, Marco Palanca, Alice Hann, Gwendolen C Reilly, Enrico Dall'Ara, Frederik Claeyssens","doi":"10.1088/1758-5090/ad8b70","DOIUrl":"10.1088/1758-5090/ad8b70","url":null,"abstract":"<p><p>Combining emulsion templating with additive manufacturing enables the production of inherently porous scaffolds with multiscale porosity. This approach incorporates interconnected porous materials, providing a structure that supports cell ingrowth. However, 3D printing hierarchical porous structures that combine semi-micropores and micropores remains a challenging task. Previous studies have demonstrated that using a carefully adjusted combination of light absorbers and photoinitiators in the resin can produce open surface porosity, sponge-like internal structures, and a printing resolution of about 150<i>µ</i>m. In this study, we explored how varying concentrations of tartrazine (0, 0.02, 0.04, and 0.08 wt%) as a light absorber affect the porous structure of acrylate-based polymerized medium internal phase emulsions fabricated via vat photopolymerization. Given the importance of a porous and interconnected structure for tissue engineering and regenerative medicine, we tested cell behavior on these 3D-printed disk samples using MG-63 cells, examining metabolic activity, adhesion, and morphology. The 0.08 wt% tartrazine-containing 3D-printed sample (008 T) demonstrated the best cell proliferation and adhesion. To show that this high internal phase emulsion (HIPE) resin can be used to create complex structures for biomedical applications, we 3D-printed trabecular bone structures based on microCT imaging. These structures were further evaluated for cell behavior and migration, followed by microCT analysis after 60 days of cell culture. This research demonstrates that HIPEs can be used as a resin to print trabecular bone mimics using additive manufacturing, which could be further developed for lab-on-a-chip models of healthy and diseased bone.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494585","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}
BiofabricationPub Date : 2024-11-01DOI: 10.1088/1758-5090/ad8965
Yangwang Jin, Ming Yang, Weixin Zhao, Meng Liu, Wenzhuo Fang, Yuhui Wang, Guo Gao, Ying Wang, Qiang Fu
{"title":"Scaffold-based tissue engineering strategies for urethral repair and reconstruction.","authors":"Yangwang Jin, Ming Yang, Weixin Zhao, Meng Liu, Wenzhuo Fang, Yuhui Wang, Guo Gao, Ying Wang, Qiang Fu","doi":"10.1088/1758-5090/ad8965","DOIUrl":"10.1088/1758-5090/ad8965","url":null,"abstract":"<p><p>Urethral strictures are common in urology; however, the reconstruction of long urethral strictures remains challenging. There are still unavoidable limitations in the clinical application of grafts for urethral injuries, which has facilitated the advancement of urethral tissue engineering. Tissue-engineered urethral scaffolds that combine cells or bioactive factors with a biomaterial to mimic the native microenvironment of the urethra, offer a promising approach to urethral reconstruction. Despite the recent rapid development of tissue engineering materials and techniques, a consensus on the optimal strategy for urethral repair and reconstruction is still lacking. This review aims to collect the achievements of urethral tissue engineering in recent years and to categorize and summarize them to shed new light on their design. Finally, we visualize several important future directions for urethral repair and reconstruction.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457142","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}
BiofabricationPub Date : 2024-10-30DOI: 10.1088/1758-5090/ad88a7
Yusuf Mastoor, Mahsa Karimi, Michael Sun, Fereshteh Ahadi, Pattie Mathieu, Mingyue Fan, Lin Han, Li-Hsin Han, Alisa Morss Clyne
{"title":"Vascular smooth muscle cells can be circumferentially aligned inside a channel using tunable gelatin microribbons.","authors":"Yusuf Mastoor, Mahsa Karimi, Michael Sun, Fereshteh Ahadi, Pattie Mathieu, Mingyue Fan, Lin Han, Li-Hsin Han, Alisa Morss Clyne","doi":"10.1088/1758-5090/ad88a7","DOIUrl":"10.1088/1758-5090/ad88a7","url":null,"abstract":"<p><p>The gold standard to measure arterial health is vasodilation in response to nitric oxide. Vasodilation is generally measured via pressure myography of arteries isolated from animal models. However, animal arteries can be difficult to obtain and may have limited relevance to human physiology. It is, therefore, critical to engineer human cell-based arterial models capable of contraction. Vascular smooth muscle cells (SMCs) must be circumferentially aligned around the vessel lumen to contract the vessel, which is challenging to achieve in a soft blood vessel model. In this study, we used gelatin microribbons to circumferentially align SMCs inside a hydrogel channel. To accomplish this, we created tunable gelatin microribbons of varying stiffnesses and thicknesses and assessed how SMCs aligned along them. We then wrapped soft, thick microribbons around a needle and encapsulated them in a gelatin methacryloyl hydrogel, forming a microribbon-lined channel. Finally, we seeded SMCs inside the channel and showed that they adhered best to fibronectin and circumferentially aligned in response to the microribbons. Together, these data show that tunable gelatin microribbons can be used to circumferentially align SMCs inside a channel. This technique can be used to create a human artery-on-a-chip to assess vasodilation via pressure myography, as well as to align other cell types for 3D<i>in vitro</i>models.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457233","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}
BiofabricationPub Date : 2024-10-24DOI: 10.1088/1758-5090/ad8379
S R Moxon, Z McMurran, M J Kibble, M Domingos, J E Gough, S M Richardson
{"title":"3D bioprinting of an intervertebral disc tissue analogue with a highly aligned annulus fibrosus via suspended layer additive manufacture.","authors":"S R Moxon, Z McMurran, M J Kibble, M Domingos, J E Gough, S M Richardson","doi":"10.1088/1758-5090/ad8379","DOIUrl":"10.1088/1758-5090/ad8379","url":null,"abstract":"<p><p>Intervertebral disc (IVD) function is achieved through integration of its two component regions: the nucleus pulposus (NP) and the annulus fibrosus (AF). The NP is soft (0.3-5 kPa), gelatinous and populated by spherical NP cells in a polysaccharide-rich extracellular matrix (ECM). The AF is much stiffer (∼100 kPa) and contains layers of elongated AF cells in an aligned, fibrous ECM. Degeneration of the disc is a common problem with age being a major risk factor. Progression of IVD degeneration leads to chronic pain and can result in permanent disability. The development of therapeutic solutions for IVD degeneration is impaired by a lack of<i>in vitro</i>models of the disc that are capable of replicating the fundamental structure and biology of the tissue. This study aims to investigate if a newly developed suspended hydrogel bioprinting system (termed SLAM) could be employed to fabricate IVD analogues with integrated structural and compositional features similar to native tissue. Bioprinted IVD analogues were fabricated to recapitulate structural, morphological and biological components present in the native tissue. The constructs replicated key structural components of native tissue with the presence of a central, polysaccharide-rich NP surrounded by organised, aligned collagen fibres in the AF. Cell tracking, actin and matrix staining demonstrated that embedded NP and AF cells exhibited morphologies and phenotypes analogous to what is observed<i>in vivo</i>with elongated, aligned AF cells and spherical NP cells that deposited HA into the surrounding environment. Critically, it was also observed that the NP and AF regions contained a defined cellular and material interface and segregated regions of the two cell types, thus mimicking the highly regulated structure of the IVD.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375046","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":"Calcium phosphate complex of recombinant human thrombomodulin promote bone formation in interbody fusion.","authors":"Cheng-Li Lin, Yu-Wei Chen, Cheng-Hsiang Kuo, Ting-Yuan Tu, Hua-Lin Wu, Jui-Chen Tsai, Yan-Jye Shyong","doi":"10.1088/1758-5090/ad8035","DOIUrl":"10.1088/1758-5090/ad8035","url":null,"abstract":"<p><p>Interbody fusion is an orthopedic surgical procedure to connect two adjacent vertebrae in patients suffering from spinal disc disease. The combination of synthetic bone grafts with protein-based drugs is an intriguing approach to stimulate interbody bone growth, specifically in patients exhibiting restricted bone progression. Recombinant human thrombomodulin (rhTM), a novel protein drug characterized by its superior stability and potency, shows promise in enhancing bone formation. A composite bone graft, termed CaP-rhTM, has been synthesized, combining calcium phosphate (CaP) microparticles as a delivery vehicle for rhTM to facilitate interbody fusion.<i>In vitro</i>studies have demonstrated that rhTM significantly promotes the proliferation and maturation of preosteoblasts at nanogram dosage, while exerting minimal impact on osteosarcoma cell growth. The expression levels of mature osteoblast markers, including osteocalcin, osteopontin, alkaline phosphatase, and calcium deposition were also enhanced by rhTM. In rat caudal disc model of interbody fusion, CaP-rhTM with 800 ng of drug dosage was implanted along with a polylactic acid cage, to ensure structural stability within the intervertebral space. Microcomputed tomography analyses revealed that from 8 to 24 weeks, CaP-rhTM substantially improves both bone volume and trabecular architecture, in addition to the textural integrity of bony endplate surfaces. Histological examination confirmed the formation of a continuous bone bridge connecting adjacent vertebrae. Furthermore, biomechanical assessment via three-point bending tests indicated an improved bone quality of the fused disc. This study has demostrated that rhTM exhibits considerable potential in promoting osteogenesis. The use of CaP-rhTM has also shown significant improvements in promoting interbody fusion.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341030","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}
BiofabricationPub Date : 2024-10-24DOI: 10.1088/1758-5090/ad837a
Jessica T Y Cheng, Edwin C K Tan, Lifeng Kang
{"title":"Pharmacy 3D printing.","authors":"Jessica T Y Cheng, Edwin C K Tan, Lifeng Kang","doi":"10.1088/1758-5090/ad837a","DOIUrl":"10.1088/1758-5090/ad837a","url":null,"abstract":"<p><p>A significant limitation of the 'one size fits all' medication approach is the lack of consideration for special population groups. 3D printing technology has revolutionised the landscape of pharmaceuticals and pharmacy practice, playing an integral role in enabling on-demand production of customised medication. Compared to traditional pharmaceutical processes, 3D printing has major advantages in producing tailored dosage forms with unique drug release mechanisms. Moreover, this technology has enabled the combination of multiple drugs in a single formulation addressing key issues of medication burden. Development of 3D printing in pharmacy applications and large-scale pharmaceutical manufacturing has substantially increased in recent years. This review focuses on the emergence of extrusion-based 3D printing, particularly semi solid extrusion, fused deposition modelling and direct powder extrusion, which are currently the most commonly studied for pharmacy practice. The concept of each technique is summarised, with examples of current and potential applications. Next, recent advancements in the 3D printer market and pharmacist perceptions are discussed. Finally, the benefits, challenges and prospects of pharmacy 3D printing technology are highlighted, emphasising its significance in changing the future of this field.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375047","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}
BiofabricationPub Date : 2024-10-24DOI: 10.1088/1758-5090/ad80ce
Brian J Kwee, Mona Mansouri, Adovi Akue, Kyung E Sung
{"title":"On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking.","authors":"Brian J Kwee, Mona Mansouri, Adovi Akue, Kyung E Sung","doi":"10.1088/1758-5090/ad80ce","DOIUrl":"10.1088/1758-5090/ad80ce","url":null,"abstract":"<p><p>The lymph node paracortex, also known as the T-cell zone, consists of a network of fibroblastic reticular cells (FRCs) that secrete chemokines to induce T-cell and dendritic cell (DC) trafficking into the paracortex. To model the lymph node paracortex, we utilize multi-channel microfluidic devices to engineer a 3D lymph node stromal network from human cultured FRCs embedded in a collagen I-fibrin hydrogel. In the hydrogel, the FRCs self-assemble into an interconnected network, secrete the extracellular matrix proteins entactin, collagen IV, and fibronectin, as well as express an array of immune cell trafficking chemokines. Although the engineered FRC network did not secrete characteristic CCR7-ligand chemokines (i.e. CCL19 and CCL21), human primary TNF-<i>α</i>matured monocyte-derived DCs, CD45RA<sup>+</sup>T-cells, and CD45RA<sup>-</sup>T-cells migrate toward the lymph node stromal network to a greater extent than toward a blank hydrogel. Furthermore, the FRCs co-recruit DCs and antigen-specific T-cells into the lymph node stromal network. This engineered lymph node stromal network may help evaluate how human DCs and T-cells migrate into the lymph node paracortex via CCR7-independent mechanisms.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341031","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}
BiofabricationPub Date : 2024-10-24DOI: 10.1088/1758-5090/ad818a
Flavio Bonanini, Roelof Dinkelberg, Manuel Caro Torregrosa, Nienke Kortekaas, Tessa M S Hagens, Stéphane Treillard, Dorota Kurek, Vincent van Duinen, Paul Vulto, Kristin Bircsak
{"title":"A microvascularized<i>in vitro</i>liver model for disease modeling and drug discovery.","authors":"Flavio Bonanini, Roelof Dinkelberg, Manuel Caro Torregrosa, Nienke Kortekaas, Tessa M S Hagens, Stéphane Treillard, Dorota Kurek, Vincent van Duinen, Paul Vulto, Kristin Bircsak","doi":"10.1088/1758-5090/ad818a","DOIUrl":"10.1088/1758-5090/ad818a","url":null,"abstract":"<p><p>Drug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects of liver (patho)-physiology is likely contributing to the inefficiency of developing effective treatments. Of particular notice is the common omission of an organized microvascular component despite its importance in maintaining liver function and its involvement in the development of several pathologies. Increasing the complexity of<i>in vitro</i>models is usually associated with a lack of scalability and robustness which hinders their implementation in drug development pipelines. Here, we describe a comprehensive liver microphysiological system comprising stellates, liver-derived endothelial cells and hepatocytes conceived within a scalable and automated platform. We show that endothelial cells self-organize in a microvascular network when co-cultured with stellates in a hydrogel. In a tri-culture, hepatocytes polarize accordingly, with a basolateral side facing blood vessels and an apical side facing bile-canaliculi-like structures. Stellates interact and surround the hollow microvessels. Steatosis was induced by exogenous administration of fatty acids which could be prevented by co-administration of firsocostat. Administration of TGF-<i>β</i>resulted in an activated stellate cells phenotype which could be prevented by the co-administration of SB-431542. The model was implemented on a microtiter plate format comprising 64 chips which enabled the development of a fully automated, multiplexed fibrosis assay with a robust Z' factor suitable for high-throughput applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341028","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}
BiofabricationPub Date : 2024-10-24DOI: 10.1088/1758-5090/ad7f8f
Nashaita Y Patrawalla, Karly Liebendorfer, Vipuil Kishore
{"title":"An innovative 4D printing approach for fabrication of anisotropic collagen scaffolds.","authors":"Nashaita Y Patrawalla, Karly Liebendorfer, Vipuil Kishore","doi":"10.1088/1758-5090/ad7f8f","DOIUrl":"10.1088/1758-5090/ad7f8f","url":null,"abstract":"<p><p>Collagen anisotropy is known to provide the essential topographical cues to guide tissue-specific cell function. Recent work has shown that extrusion-based printing using collagenous inks yield 3D scaffolds with high geometric precision and print fidelity. However, these scaffolds lack collagen anisotropy. In this study, extrusion-based 3D printing was combined with a magnetic alignment approach in an innovative 4D printing scheme to generate 3D collagen scaffolds with high degree of collagen anisotropy. Specifically, the 4D printing process parameters-collagen (Col):xanthan gum (XG) ratio (Col:XG; 1:1, 4:1, 9:1 v/v), streptavidin-coated magnetic particle concentration (SMP; 0, 0.2, 0.4 mg ml<sup>-1</sup>), and print flow speed (2, 3 mm s<sup>-1</sup>)-were modulated and the effects of these parameters on rheological properties, print fidelity, and collagen alignment were assessed. Further, the effects of collagen anisotropy on human mesenchymal stem cell (hMSC) morphology, orientation, metabolic activity, and ligamentous differentiation were investigated. Results showed that increasing the XG composition (Col:XG 1:1) enhanced ink viscosity and yielded scaffolds with good print fidelity but poor collagen alignment. On the other hand, use of inks with lower XG composition (Col:XG 4:1 and 9:1) together with 0.4 mg ml<sup>-1</sup>SMP concentration yielded scaffolds with high degree of collagen alignment albeit with suboptimal print fidelity. Modulating the print flow speed conditions (2 mm s<sup>-1</sup>) with 4:1 Col:XG inks and 0.4 mg ml<sup>-1</sup>SMP resulted in improved print fidelity of the collagen scaffolds while retaining high level of collagen anisotropy. Cell studies revealed hMSCs orient uniformly on aligned collagen scaffolds. More importantly, collagen anisotropy was found to trigger tendon or ligament-like differentiation of hMSCs. Together, these results suggest that 4D printing is a viable strategy to generate anisotropic collagen scaffolds with significant potential for use in tendon and ligament tissue engineering applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142341029","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}