Pub Date : 2025-11-12DOI: 10.1016/j.bprint.2025.e00454
Amit Kumar Das , Akramul Ansary , Bhargab Jyoti Sahariah , Nilutpal Sharma Bora
Pharmaceutical excipients have undergone a paradigm shift from traditionally inert formulation components to advanced functional materials that play critical roles in drug delivery, stability, manufacturability, and therapeutic efficacy. This review explores the transformation of excipients in the context of modern pharmaceutical manufacturing, with particular emphasis on their integration into additive manufacturing technologies such as 3D printing. Novel excipients—including smart polymers, co-processed materials, bioinspired nanostructures, and environmentally sustainable agents—have demonstrated enhanced rheological, thermal, and structural properties necessary for layer-by-layer drug fabrication. These advancements support the development of complex dosage forms, personalized medicines, and controlled-release systems that cannot be achieved through conventional manufacturing. Additionally, regulatory and analytical challenges associated with novel excipients are discussed, highlighting the need for global harmonization and advanced validation methods. As pharmaceutical manufacturing continues to embrace digital and precision-driven technologies, the strategic design and application of next-generation excipients will be central to enabling scalable, safe, and patient-centric drug delivery systems.
{"title":"Pharmaceutical excipients: Metamorphosis from conventional formulation to 3D printing","authors":"Amit Kumar Das , Akramul Ansary , Bhargab Jyoti Sahariah , Nilutpal Sharma Bora","doi":"10.1016/j.bprint.2025.e00454","DOIUrl":"10.1016/j.bprint.2025.e00454","url":null,"abstract":"<div><div>Pharmaceutical excipients have undergone a paradigm shift from traditionally inert formulation components to advanced functional materials that play critical roles in drug delivery, stability, manufacturability, and therapeutic efficacy. This review explores the transformation of excipients in the context of modern pharmaceutical manufacturing, with particular emphasis on their integration into additive manufacturing technologies such as 3D printing. Novel excipients—including smart polymers, co-processed materials, bioinspired nanostructures, and environmentally sustainable agents—have demonstrated enhanced rheological, thermal, and structural properties necessary for layer-by-layer drug fabrication. These advancements support the development of complex dosage forms, personalized medicines, and controlled-release systems that cannot be achieved through conventional manufacturing. Additionally, regulatory and analytical challenges associated with novel excipients are discussed, highlighting the need for global harmonization and advanced validation methods. As pharmaceutical manufacturing continues to embrace digital and precision-driven technologies, the strategic design and application of next-generation excipients will be central to enabling scalable, safe, and patient-centric drug delivery systems.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00454"},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.bprint.2025.e00452
Kristin Schüler , Ahed Almalla , Sebastian Seitel , Friederike Ebner , Sebastian Seiffert , Marie Weinhart , Laura Elomaa
Formation of blood vessels sustaining the metabolic demands of the tissue-forming cells remains the greatest challenge in engineered tissues for regenerative medicine and in vitro organ modelling. We investigated vascularization of covalently crosslinked hydrogels derived from porcine decellularized small intestinal submucosa (dSIS), focusing on optimizing conditions for bioprinting and subsequent vascular network formation. dSIS was solubilized via enzymatic digestion with papain and formulated into a photocrosslinkable bioresin by combining it with a photoinitiator system of ruthenium/sodium persulfate (Ru/SPS) and human umbilical vein endothelial cells (HUVECs). This bioresin allowed bioprinting of cell-laden dSIS hydrogels via vat photopolymerization. Cytotoxicity testing of the bioresins revealed high viability of HUVECs encapsulated in the dSIS hydrogels, and coculturing the bioprinted HUVEC-laden hydrogels in presence of human dermal fibroblasts resulted in the formation of an interconnected vascular network within the gels. A lower Ru/SPS concentration (0.25/5 mM) in the bioresin led to the formation of a denser vascular network compared to the higher one (0.5/5 mM), indicating the significance of the Ru/SPS concentration in the covalent hydrogel crosslinking and the subsequent vascularization. The lowest dSIS concentration (0.375 wt-%) yielded soft hydrogels with incomplete printing fidelity, while the stiffest (0.75 wt-%) hydrogels failed to support the HUVEC network formation. The dSIS concentration of 0.5 wt-% was found optimal for both the bioprinting fidelity and the vascular network formation. Our findings highlighted the need for optimizing hydrogel composition and thus its covalent crosslinking for efficient vascularization of bioprinted tissue constructs, with potential implications for further development of vascularized 3D tissue models.
{"title":"Engineering in vitro vascularization: Enhanced network formation in bioprinted, vat photopolymerized dECM constructs","authors":"Kristin Schüler , Ahed Almalla , Sebastian Seitel , Friederike Ebner , Sebastian Seiffert , Marie Weinhart , Laura Elomaa","doi":"10.1016/j.bprint.2025.e00452","DOIUrl":"10.1016/j.bprint.2025.e00452","url":null,"abstract":"<div><div>Formation of blood vessels sustaining the metabolic demands of the tissue-forming cells remains the greatest challenge in engineered tissues for regenerative medicine and <em>in vitro</em> organ modelling. We investigated vascularization of covalently crosslinked hydrogels derived from porcine decellularized small intestinal submucosa (dSIS), focusing on optimizing conditions for bioprinting and subsequent vascular network formation. dSIS was solubilized via enzymatic digestion with papain and formulated into a photocrosslinkable bioresin by combining it with a photoinitiator system of ruthenium/sodium persulfate (Ru/SPS) and human umbilical vein endothelial cells (HUVECs). This bioresin allowed bioprinting of cell-laden dSIS hydrogels via vat photopolymerization. Cytotoxicity testing of the bioresins revealed high viability of HUVECs encapsulated in the dSIS hydrogels, and coculturing the bioprinted HUVEC-laden hydrogels in presence of human dermal fibroblasts resulted in the formation of an interconnected vascular network within the gels. A lower Ru/SPS concentration (0.25/5 mM) in the bioresin led to the formation of a denser vascular network compared to the higher one (0.5/5 mM), indicating the significance of the Ru/SPS concentration in the covalent hydrogel crosslinking and the subsequent vascularization. The lowest dSIS concentration (0.375 wt-%) yielded soft hydrogels with incomplete printing fidelity, while the stiffest (0.75 wt-%) hydrogels failed to support the HUVEC network formation. The dSIS concentration of 0.5 wt-% was found optimal for both the bioprinting fidelity and the vascular network formation. Our findings highlighted the need for optimizing hydrogel composition and thus its covalent crosslinking for efficient vascularization of bioprinted tissue constructs, with potential implications for further development of vascularized 3D tissue models.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00452"},"PeriodicalIF":0.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.bprint.2025.e00453
Francisco Javier Flores-Loera , Ariel Cantoral-Sánchez , Luis Fernando Carmona-Ramirez , Ilsa Pamela de los Santos-Hernández , Saulo Montaño-Medina , David Cantú-Fernández , Esther Pérez-Carrillo , José Rodríguez-Rodríguez , Claudia Maribel Luna-Aguirre , Francisco Javier Sierra-Valdez , Grissel Trujillo-de Santiago , Mario Moisés Alvarez
Probiotic therapies offer great potential for addressing gut dysbiosis, but current approaches are limited by low strain diversity, high production costs, and the challenges of culturing strict anaerobes. To overcome these limitations, this work introduces a novel strategy based on continuous chaotic bioprinting to create structured cocultures of probiotic bacteria. Using a Kenics static mixer–based printhead, we fabricated alginate hydrogel filaments with an internal multilayered microarchitecture containing four probiotic strains: Bifidobacterium bifidum, Bacteroides fragilis, Lactobacillus rhamnosus, and Streptococcus thermophilus.
The spatial arrangement of the multilayered architecture was designed to promote cooperative interactions, particularly by embedding strict anaerobes between facultative anaerobes to create self-sustaining hypoxic niches. The printed constructs were characterized over 72 h using fluorescence microscopy, colony-forming unit counts, LIVE/DEAD assays, qPCR, gas chromatography, and dynamic mechanic analysis. Results showed that structured cocultures exhibited higher viability, enhanced growth, and more balanced population dynamics than the monocultures of each bacterial strain and unstructured (scrambled) cocultures. Short-Chain Fatty Acid Production suggests functional cross-feeding; coculture filaments exhibited notably higher levels of acetic and propionic acids than the corresponding monocultures.
This study demonstrates that chaotic bioprinting enables precise spatial control over microbial ecosystems, allowing the rational design of microbial communities with tailored interactions.
Furthermore, chaotically printed constructs preserved probiotic viability for at least six weeks under storage, survived food-buffered gastric simulations, and maintained structural integrity over time, underscoring their robustness and translational potential. Chaotic bacterial bioprinting presents a powerful and scalable platform for next-generation probiotic production and opens new opportunities for engineered microbiomes, synthetic biology, and living material design.
{"title":"Bioprinting microbial harmony: Engineering spatially organized probiotic ecosystems via chaotic bioprinting","authors":"Francisco Javier Flores-Loera , Ariel Cantoral-Sánchez , Luis Fernando Carmona-Ramirez , Ilsa Pamela de los Santos-Hernández , Saulo Montaño-Medina , David Cantú-Fernández , Esther Pérez-Carrillo , José Rodríguez-Rodríguez , Claudia Maribel Luna-Aguirre , Francisco Javier Sierra-Valdez , Grissel Trujillo-de Santiago , Mario Moisés Alvarez","doi":"10.1016/j.bprint.2025.e00453","DOIUrl":"10.1016/j.bprint.2025.e00453","url":null,"abstract":"<div><div>Probiotic therapies offer great potential for addressing gut dysbiosis, but current approaches are limited by low strain diversity, high production costs, and the challenges of culturing strict anaerobes. To overcome these limitations, this work introduces a novel strategy based on continuous chaotic bioprinting to create structured cocultures of probiotic bacteria. Using a Kenics static mixer–based printhead, we fabricated alginate hydrogel filaments with an internal multilayered microarchitecture containing four probiotic strains: <em>Bifidobacterium bifidum</em>, <em>Bacteroides fragilis</em>, <em>Lactobacillus rhamnosus</em>, and <em>Streptococcus thermophilus</em>.</div><div>The spatial arrangement of the multilayered architecture was designed to promote cooperative interactions, particularly by embedding strict anaerobes between facultative anaerobes to create self-sustaining hypoxic niches. The printed constructs were characterized over 72 h using fluorescence microscopy, colony-forming unit counts, LIVE/DEAD assays, qPCR, gas chromatography, and dynamic mechanic analysis. Results showed that structured cocultures exhibited higher viability, enhanced growth, and more balanced population dynamics than the monocultures of each bacterial strain and unstructured (scrambled) cocultures. Short-Chain Fatty Acid Production suggests functional cross-feeding; coculture filaments exhibited notably higher levels of acetic and propionic acids than the corresponding monocultures.</div><div>This study demonstrates that chaotic bioprinting enables precise spatial control over microbial ecosystems, allowing the rational design of microbial communities with tailored interactions.</div><div>Furthermore, chaotically printed constructs preserved probiotic viability for at least six weeks under storage, survived food-buffered gastric simulations, and maintained structural integrity over time, underscoring their robustness and translational potential. Chaotic bacterial bioprinting presents a powerful and scalable platform for next-generation probiotic production and opens new opportunities for engineered microbiomes, synthetic biology, and living material design.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00453"},"PeriodicalIF":0.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.bprint.2025.e00446
Jéssica Heline Lopes da Fonseca , Ingri Julieth Mancilla Corzo , Rafael Abboud Azoubel , Rêner Pontes Tavares , Violeta Carvalho , Senhorinha F.C.F. Teixeira , José Luis Dávila , Marcos Akira d'Ávila
This study introduces and validates a custom load cell integrated into a 3D printer head for the in-situ measurement of pressures and rheological behavior during hydrogel printing in a piston-driven extrusion printer. In-situ force measurements were performed during extrusion of the three hydrogel formulations with distinct rheological properties to validate the load cell approach. The extrusion forces were converted into pressure values, and compared with predictions from analytical models, and further validated using Computational Fluid Dynamics (CFD) simulations, demonstrating a strong agreement. Apparent shear stress and viscosities were estimated from the extrusion force data using capillary rheometry principles and closely matched steady-shear values obtained from conventional rheometry. The load cell system was also used to investigate the effects of printing speed and needle diameter on extrusion behavior and print fidelity using CMC/CNC hydrogels. Higher printing speeds and narrower needle diameters resulted in increased extrusion pressures, significantly impacting shape fidelity. These findings are particularly relevant for 3D bioprinting, where real-time control of material properties is needed to balance resolution and cell viability.
{"title":"Real-time force and rheological measurement for hydrogels 3D bioprinting using a piston-driven extrusion system","authors":"Jéssica Heline Lopes da Fonseca , Ingri Julieth Mancilla Corzo , Rafael Abboud Azoubel , Rêner Pontes Tavares , Violeta Carvalho , Senhorinha F.C.F. Teixeira , José Luis Dávila , Marcos Akira d'Ávila","doi":"10.1016/j.bprint.2025.e00446","DOIUrl":"10.1016/j.bprint.2025.e00446","url":null,"abstract":"<div><div>This study introduces and validates a custom load cell integrated into a 3D printer head for the <em>in-situ</em> measurement of pressures and rheological behavior during hydrogel printing in a piston-driven extrusion printer. In-situ force measurements were performed during extrusion of the three hydrogel formulations with distinct rheological properties to validate the load cell approach. The extrusion forces were converted into pressure values, and compared with predictions from analytical models, and further validated using Computational Fluid Dynamics (CFD) simulations, demonstrating a strong agreement. Apparent shear stress and viscosities were estimated from the extrusion force data using capillary rheometry principles and closely matched steady-shear values obtained from conventional rheometry. The load cell system was also used to investigate the effects of printing speed and needle diameter on extrusion behavior and print fidelity using CMC/CNC hydrogels. Higher printing speeds and narrower needle diameters resulted in increased extrusion pressures, significantly impacting shape fidelity. These findings are particularly relevant for 3D bioprinting, where real-time control of material properties is needed to balance resolution and cell viability.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00446"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-28DOI: 10.1016/j.bprint.2025.e00445
Jieun Baek , Yudong Hong , Donghyun Lee , Ashley Hyomin Roh , C-Yoon Kim , Hyung Min Chung , Ji-Heon Lee , KyoungWhee Jeon
This study successfully established a full-thickness artificial skin model (CLE-iFTs) composed solely of human iPSC-derived fibroblasts (FBs) and keratinocytes (KCs) using a 3D bioprinting system. To evaluate the validity and performance of this model, we compared it with a manually fabricated counterpart (M-iPSC-FTs).
Quantitative analysis revealed that the keratinocyte proliferation rate in CLE-iFTs, as indicated by the percentage of Ki-67 positive cells (18.7 ± 1.2 %, p < 0.01), was significantly higher than in M-iPSC-FTs (9.7 ± 2.8 %). The basal epidermal marker KRT14 showed an average integrated density of 79,621.67 ± 3913.36 in CLE-iFTs and 75,442 ± 3913.36 in M-iPSC-FTs (p < 0.05), while the suprabasal marker KRT10 exhibited an integrated density of 247,260.33 ± 15,570.34 and 193,760 ± 24,214.66, respectively (p < 0.01), indicating stronger epidermal differentiation in the bioprinted model.
In addition, the dermis of CLE-iFTs demonstrated faster cell proliferation and higher cellular density compared to the manual model. Functional assessments further revealed that CLE-iFTs exhibited greater resistance to chemically induced cytotoxicity (IC50 value: 3.087 mg/mL vs. 2.761 mg/mL, p < 0.05) and a more favorable response to UVB irradiation, as evidenced by lower MMP-1 expression (p < 0.001) and higher Pro-collagen levels (p < 0.01).
In conclusion, the CLE-iFTs model provides superior reproducibility, enhanced structural integrity, and improved functional performance compared to manually fabricated models. These results highlight the potential of CLE-iFTs as a robust and reliable platform for advanced skin research, disease modeling, and regenerative medicine applications.
{"title":"Development of iPSC-derived full-thickness human skin via droplet-based 3D bioprinting","authors":"Jieun Baek , Yudong Hong , Donghyun Lee , Ashley Hyomin Roh , C-Yoon Kim , Hyung Min Chung , Ji-Heon Lee , KyoungWhee Jeon","doi":"10.1016/j.bprint.2025.e00445","DOIUrl":"10.1016/j.bprint.2025.e00445","url":null,"abstract":"<div><div>This study successfully established a full-thickness artificial skin model (CLE-iFTs) composed solely of human iPSC-derived fibroblasts (FBs) and keratinocytes (KCs) using a 3D bioprinting system. To evaluate the validity and performance of this model, we compared it with a manually fabricated counterpart (M-iPSC-FTs).</div><div>Quantitative analysis revealed that the keratinocyte proliferation rate in CLE-iFTs, as indicated by the percentage of Ki-67 positive cells (18.7 ± 1.2 %, p < 0.01), was significantly higher than in M-iPSC-FTs (9.7 ± 2.8 %). The basal epidermal marker KRT14 showed an average integrated density of 79,621.67 ± 3913.36 in CLE-iFTs and 75,442 ± 3913.36 in M-iPSC-FTs (p < 0.05), while the suprabasal marker KRT10 exhibited an integrated density of 247,260.33 ± 15,570.34 and 193,760 ± 24,214.66, respectively (p < 0.01), indicating stronger epidermal differentiation in the bioprinted model.</div><div>In addition, the dermis of CLE-iFTs demonstrated faster cell proliferation and higher cellular density compared to the manual model. Functional assessments further revealed that CLE-iFTs exhibited greater resistance to chemically induced cytotoxicity (IC<sub>50</sub> value: 3.087 mg/mL vs. 2.761 mg/mL, p < 0.05) and a more favorable response to UVB irradiation, as evidenced by lower MMP-1 expression (p < 0.001) and higher Pro-collagen levels (p < 0.01).</div><div>In conclusion, the CLE-iFTs model provides superior reproducibility, enhanced structural integrity, and improved functional performance compared to manually fabricated models. These results highlight the potential of CLE-iFTs as a robust and reliable platform for advanced skin research, disease modeling, and regenerative medicine applications.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"52 ","pages":"Article e00445"},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-07-30DOI: 10.1016/j.bprint.2025.e00429
Kentaro Umemori, Dianne Little
Tissue engineering frequently employs biomimetic scaffolds to direct cell responses and facilitate the differentiation of cells into specific lineages. Biodegradable scaffolds mitigate immune responses, stress shielding concerns in load bearing tissues, and the need for secondary or revision surgical procedures for retrieval. However, during the degradation process, scaffold properties such as fiber diameter, fiber porosity, fiber alignment, surface properties and mechanical properties undergo changes that significantly alter the initial properties. This review aims to comprehensively assess the impact of degradation on scaffold properties from the perspective of their effects on cellular behavior by addressing four key aspects of polymer degradation: First, we review the variables that influence scaffold degradation. Second, we examine how degradation impacts scaffold properties. Third, we explore the effects of scaffold degradation products. Finally, we investigate measures to increase tunability of degradation rate. Harnessing and incorporating these degradation mechanisms into scaffold design holds great promise for advancing the development of tissue-engineered scaffolds, ultimately improving their efficacy and clinical utility.
{"title":"Impact of Polymer Degradation on Cellular Behavior in Tissue Engineering.","authors":"Kentaro Umemori, Dianne Little","doi":"10.1016/j.bprint.2025.e00429","DOIUrl":"10.1016/j.bprint.2025.e00429","url":null,"abstract":"<p><p>Tissue engineering frequently employs biomimetic scaffolds to direct cell responses and facilitate the differentiation of cells into specific lineages. Biodegradable scaffolds mitigate immune responses, stress shielding concerns in load bearing tissues, and the need for secondary or revision surgical procedures for retrieval. However, during the degradation process, scaffold properties such as fiber diameter, fiber porosity, fiber alignment, surface properties and mechanical properties undergo changes that significantly alter the initial properties. This review aims to comprehensively assess the impact of degradation on scaffold properties from the perspective of their effects on cellular behavior by addressing four key aspects of polymer degradation: First, we review the variables that influence scaffold degradation. Second, we examine how degradation impacts scaffold properties. Third, we explore the effects of scaffold degradation products. Finally, we investigate measures to increase tunability of degradation rate. Harnessing and incorporating these degradation mechanisms into scaffold design holds great promise for advancing the development of tissue-engineered scaffolds, ultimately improving their efficacy and clinical utility.</p>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"50 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-26DOI: 10.1016/j.bprint.2025.e00443
Nan Zhang , Imtiaz Qavi , Marco Araneda , Shaida Sultana Rumi , Noureddine Abidi , Sampa Halder , George Z. Tan
Three-dimensional (3D) bioprinting has emerged as a powerful tool for fabricating engineered living materials (ELMs). Despite recent advances in controlling the spatial distribution of bacteria in hydrogel, printing bacteria-laden hydrogels into bulk 3D structures remains a significant challenge. This study presents a partial crosslinking bioprinting strategy for fabricating bacterial cellulose (BC)-based living scaffolds using sodium alginate (SA) hydrogels embedded with Komagataeibacter xylinus. Pre-crosslinked SA was first printed to define the scaffold outline, followed by infilling with uncrosslinked, bacteria-laden SA bioink to enable in situ BC nanofiber production. As BC nanofibers formed within the hydrogel, the scaffolds exhibited self-strengthening and self-hardening property. The effects of SA concentration and culture duration on cellulose yield, rheological properties, printability, and mechanical performance were systematically evaluated. Based on the quantitative relationship between hydrogel formulation, bacterial activity, and scaffold functionality, we optimized the bioinks to enable both high-resolution printing and efficient cellulose formation. This microbial bioprinting technique provides a robust platform for constructing functional BC-based ELMs with potential applications in biomedicine and tissue engineering.
{"title":"3D bioprinting of self-strengthening living materials using cellulose nanofiber-producing bacteria in sodium alginate hydrogel","authors":"Nan Zhang , Imtiaz Qavi , Marco Araneda , Shaida Sultana Rumi , Noureddine Abidi , Sampa Halder , George Z. Tan","doi":"10.1016/j.bprint.2025.e00443","DOIUrl":"10.1016/j.bprint.2025.e00443","url":null,"abstract":"<div><div>Three-dimensional (3D) bioprinting has emerged as a powerful tool for fabricating engineered living materials (ELMs). Despite recent advances in controlling the spatial distribution of bacteria in hydrogel, printing bacteria-laden hydrogels into bulk 3D structures remains a significant challenge. This study presents a partial crosslinking bioprinting strategy for fabricating bacterial cellulose (BC)-based living scaffolds using sodium alginate (SA) hydrogels embedded with <em>Komagataeibacter xylinus</em>. Pre-crosslinked SA was first printed to define the scaffold outline, followed by infilling with uncrosslinked, bacteria-laden SA bioink to enable in situ BC nanofiber production. As BC nanofibers formed within the hydrogel, the scaffolds exhibited self-strengthening and self-hardening property. The effects of SA concentration and culture duration on cellulose yield, rheological properties, printability, and mechanical performance were systematically evaluated. Based on the quantitative relationship between hydrogel formulation, bacterial activity, and scaffold functionality, we optimized the bioinks to enable both high-resolution printing and efficient cellulose formation. This microbial bioprinting technique provides a robust platform for constructing functional BC-based ELMs with potential applications in biomedicine and tissue engineering.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"51 ","pages":"Article e00443"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.bprint.2025.e00442
Fatemeh Saberi, Shohreh Mashayekhan
Developing an appropriate scaffold for cranioplasty applications remains challenging due to the high mechanical strength, controlled degradation, and support for cell migration and proliferation. Despite their common use, traditional materials such as titanium implants, bone allografts, hydroxyapatite, and poly methyl methacrylate have limitations that hinder their effectiveness. Achieving both robust mechanical performance and favorable biological properties in a single scaffold remains a significant challenge. In this study, we introduce a novel fabrication approach that combines 3D printing and directional freeze-casting to create a hybrid scaffold with enhanced structural and biological properties. A composite of polycaprolactone (PCL) and forsterite (FO) was 3D-printed to provide mechanical stability. Meanwhile, collagen and demineralized bone matrix (DBM) were freeze-cast into the pores to form radially aligned microchannels. This design enhances the biological properties and promotes cell migration by mimicking the native extracellular matrix architecture. Our results showed that adding 10 % forsterite to PCL increased the Young's modulus to 100 MPa, with 12 % degradation after one month of immersion in phosphate-buffered saline (PBS). The radially oriented collagen-DBM network supported a 2.4-fold increase in cell proliferation. Furthermore, the in vitro cell migration assay demonstrated enhanced cellular infiltration in aligned versus randomly structured scaffolds. Integrating a directional microstructure, chemical cues from ion release and DBM particles, along with a mechanically robust platform, offers a promising strategy for bone regeneration and cranioplasty applications.
{"title":"In vitro evaluation of 3D-printed PCL/forsterite scaffolds with aligned collagen and demineralized bone matrix for cranial bone regeneration","authors":"Fatemeh Saberi, Shohreh Mashayekhan","doi":"10.1016/j.bprint.2025.e00442","DOIUrl":"10.1016/j.bprint.2025.e00442","url":null,"abstract":"<div><div>Developing an appropriate scaffold for cranioplasty applications remains challenging due to the high mechanical strength, controlled degradation, and support for cell migration and proliferation. Despite their common use, traditional materials such as titanium implants, bone allografts, hydroxyapatite, and poly methyl methacrylate have limitations that hinder their effectiveness. Achieving both robust mechanical performance and favorable biological properties in a single scaffold remains a significant challenge. In this study, we introduce a novel fabrication approach that combines 3D printing and directional freeze-casting to create a hybrid scaffold with enhanced structural and biological properties. A composite of polycaprolactone (PCL) and forsterite (FO) was 3D-printed to provide mechanical stability. Meanwhile, collagen and demineralized bone matrix (DBM) were freeze-cast into the pores to form radially aligned microchannels. This design enhances the biological properties and promotes cell migration by mimicking the native extracellular matrix architecture. Our results showed that adding 10 % forsterite to PCL increased the Young's modulus to 100 MPa, with 12 % degradation after one month of immersion in phosphate-buffered saline (PBS). The radially oriented collagen-DBM network supported a 2.4-fold increase in cell proliferation. Furthermore, the in vitro cell migration assay demonstrated enhanced cellular infiltration in aligned versus randomly structured scaffolds. Integrating a directional microstructure, chemical cues from ion release and DBM particles, along with a mechanically robust platform, offers a promising strategy for bone regeneration and cranioplasty applications.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"51 ","pages":"Article e00442"},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.bprint.2025.e00441
Saumya Saraswat, Twinkle Bhargava, Juhi Landge, Kamalnayan Tibrewal
Global population growth, urbanization, and growing incomes have increased the need for protein, stressing the urgent need for sustainable alternatives to conventional livestock farming, which presents serious ethical, scalability, and environmental issues. Cultured meat, made by culturing animal cells under a controlled environment, is a possible alternative that can lower greenhouse gas emissions, land use, and animal suffering. However, large-scale production of cultured meat with the same texture, structure, and viability as conventional meat remains highly challenging. Even though three-dimensional (3D) bioprinting has become a crucial technique for precisely engineering meat-like, organized tissues, existing systems have hurdles with automation, repeatability, and throughput. The potential of recent (2020–2025) advancements in automation, Machine Learning (ML), and Artificial Intelligence (AI), primarily from the fields of regenerative medicine and tissue engineering, is examined in this paper along with its relevancy to large-scale cultured meat bioprinting.AI-driven process optimization, predictive modelling of cell viability and growth, real-time feedback through sensor-based control systems, robotic integration for material handling and post-processing, automated bioreactor integration, and early company adoption of AI and automation are some of the main topics. Research highlights advantages including less trial-and-error, improved accuracy with robotic systems, computer vision-based real-time print adjustments, and closed-loop feedback that requires less human engagement. The groundwork for intelligent, high-throughput "smart bioprinting factories" is laid by these technologies. This analysis maps out a route toward scalable, affordable cultured meat production with significant promise for industrial use and sustainable protein supply by combining advancements in AI, ML, and robotics.
{"title":"Towards intelligent cultivated/cultured meat factories: The synergy of AI, 3D bioprinting and automation in next-gen food manufacturing","authors":"Saumya Saraswat, Twinkle Bhargava, Juhi Landge, Kamalnayan Tibrewal","doi":"10.1016/j.bprint.2025.e00441","DOIUrl":"10.1016/j.bprint.2025.e00441","url":null,"abstract":"<div><div>Global population growth, urbanization, and growing incomes have increased the need for protein, stressing the urgent need for sustainable alternatives to conventional livestock farming, which presents serious ethical, scalability, and environmental issues. Cultured meat, made by culturing animal cells under a controlled environment, is a possible alternative that can lower greenhouse gas emissions, land use, and animal suffering. However, large-scale production of cultured meat with the same texture, structure, and viability as conventional meat remains highly challenging. Even though three-dimensional (3D) bioprinting has become a crucial technique for precisely engineering meat-like, organized tissues, existing systems have hurdles with automation, repeatability, and throughput. The potential of recent (2020–2025) advancements in automation, Machine Learning (ML), and Artificial Intelligence (AI), primarily from the fields of regenerative medicine and tissue engineering, is examined in this paper along with its relevancy to large-scale cultured meat bioprinting.AI-driven process optimization, predictive modelling of cell viability and growth, real-time feedback through sensor-based control systems, robotic integration for material handling and post-processing, automated bioreactor integration, and early company adoption of AI and automation are some of the main topics. Research highlights advantages including less trial-and-error, improved accuracy with robotic systems, computer vision-based real-time print adjustments, and closed-loop feedback that requires less human engagement. The groundwork for intelligent, high-throughput \"smart bioprinting factories\" is laid by these technologies. This analysis maps out a route toward scalable, affordable cultured meat production with significant promise for industrial use and sustainable protein supply by combining advancements in AI, ML, and robotics.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"51 ","pages":"Article e00441"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145098085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.bprint.2025.e00440
Lisa Schöbel , Mariya Tulchynska , Elmira Mohajeri , Christian Polley , Hermann Seitz , Jesus Gonzalez-Julian , Aldo R. Boccaccini
Electrically conductive hydrogels (ECHs) and electrical stimulation effectively regulate osteoblast attachment, proliferation, and differentiation, thus triggering bone tissue regeneration. Here, an alginate dialdehyde-gelatin (ADA-GEL) based hydrogel is modified with an electrically conductive and osteogenic 2D nanomaterial, namely MXene, to produce degradable and 3D printable nanocomposite hydrogels exhibiting electrical conductivity. The effect of MXene filler content on resulting hydrogel characteristics such as morphology, mechanical and electrical properties, swelling and degradation behavior was investigated comprehensively. The results indicate tailorable properties depending on MXene concentration, thus opening a library of ADA-GEL-MXene nanocomposite hydrogels. Moreover, the suitability of ADA-GEL-MXene hydrogels for 3D printing of grid-like scaffolds of up to 10 layers was shown. Additional 3D bioprinting studies demonstrated the applicability of the nanocomposite hydrogels as bioinks for 3D bioprinting of MG-63 osteoblast-like cells. Although the electrical conductivity was increased at higher MXene concentrations, compromised cell behavior was observed. This points to the conclusion that the concentration of MXene nanosheets must be carefully chosen depending on the required properties. Taken together, the presented ADA-GEL-MXene composite hydrogels exhibit significant potential for 3D bioprinting in bone tissue engineering and could be employed for the electrical stimulation of bone cells in the future.
{"title":"Oxidized alginate-gelatin nanocomposite hydrogels incorporating MXene nanosheets for 3D bioprinting","authors":"Lisa Schöbel , Mariya Tulchynska , Elmira Mohajeri , Christian Polley , Hermann Seitz , Jesus Gonzalez-Julian , Aldo R. Boccaccini","doi":"10.1016/j.bprint.2025.e00440","DOIUrl":"10.1016/j.bprint.2025.e00440","url":null,"abstract":"<div><div>Electrically conductive hydrogels (ECHs) and electrical stimulation effectively regulate osteoblast attachment, proliferation, and differentiation, thus triggering bone tissue regeneration. Here, an alginate dialdehyde-gelatin (ADA-GEL) based hydrogel is modified with an electrically conductive and osteogenic 2D nanomaterial, namely MXene, to produce degradable and 3D printable nanocomposite hydrogels exhibiting electrical conductivity. The effect of MXene filler content on resulting hydrogel characteristics such as morphology, mechanical and electrical properties, swelling and degradation behavior was investigated comprehensively. The results indicate tailorable properties depending on MXene concentration, thus opening a library of ADA-GEL-MXene nanocomposite hydrogels. Moreover, the suitability of ADA-GEL-MXene hydrogels for 3D printing of grid-like scaffolds of up to 10 layers was shown. Additional 3D bioprinting studies demonstrated the applicability of the nanocomposite hydrogels as bioinks for 3D bioprinting of MG-63 osteoblast-like cells. Although the electrical conductivity was increased at higher MXene concentrations, compromised cell behavior was observed. This points to the conclusion that the concentration of MXene nanosheets must be carefully chosen depending on the required properties. Taken together, the presented ADA-GEL-MXene composite hydrogels exhibit significant potential for 3D bioprinting in bone tissue engineering and could be employed for the electrical stimulation of bone cells in the future.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"51 ","pages":"Article e00440"},"PeriodicalIF":0.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}