Biofabrication最新文献

{"title":"Shape, shrink, spheroid: a DIY high-throughput spheroid generation device.","authors":"Pankaj Mogha, Sourav Mukherjee, Tushar Gangwar, Debjyoti Roy, Aditi Vichare, Swanand Kulkarni, Vineet Sharma, Abhijit Majumder","doi":"10.1088/1758-5090/ae8bdd","DOIUrl":"10.1088/1758-5090/ae8bdd","url":null,"abstract":"<p><p>3D spheroids, which closely replicate three-dimensional cell-cell and cell-extracellular matrix interactions, offer superior predictive capabilities compared to conventional 2D monolayer cultures, positioning them as forward-looking platforms in drug testing, cancer biology, and regenerative medicine. However, high-throughput generation of uniform sized spheroids is still a technological challenge. In one hand, the use of conventional ultra-low attachment (ULA) multiwell plates for this purpose is labor intensive and complex. On the other hand, the use of microfabricated facilities demands cutting-edge infrastructure such as clean room, photolithography, and microfluidic setup which are often unavailable for the resource constrained laboratories. In this study, we addressed these problems by developing a low-cost do-it-yourself (DIY), polydimethylsiloxane (PDMS) and agarose-based spheroid generation device, capable of producing and maintaining hundreds of spheroids with minimal user intervention. We have demonstrated two variants based on their size, termed here as S1 and S2 devices which fit into 6-well and 12-well plates, and can generate 600 and 1200 uniform-sized spheroids respectively. We validated our device with various cell lines including primary and cancerous cell lines. We further demonstrated the drug testing capabilities of the device by estimating the IC₅₀value of the anticancer drug Temozolomide on U87-MG. The value was comparable with the same obtained from the spheroids generated using conventional ULA plates. Additional attachment of a perfusion system made the device suitable for long-term spheroid culture without much user intervention. Furthermore, the devices can also be used for the production of spheroids with gradually changing diameters in a controlled manner, resembling a size gradient. This feature is useful for checking the effect of drugs on different-sized spheroids and for co-culturing spheroids with varying cell densities, mimicking the disease architecture. We have co-cultured two types of the placental trophoblast cells, i.e. extravillous trophoblast (HTR-8) and syncytiotrophoblast (BeWo) with varying densities. In summary, this paper demonstrates a unique DIY method for a high-throughput uniform-sized spheroid generation at a fraction of cost which can be deployed to resource-constrained labs.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468725","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":"Overcoming mass and heat transfer limitations in vitrification of large diffusion-limited tissues via volumetric electromagnetic rewarming.","authors":"Haiyang Ma, Josh Wewerka, Ge Pan, Minar Mahmud, A J Riffe, Dustin Mueller, Peng Chen, Yaqian Sun, Jian Chen, John M Alford, Yongren Wu, Kristi Helke, Girish Srinivas, Hai Yao, David P Eisenberg, Shangping Wang","doi":"10.1088/1758-5090/ae8bdc","DOIUrl":"10.1088/1758-5090/ae8bdc","url":null,"abstract":"<p><p>Long-term preservation of large, viable biological tissues remains a major hurdle in transplantation and regenerative medicine, particularly for dense, non-perfusable tissues that rely solely on diffusion for cryoprotectant (CPA) transport and heat transfer. Ice-free vitrification offers a promising solution but requires sufficient CPA penetration and rapid and spatially uniform rewarming to prevent devitrification, recrystallization, and thermomechanical damage. Here, we present a volumetric radiofrequency electromagnetic (RF-EM) rewarming platform integrated with diffusion-guided CPA loading to enable vitrification of large diffusion-limited tissues. Using porcine articular cartilage as a representative dense, avascular tissue model, micro-computed tomography-guided diffusion modeling and experimental optimization achieved >85% CPA penetration without cytotoxicity. Finite element thermal modeling and experimental validation demonstrated that RF-EM volumetric rewarming achieved warming rates exceeding 100 °C min^-1while reducing temperature gradients in 10 ml tissue samples to <10 °C, compared with >70 °C during conventional convective warming, thereby preventing thermal fracture and devitrification. When combined with optimized loading protocols, the integrated transport and rewarming approach preserved >90% cellular viability and supported metabolic recovery, with metabolic activity exceeding 80% by day 1 in 3 ml cartilage discs and exceeding 70% by day 3 in 10 ml cartilage pieces, followed by an increasing trend over the 5-day culture period. The approach also maintained extracellular matrix composition with >90% glycosaminoglycan retention, and retained native mechanical properties comparable to fresh controls. These findings demonstrate that volumetric RF-EM rewarming, coupled with diffusion-guided CPA loading, provides an engineering solution to mass and heat transfer limitations in vitrification of porcine cartilage tissues up to 10 ml, while modeling results suggest its potential scalability to larger tissue volumes, with potential applications in tissue banking, transplantation, and regenerative medicine.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468718","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":"Optimized scaffold-free chondrocyte-collagen-based cell sheets for hyaline cartilage regeneration in a porcine full-thickness knee defect model.","authors":"Chwen-Ru Lin, Chun-Yen Liu, Kuo-Hsiang Hung, Yan-Der Hsuuw, Yih-Wen Tarng","doi":"10.1088/1758-5090/ae8a83","DOIUrl":"10.1088/1758-5090/ae8a83","url":null,"abstract":"<p><p>Traumatic articular cartilage defects remain a significant clinical challenge due to their limited intrinsic self-repair capacity, inadequate structural support, and the frequent formation of fibrocartilaginous tissue rather than hyaline cartilage. Here, we established a scaffold-free cell sheet engineering strategy to fabricate a clinically sized, multilayer chondrocyte-collagen-based implant with favorable operability. By integrating fibronectin (FN) -type II collagen (COL II) nanocoating with optimized cell seeding density and a refined fabrication process, we generated a thick, three-dimensional multilayer chondrocyte sheet with robust interlayer cohesion, abundant extracellular matrix deposition, and high expression of hyaline cartilage markers, including COL II and aggrecan. This multilayer stacking strategy overcomes the intrinsic thickness limitation of single-layer sheets and enhances cartilage-specific ECM deposition and structural continuity, yielding a tissue architecture better suited for repairing larger or deeper cartilage defects and underscoring the clinical potential of multilayer chondrocyte-collagen-based cell sheets. In a porcine<i>in vivo</i>model of full-thickness knee cartilage defects, FN-0.05 mg ml^-1COL II-coated multilayer sheets promoted hyaline-like cartilage regeneration and seamless integration with the surrounding native tissue, while markedly reducing fibrocartilaginous repair. Accordingly, this study defines a scalable scaffold-free chondrocyte-collagen-based platform with enhanced structural stability and hyaline chondrogenic capacity, underscoring its translational potential for the repair of traumatic articular cartilage defects.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444266","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":"4D direct ink writing of body temperature-responsive triple-shape memory scaffolds for bone tissue engineering.","authors":"Nasim Sabahi, Iman Roohani, Kristopher A Kilian, Chun H Wang, Xiaopeng Li","doi":"10.1088/1758-5090/ae8a85","DOIUrl":"10.1088/1758-5090/ae8a85","url":null,"abstract":"<p><p>Four dimensional printing of shape memory polymers (SMPs) holds significant promise for addressing irregular bone defects. The incorporation of SMPs with the ability to adopt multiple shapes greatly enhances the performance of 4D-printed scaffolds. These smart scaffolds not only provide crucial structural support but also actively interact with cells to promote and enhance regenerative processes. In this study, we successfully developed novel triple-SMPs with two distinct transition temperatures (<i>T</i>_g= 34 °C and<i>T</i>_m= 56 °C). By melt blending biocompatible thermoplastics, including polycaprolactone, thermoplastic polyurethane, and Poly (lactic-co-glycolic acid) (PLGA), at different weight ratios, we achieved over 90% shape recovery ratios during two sequential recovery processes. Shape memory tests revealed that the weight ratio of PLGA in the polymer composition influenced the shape fixity and shape recovery of programmed structures at body temperature. Subsequently, the developed SMPs were utilized for 4D direct ink writing printing of smart bone scaffolds. The SMPs exhibited excellent printability, enabling successful printing at 220 °C and 200 kPa, resulting in 3D-printed scaffolds with uniform and interconnected pore distribution, ensuring structural integrity. Furthermore, the 4D-printed scaffolds demonstrated outstanding degradability, biocompatibility, and mechanical properties comparable to human trabecular bone. This work presents a robust and feasible approach for 4D printing of triple-shape memory bone scaffolds, offering a promising solution for complex irregular bone defects.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444237","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":"Too big, too small, too O2: the Pandoro effect from oxygen gradients in tomographic volumetric additive manufacturing.","authors":"Riccardo Rizzo, Felix Wechsler, Qianyi Zhang, Christophe Moser","doi":"10.1088/1758-5090/ae8a84","DOIUrl":"10.1088/1758-5090/ae8a84","url":null,"abstract":"<p><p>Tomographic volumetric additive manufacturing (TVAM) enables rapid, layerless biofabrication; however, its application to thermoreversible hydrogels is often compromised by complex photochemical kinetics such as inhibitor effects including varying concentration and diffusion. In this study, we identify and characterize a recurrent printing artifact-termed the<i>Pandoro effect</i>-manifesting as a truncated-cone distortion caused by premature polymerization at the vial bottom and inhibition at the top. We demonstrate that this phenomenon originates from a vertical oxygen gradient driven by the thermal cycling of resin preparation: heating depletes dissolved oxygen, while subsequent cooling induces diffusion-limited re-oxygenation from the air-resin interface. To mitigate this, we present a multi-tiered strategy. First, we introduce a coupled ray-optical and photochemical optimization model that rigorously accounts for spatially heterogeneous inhibitor concentrations. Unlike conventional threshold-based approaches, this differentiable framework explicitly simulates the spatiotemporal reaction-diffusion dynamics of oxygen depletion, allowing the inverse solver to predictively compensate for local inhibition gradients. Complementing this algorithmic correction, we validate two process-based interventions: the elimination of the air-resin interface and the control of headspace atmosphere. We demonstrate that these strategies effectively suppress the<i>Pandoro effect</i>and are compatible with cell-laden resins. This work establishes guidelines for reproducible volumetric bioprinting and expands our open-source Dr.TVAM platform with inhibition-aware polymerization modeling capabilities.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D bioprinting of functional meniscus constructs with anisotropic properties using meniscus-derived bioink for knee meniscus regeneration.","authors":"Sung-Sahn Lee, Suhun Chae, Young-Sik Jeon, Kyeu Back Kwon, Jiyun Seo, Yeong-Jin Choi, Ge Gao, Wonbin Park, Dong-Woo Cho, Joon Ho Wang","doi":"10.1088/1758-5090/ae8b2c","DOIUrl":"10.1088/1758-5090/ae8b2c","url":null,"abstract":"<p><p>Meniscal injuries frequently result in progressive degeneration of the knee joint, primarily due to the tissue's limited intrinsic healing capacity. To address this clinical challenge, we developed an anisotropic meniscus scaffold using three-dimensional (3D) bioprinting technology to promote functional regeneration. In this study, the scaffold was fabricated via 3D bioprinting, employing a composite of polyurethane and polycaprolactone polymers, meniscus derived decellularized extracellular matrix bioink, and mesenchymal stem cells (MSCs).<i>In vitro</i>, the bioprinted constructs, incorporating tissue-derived bioinks with region-specific stiffness, facilitated the differentiation of MSCs and extracellular matrix deposition in a manner that recapitulated the native anisotropic architecture of the meniscus.<i>In vivo</i>, the constructs demonstrated excellent chondroprotective effects and supported neo-meniscus formation in a canine model at 12 and 24 weeks post-implantation. These findings suggest that the engineered 3D bioprinted meniscus scaffold holds strong potential for clinical application in meniscal repair and regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454429","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":"IntravChip: a vascularized and perfused microfluidic model of the primary tumor microenvironment to collect intravasated tumor cells.","authors":"Marie Floryan, Alessandro Cordiale, Heather Jensen, Julie Chen, Zixian Guo, Vinayak Vinayak, Sina Kheiri, Ritu Raman, Vivek Shenoy, Elena Cambria, Roger Kamm","doi":"10.1088/1758-5090/ae8721","DOIUrl":"10.1088/1758-5090/ae8721","url":null,"abstract":"<p><p>Hematogenous metastasis is initiated when tumor cells (TCs) intravasate into the vasculature, yet intravasation remains poorly understood because it is difficult to observe<i>in vivo</i>and intravasated TCs are challenging to isolate. To address these challenges, we developed IntravChip, a continuously perfused microfluidic platform containing a vascularized primary tumor microenvironment (TME) enabling the observation of TC intravasation, and a downstream chamber to collect intravasated TCs. The IntravChip can support a high TC concentration in the TME while maintaining complete vascular perfusion, which we found was necessary to collect intravasated cells. Using MDA-MB-231 breast TCs, we identified an optimal initial TC seeding density that, by day 9, yields a densely populated TME and 100-440 collected intravasated TCs. We validated the IntravChip across several TC types, showing that MDA-MB-231 and MV3 TCs have the highest intravasation rates while MCF-7 TCs have low intravasation efficiency. We also show that the IntravChip is compatible with super-resolution nano-imaging. Our devices enabled high-quality STochastic Optical Reconstruction Microscopy imaging, which revealed that H3K9me3 nanodomains are significantly differentially distributed in intravasated MDA-MB-231 TCs compared to those residing in the TME. Finally, the IntravChip was validated as a platform to test the effects of anti-cancer drugs on TCs and on the vasculature. We showed that a 5<i>μ</i>M concentration of sorafenib reduced intravasation events by 69% without impacting the morphology of the microvascular networks, while a 10<i>μ</i>M concentration led to a significant decrease in vessel diameter. This platform enables quantitative analysis of TC intravasation, collection of intravasated TCs for characterization, and screening of anti-metastatic therapies.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403390","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":"Engineering the esophagus: advances, challenges, and translational pathways in esophageal tissue reconstruction.","authors":"Alireza Nemati, Anu David, Yuxuan Zhang, Houman Savoji, Christophe Faure","doi":"10.1088/1758-5090/ae80ff","DOIUrl":"10.1088/1758-5090/ae80ff","url":null,"abstract":"<p><p>Esophageal reconstruction is one of the most challenging procedures in gastrointestinal surgery. While conventional therapeutic approaches, such as gastric pull-up and intestinal interposition, can restore continuity, they often fail to replicate native physiology. This limitation frequently leads to long-term complications, including dysphagia, stricture, and reflux, which can significantly affect the patients' quality of life. Tissue engineering approaches offer promising alternatives aimed at developing esophageal constructs that restore both structure and function, addressing the shortcomings of current treatment methods. This review highlights recent progress in esophageal tissue engineering (ETE), focusing on the requirements for ideal ETE scaffolds and examining available biomaterials, including natural, synthetic, and hybrid. We discuss advances in fabrication techniques and various cell-based approaches, such as primary cells, stem cells, and organoids. Furthermore, we also review the steps necessary to transition ETE constructs from the laboratory to clinical settings (ongoing human trials), including preclinical studies conducted on rodent, rabbit, canine, and porcine models with the expected functional outcomes and regeneration capabilities. Early translational efforts in ETE are addressed, along with the regulatory and ethical considerations regarding good manufacturing practice (GMP) compliance, traceability, and long-term surveillance. While significant advancements in ETE have been made in preclinical models, the review also discusses the challenges of moving to clinical studies. Potential strategies to address these challenges, such as 4-dimensional printing, smart materials, artificial intelligence-driven scaffold optimization, and organoid-based models, are introduced to help bridge the gap from preclinical research to successful clinical trials. In summary, ETE is transitioning from an experimental advancement to a translational reality by integrating significant achievements in biomaterials, fabrication technologies, and cell biology while following health regulatory standards. These efforts aim to provide regenerative solutions that overcome the limitations of current therapeutic approaches in clinical settings, ultimately facilitating healing and improving the patients' quality of life.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306907","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":"CAR-T cell-derived exosomes and cancer immunotherapy: advancing production and delivery through biofabrication.","authors":"Mahmood Razzaghi, Mohammad Hossein Karimi, Jamshid Hadjati, Colin Collins, Mohsen Akbari","doi":"10.1088/1758-5090/ae7b0b","DOIUrl":"10.1088/1758-5090/ae7b0b","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematologic malignancies, but it still faces major barriers in solid tumors due to poor infiltration, an immunosuppressive microenvironment, and sometimes severe toxicities. CAR-T cell-derived exosomes (CAR-T-EXOs) have emerged as a potentially safer, more scalable acellular alternatives that preserve tumor-specific CAR recognition and cytotoxic functions while potentially reducing risks such as cytokine release syndrome and neurotoxicity. These nanosized vesicles can penetrate the dense tumor stroma and reprogram the immunosuppressive niches potentially more effectively than the cellular therapies. The recent advances in biofabrication are now enabling the high-yield production, functional validation, and more precise delivery of CAR-T-EXOs. The biofabricated models, including the three-dimensional spheroids, organoids, bioprinted constructs, and tumor-on-chip (ToC) systems, offer more physiologically relevant platforms for evaluating exosome trafficking and efficacy. Meanwhile, smart delivery systems such as stimuli-responsive hydrogels, nanofiber scaffolds, and hybrid nanovesicles provide spatiotemporal control over the exosome release. Despite all these promises, clinical translation is still hindered by the variability in isolation methods, characterization procedures, and regulatory frameworks. This review tries to integrate immunology, bioengineering, and translational perspectives to outline the biological advantages of the CAR-T-EXOs, to survey the latest biofabrication strategies, and to discuss the regulatory challenges. We also highlight some emerging paradigms, like exosome mimetics, nanorobotics, and personalized ToC testing, that are likely to speed up the next generation of safer and more effective exosome-based immunotherapies for solid tumors.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209990","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":"Inorganic biomaterials-reinforced printable hydrogel modulating regenerative microenvironments for tissue repair.","authors":"Ziyi Zhao, Chengtie Wu","doi":"10.1088/1758-5090/ae8580","DOIUrl":"10.1088/1758-5090/ae8580","url":null,"abstract":"<p><p>Complex tissue/organ regeneration is a well-orchestrated biological process that is orchestrated by the coordinated effort of neural, vascular and immune systems, accompanied by multiple cellular interactions and signal crosstalk. The beneficial pro-regenerative microenvironments are of great significance for regulating tissue-resident cell viability, migration and differentiation to direct tissue repair process. 3D bioprinting is an advanced biomanufacturing strategy that utilizes hydrogel-containing bioinks to fabricate cell-laden scaffolds, but they face the limitations of insufficient bioactivity. Inorganic biomaterials have been recognized as effective bioactive agents owing to their tunable chemical composition, topographical architectures, and physiochemical properties, which can overcome the limitation of printable hydrogel and broaden their potential biological applications. This review primarily focuses on the design of inorganic biomaterials-reinforced printable hydrogel for modulating regenerative microenvironments including neural, vascular, and immune regulation, as well as summarizes the recent progress of their applications for tissue and organ regeneration. It begins with an introduction of inorganic biomaterials augmenting the biophysical and the biochemical properties of 3D-printed hydrogel, especially highlighting the improvement of topographical cues, mechanical strength, external field responsiveness, and bioactive components release for regulating various tissue microenvironments. Subsequently, recent advancements of inorganic biomaterials-reinforced printable hydrogel in regenerating musculoskeletal system, skin, and cardiac tissues are systematically reviewed. Finally, current challenges and future perspectives in the development of inorganic biomaterials-reinforced printable hydrogel are proposed. This review may offer a novel insight for the design of novel bioinks in combination with inorganic biomaterials and printable hydrogel, which shows great potential for engineered biofabrication and complex tissue/organ regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374392","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}