Search Results (10)

Magnetic cell assembly has emerged as a powerful biofabrication strategy that uses externally applied magnetic fields to manipulate and organize living cells with spatial control, enabling the fabrication of scaffold-free multicellular constructs while preserving cell viability and function. Advances in magnetic nanoparticles, cell labeling techniques, and magnetic field engineering have expanded its applications from rapid spheroid formation to the assembly of complex, spatially organized tissues. This review provides a comprehensive overview of the fundamental principles governing magnetic cell assembly, including the generation of magnetically responsive cells, magnetic force-mediated manipulation, and the biological processes driving tissue formation after magnetic assembly. We discuss the major assembly strategies, including magnetic aggregation, levitation, patterning, alignment, and modular tissue assembly, highlighting their underlying mechanisms, representative studies, engineering advantages, and current limitations. Recent progress in musculoskeletal, cardiovascular, neural, and vascular tissue engineering, as well as organoid and assembloid technologies, disease modeling, and drug discovery, is critically evaluated with an emphasis on experimental outcomes and remaining challenges. Particular attention is given to how magnetic cell assembly has evolved from a technique for manipulating individual cells into a programmable platform for organizing living building blocks with increasing structural and biological complexity. Finally, we discuss the key obstacles to clinical translation, including vascularization, tissue maturation, scalability, reproducibility, and standardization, together with future opportunities arising from the integration of magnetic cell assembly with bioprinting, stem cell engineering, microphysiological systems, and artificial intelligence. This review highlights the potential of magnetic cell assembly as an enabling technology that bridges magnetism and biofabrication to engineer next-generation living tissue models. Full article

Tissue engineering and regenerative medicine are shifting from passive tissue replacement toward instructive platforms that regulate cellular behavior, immune responses, vascularization, and extracellular matrix remodeling. This review examines recent advances in natural, synthetic, composite, and stimuli-responsive biomaterials, biofabrication and 3D bioprinting, stem and progenitor cell therapies, extracellular vesicles and other cell-free products, immunomodulatory scaffolds, skin organoids and organ-on-a-chip systems, nanotechnology, and artificial intelligence-assisted design. Particular emphasis is placed on plastic, reconstructive, and aesthetic applications, including skin and wound repair, craniofacial bone and cartilage regeneration, peripheral nerve reconstruction, vascularization, and dental and periodontal repair. The review also considers biomodulators and skinboosters as emerging regenerative-aesthetic interventions that aim to improve dermal hydration, fibroblast activity, collagen remodeling, and skin quality rather than provide volume replacement alone. Importantly, these technologies differ substantially in translational maturity, ranging from in vitro and preclinical platforms to early clinical interventions, established clinical products, and commercially available treatments for which durable regenerative efficacy remains incompletely validated. Throughout this review, biological plausibility and preclinical efficacy are therefore distinguished from human clinical evidence, regulatory or established clinical use, and commercial availability. Progress will require standardized characterization, mechanism-linked potency assays, clinically relevant models, and outcome measures that capture functional integration, durability, safety, and aesthetic performance. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

Volumetric muscle loss (VML) constitutes a significant clinical challenge, defined by the irreversible loss of skeletal muscle tissue and resulting in persistent functional deficits due to fibrosis, chronic inflammation, and insufficient endogenous regeneration. Existing clinical interventions, such as autologous grafting and free functional muscle transfer, are constrained by donor-site morbidity including infection, pain, suboptimal vascularization, and limited functional integration. Although tissue engineering has advanced considerably, no FDA-approved regenerative therapies currently exist for VML, underscoring a substantial translational gap. This review provides a systems-level synthesis of skeletal muscle repair through integrating fundamental biological processes, such as inflammation, satellite-cell activation, myogenesis, angiogenesis, and neuromuscular junction formation, with recent advances in biomaterials, scaffold engineering, and biofabrication technologies. The analysis addresses how critical scaffold design parameters, including alignment, porosity, stiffness, degradation kinetics, and bioactivity, influence cellular responses and tissue integration. Additionally, emerging strategies such as 3D bioprinting, nanofiber-based architectures, stem cell and exosome therapies, and bio-functional stimulation are evaluated inside a unified mechanobiological framework. This analysis is further extended to the regulatory setting, with emphasis on how scaffold composition, mechanism of action, and degree of biological integration affect classification pathways governed by the U.S. Food and Drug Administration. Most advanced VML therapies are anticipated to be regulated as combination products, which will require rigorous preclinical validation, standardized manufacturing processes, and carefully designed clinical studies. By integrating biological principles, engineering design, and regulatory considerations, this review highlights key opportunities, remaining challenges, and future priorities for the clinical translation of next-generation regenerative strategies for VML. Full article

The growing global demand for ethical, resource-efficient protein sources has renewed serious interest in cultured meat as a viable alternative to conventional livestock production. Two revolutionary biotechnological systems, induced pluripotent stem cell (iPSC) reprogramming and CRISPR-Cas9-mediated genome editing, when combined, offer unparalleled accuracy and scalability for the biofabrication of avian flesh. In this review, we present a comprehensive pipeline that involves the ectopic expression of Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) to reprogram primary somatic cells derived from Gallus gallus into induced pluripotent stem cells (iPSCs). This process is subsequently followed by targeted genome editing to enhance myogenic potential, growth efficiency, nutritional composition, and disease resistance. iPSCs are cultivated in a xeno-free bioreactor following genome editing, and subsequently directed to develop into myoblasts and mature myotubes. Three-dimensional tissue biofabrication is realized by combining biomaterial scaffolds and perfusion bioreactor systems, structuring an authentic muscle tissue matrix. These engineering platforms enable precise control over microenvironmental parameters, including oxygenation and nutrient perfusion. The resulting biofabricated poultry product is compositionally optimized, free of antibiotic residues, and exhibits a significantly reduced environmental footprint than poultry that is grown in the traditional way. This all-in-one solution solves important problems in food security, animal welfare, land use efficiency, and greenhouse gas emissions while also setting up a scalable biomanufacturing framework for making proteins for the next generation. Full article

Three-dimensional (3D) cell culture models more faithfully reproduce native tissue organization and function than conventional two-dimensional systems, yet many existing bioprinting methods depend on scaffolds, complex instrumentation, or limited control over cell positioning. This review examines magnetic bioinks as a versatile platform for contactless 3D cell manipulation and biofabrication. It first outlines the fundamentals of magnetophoresis and defines magnetic bioinks as combinations of magnetic agents, including magnetic nanoparticles or paramagnetic salts, with biological components such as cells, proteins, or fluids. The review then compares label-based strategies, in which cells are magnetized and guided by positive magnetophoresis, with label-free approaches that exploit magnetic susceptibility differences to position diamagnetic cells through negative magnetophoresis. Across these methods, magnetic bioinks have enabled single-cell sorting, spatial patterning, spheroid and co-culture assembly, multilayer tissue formation, and hydrogel-integrated printing. These capabilities support applications in disease modeling, drug screening, biosensing, regenerative medicine, and emerging biofabrication under microgravity conditions. The paper also highlights key limitations, including nanoparticle biocompatibility, paramagnetic salt toxicity, osmotic stress, and the need for better assay standardization and translational validation. Overall, magnetic bioinks represent a promising scaffold-free approach for rapidly producing physiologically relevant 3D biological constructs for research and clinical innovation. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment. Full article

Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration. Full article

Top-down tissue engineering aims to produce functional tissues using biomaterials as scaffolds, thus providing cues for cell proliferation and differentiation. Conversely, the bottom-up approach aims to precondition cells to form modular tissues units (building-blocks) represented by spheroids. In spheroid culture, adult stem cells are responsible for their extracellular matrix synthesis, re-creating structures at the tissue level. Spheroids from adult stem cells can be considered as organoids, since stem cells recapitulate differentiation pathways and also represent a promising approach for identifying new molecular targets (biomarkers) for diagnosis and therapy. Currently, spheroids can be used for scaffold-free (developmental engineering) or scaffold-based approaches. The scaffold promotes better spatial organization of individual spheroids and provides a defined geometry for their 3D assembly in larger and complex tissues. Furthermore, spheroids exhibit potent angiogenic and vasculogenic capacity and serve as efficient vascularization units in porous scaffolds for bone tissue engineering. An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication. Full article