Search Results (439)

Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of providing a three-dimensional, biomimetic scaffold that supports cell viability, spatial organization, and dynamic signaling. Natural polymer-based hydrogels, derived from materials such as collagen, gelatin, hyaluronic acid, and alginate, offer favorable properties including biocompatibility, degradability, and an extracellular matrix-like architecture. This review presents recent advances in the design and application of such hydrogels, focusing on crosslinking strategies (physical, chemical, and hybrid), the viscoelastic characteristics, and stimuli-responsive behaviors. The influence of these materials on cellular processes, such as stemness maintenance, differentiation, and morphogenesis, is critically examined. Furthermore, the applications of organoid culture and dynamic MPS platforms are discussed, highlighting their roles in morphogen delivery, barrier formation, and vascularization. Current challenges and future perspectives toward achieving standardized, scalable, and translational hydrogel systems are also addressed. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research. Polylactic acid scaffolds with physiological (P) and osteoporotic-like (O) trabecular architectures were 3D-printed by means of fused deposition modeling technology. Morphometric characterization was performed using micro-computed tomography. Human osteoblast-like SAOS-2 and U2OS cells were cultured on the scaffolds under static and dynamic simulated microgravity conditions using a rotary cell culture system (RCCS). Scaffold biocompatibility, cell viability, adhesion, and metabolic activity were evaluated through Bromodeoxyuridine incorporation assays, a water-soluble tetrazolium salt assay, and an enzyme-linked immunosorbent assay of tumor necrosis factor-α secretion. Both scaffold models supported osteoblast-like cell adhesion and growth, with an approximately threefold increase in colonization observed on the high-porosity O scaffolds under dynamic conditions. The dynamic environment facilitated increased surface interaction, amplifying the effects of scaffold architecture on cell behavior. Overall, sustained cell growth and metabolic activity, together with the absence of detectable inflammatory responses, confirmed the biocompatibility of the system. Scaffold microstructure and dynamic culture conditions significantly influence osteoblast-like cell behavior. The combination of 3D-printed scaffolds and a RCCS bioreactor provides a promising platform for studying bone remodeling in osteoporosis and microgravity-induced bone loss. These findings may contribute to the development of advanced in vitro models for biomedical research and potential countermeasures for bone degeneration. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Tracheal reconstruction remains a formidable clinical challenge, particularly for long-segment defects that are not amenable to standard surgical resection or primary anastomosis. Tissue engineering has emerged as a promising strategy for restoring the tracheal structure and function through the integration of biomaterials, stem cells, and bioactive molecules. This review provides a comprehensive overview of recent advances in tissue-engineered tracheal grafts, particularly in scaffold design, cellular sources, fabrication technologies, and early clinical experience. Innovations in biomaterial science, three-dimensional printing, and scaffold-free fabrication approaches have broadened the prospects for patient-specific airway reconstruction. However, persistent challenges, including incomplete epithelial regeneration and mechanical instability, have hindered its clinical translation. Future efforts should focus on the design of modular biomimetic scaffolds, the enhancement of immunomodulatory strategies, and preclinical validation using robust large animal models. Sustained interdisciplinary collaboration among surgical, engineering, and biological fields is crucial for advancing tissue-engineered tracheal grafts for routine clinical applications. Within this context, biomimetic approaches, including three-dimensional bioprinting, hybrid materials, and scaffold-free constructs, are gaining prominence as strategies to replicate the trachea’s native architecture and improve graft integration. Full article

Bioactive materials have recently shown potential in nerve repair and regeneration by promoting the growth of new cells, tissue repair, and restoring nerve function. These natural, synthetic, and hybrid materials offer a biomimetic structure, enhance cell attachment, and release bioactive molecules that promote the axonal extension of severed nerves. Scaffold-based preclinical studies have shown promising results on enhancing nerve repair; however, they are limited by the immune response and fabrication, scalability, and cost. Nevertheless, advances in manufacturing, including 3D bioprinting, and other strategies, such as gene editing by CRISPR, will overcome these shortcomings. The opportunity for the development of individualized approaches and specific treatment plans for each patient will also increase the effectiveness of bioactive materials for the treatment of nerve injuries. Combining bioactive materials with the neural interface can develop new reliable therapeutic solutions, particularly for neuroprosthetics. Finally, it is essential to stress a multidisciplinary focus, and future studies are needed to enhance the potential of bioactive materials for patients with nerve injuries and the field of regenerative medicine. Full article

Electrospun fibers, possessing biomimetic characteristics similar to fibrous extracellular matrices, have attracted widespread attention as scaffold materials for skin tissue engineering. The topographical structure of electrospun fibers plays a critical role in determining cell behavior. However, the effects of fiber topography on human skin fibroblasts (HSFs) remain unclear. In this study, electrospinning technology was employed to investigate how parallel and crossed fiber architectures influence the spreading morphology, proliferation, and migration of HSFs. The results demonstrated that cells exhibited spindle-shaped elongation along single fibers; on closely spaced parallel fibers, cells formed cross-adhesions between adjacent fibers, with a fiber spacing of 30–60 μm serving as the threshold range for distinguishing individual cell behaviors. At fiber intersections, a characteristic spacing of 100 μm distinguished three distinct cellular responses: anchoring, turning, and bridging. The probability of a cell altering its preexisting migration path depended on its ability to extend laterally and reach adjacent fibers, which was constrained by the upper limit of the cell body’s minor axis. This study elucidated the unique role of the electrospun fiber topography in guiding cellular decision-making in complex microenvironments, provided important insights into topography-triggered cell migration, and highlighted the practical significance of material-guided strategies in tissue engineering. Full article

We developed biomimetic full-thickness artificial skin using stromal vascular fraction (SVF) cells and autologous keratinocytes for the dermal and epidermal layers of skin, respectively. Full-thickness artificial skin scaffolds were fabricated using 4% porcine collagen and/or elastin in a low-temperature three-dimensional printer. Two types of scaffolds with collagen-to-elastin ratios of 100:0 and 100:4 were printed and compared. The scaffolds were analyzed for collagenase degradation, tensile strength, and structural features using scanning electron microscopy. By 24 h, the collagen-only scaffolds showed gradual degradation, and the collagen-elastin scaffolds retained the highest structural integrity but were not degraded. In the tensile strength tests, the collagen-only scaffolds exhibited a tensile strength of 2.2 N, while the collagen-elastin scaffolds showed a tensile strength of 4.2 N. Cell viability tests for keratinocytes displayed an initial viability of 89.32 ± 3.01% on day 1, which gradually increased to 97.22 ± 4.99% by day 7. Similarly, SVF cells exhibited a viability of 93.68 ± 1.82% on day 1, which slightly improved to 97.12 ± 1.64% on day 7. This study presents a novel strategy for full-thickness artificial skin development, combining SVF and keratinocytes with an optimized single collagen scaffold and a gradient pore-density structure. Full article

Radiation therapy, a highly effective cancer treatment that targets cancer cells, may produce challenging side effects, including radiation-induced skin tissue injuries. The wound healing process involves complex cellular responses, with key phases including hemostasis, inflammation, proliferation, and remodeling. However, radiation-induced injuries disrupt this process, resulting in delayed healing, excessive scarring, and compromised tissue integrity. This review explores innovative approaches related to wound healing in post-radiotherapy defects, focusing on the integration of adipose-derived stem cells (ADSCs) in protein/polysaccharide bioengineered scaffolds. Such scaffolds, like hydrogels, sponges, or 3D-printed/bioprinted materials, provide a biocompatible and biomimetic environment that supports cell-to-cell and cell-to-matrix interactions. Various proteins and polysaccharides are discussed for beneficial properties and limitations, and their compatibility with ADSCs in wound healing applications. The potential of ADSCs-polymeric scaffold combinations in radiation-induced wound healing is investigated, alongside the mechanisms of cell proliferation, inflammation reduction, angiogenesis promotion, collagen formation, integrin binding, growth factor signaling, and activation of signaling pathways. New strategies to improve the therapeutic efficacy of ADSCs by integration in adaptive polymeric materials and designed scaffolds are highlighted, providing solutions for radiation-induced wounded skin, personalized care, faster tissue regeneration, and, ultimately, enhanced quality of the patients’ lives. Full article

Human adipose stem cells (ASCs) are multipotent cells expressing mesenchymal stem cell (MSC) markers that are capable of multilineage differentiation and secretion of bioactive factors. Their “homing” to injured tissues is mediated by chemokines, cytokines, adhesion molecules, and signaling pathways. Enhancing ASC homing is critical for improving regenerative therapies. Strategies include boosting chemotactic signaling, modulating immune responses to create a supportive environment, preconditioning ASCs with hypoxia or mechanical stimuli, co-culturing with supportive cells, applying surface modifications or genetic engineering, and using biomaterials to promote ASC recruitment, retention, and integration at injury sites. Scaffolds provide structural support and a biomimetic environment for ASC-based tissue regeneration. Natural scaffolds promote adhesion and differentiation but have mechanical limitations, while synthetic scaffolds offer tunable properties and controlled degradation. Functionalization with bioactive molecules improves the regenerative outcomes of different tissue types. Ceramic-based scaffolds, due to their strength and bioactivity, are ideal for bone healing. Composite scaffolds, combining polymers, ceramics, or metals, further optimize mechanical and biological properties, supporting personalized regenerative therapies. This review integrates concepts from cell biology, biomaterials science, and regenerative medicine to offer a comprehensive understanding of ASC homing and its impact on tissue engineering and clinical applications. Full article

The increasing incidence of osteoporotic fractures determines ongoing research on new methods and strategies for improving the difficult healing process of this type of fracture. Osteoporotic patients suffer from the intense side effects of accustomed drug treatment and its systemic distribution in the body. To overcome these drawbacks, besides searching for new drugs, 3D-printed scaffolds and drug delivery systems have started to be increasingly seen as the main strategy employed against osteoporosis. Three-dimensionally printed scaffolds can be tailored in intricate designs and make use of nanoscale topographical and biochemical cues able to enhance bone tissue regeneration. Research regarding drug delivery systems is exploring bold new ways of targeting bone tissue, making use of designs involving nanoparticles and intricate encapsulation and support methods. The local administration of treatment with the help of a scaffold-based drug delivery system looks like the best option through its use of the advantages of both structures. Biomimetic systems are considered the future norm in the field, while stimuli-responsiveness opens the door for the next level of efficiency, patient compliance, and a drastic reduction in side effects. The successful approval of these products still requires numerous challenges throughout the development and regulatory processes, but the interest and effort in this direction are high. This review explored various strategies for managing osteoporosis, emphasizing the use of scaffolds for targeted drug delivery to bone tissue. Instead of covering the whole subject, we focused on the most important aspects, with the intention to provide an up-to-date and useful introduction to the management of osteoporosis. Full article

Bone repair and regeneration following an injury still present challenges worldwide. Three-dimensional (3D) scaffolds made from various materials are used for bone tissue engineering (BTE) applications. Polymers, minerals and nanotechnology are now being used in combination to achieve specific goals for BTE, including the delivery of antimicrobials through the scaffolds to prevent post-surgical infection. While several materials are utilised for BTE, natural polymers present a unique set of materials that can be manipulated to formulate scaffolds for BTE applications. They have been found to demonstrate higher biocompatibility, biodegradability and lower toxicity. Some even naturally mimic the bone microarchitecture, providing inherent structural support for BTE. Natural polymers may be simply classified as those from plant and animal sources. From both sources, there are different types of proteins, polysaccharides and other specialised materials that are already in use for research in BTE. Interestingly, these have the potential to revolutionise the field of BTE with a sustainable approach. In this review, we first discuss the different natural polymers used in BTE from plant sources, followed by animal sources. We then explore novel materials that are aimed at sustainable approaches, focusing on innovation from the last decade. In these sections, we outline studies of these materials with different types of bone cells, including bone marrow mesenchymal stromal cells (MSCs), which are the progenitors of bone. We finally outline the limitations, conclusions and future directions from our perspective in this dynamic field of polymers in BTE. With this review, we hope to bring together the updated existing knowledge and the potential future of innovation and sustainability in natural polymers for biomimetic BTE applications for fellow scientists, researchers and surgeons in the field. Full article

Few design methods exist that provide clearly structured, visually intuitive, and easily monitored scaffolding for navigating the considerable complexity of biomimetic processes. To this end, we present a holistic biomimicry process framework informed by design abstraction models that clarifies core skills involved and how they combine to form essential practices, such as biology-to-design and challenge-to-biology. The structure–function and conditions-conducive-to-life perspectives are facilitated, ensuring support for sustainability considerations. We pair this framework with two process tools that make biomimicry design moves explicit for learners, educators, and practitioners. We share examples of the use of these tools from an upper-level undergraduate engineering course in biomimicry. Our observations indicate that the framework and tools support process acquisition, design iteration, knowledge transfer, and sustainability integration in biomimicry education and practice by enabling common design behaviors such as variation, iteration, debugging, and reflection. Full article

Three-dimensional (3D) cell culture models are widely used to provide a more physiologically relevant microenvironment in which to host and study desired cell types. These models vary in complexity and cost, ranging from simple and inexpensive to highly sophisticated and costly systems. In this study, we introduce a novel translucent multi-compartmentalized stacked multilayered nanocellulose scaffold and describe its fabrication, characterization, and potential application for co-culturing multiple cell types. The scaffold consists of bacterial nanocellulose (BNC) layers separated by interlayers of a lower density of nanocellulose fibers. Using this system, we co-cultured the MDA-MB-231 cell line with two tumor-associated cell types, namely BC-CAFs and M2 macrophages, to simulate the tumor microenvironment (TME). Cells remained viable and metabolically active for up to 15 days. Confocal microscopy showed no signs of cell invasion. However, BC-CAFs and MDA-MB-231 cells were frequently observed within the same layer. The expression of breast cancer-related genes was analyzed to assess the downstream functionality of the cells. We found that the E-cadherin expression was 20% lower in cancer cells co-cultured in the multi-compartmentalized scaffold than in those cultured in 2D plates. Since E-cadherin plays a critical role in preventing the initial dissociation of epithelial cells from the primary tumor mass and is often downregulated in the tumor microenvironment in vivo, this finding suggests that our scaffold more effectively recapitulates the complexity of a tumor microenvironment. Full article

Cartilage tissue engineering (CTE) is an advancing field focused on developing biomimetic scaffolds to overcome cartilage’s inherently limited self-repair capacity. Smart hydrogels (SHs) have gained prominence among the various scaffold materials due to their ability to modulate cellular behavior through tunable mechanical and biochemical properties. These hydrogels respond dynamically to external stimuli, offering precise control over biological processes and facilitating targeted tissue regeneration. Recent advances in fabrication technologies have enabled the design of SHs with sophisticated architecture, improved mechanical strength, and enhanced biointegration. Key features such as injectability, controlled biodegradability, and stimulus-dependent release of biomolecules make them particularly suitable for regenerative applications. The incorporation of nanoparticles further improves mechanical performance and delivery capability. In addition, shape memory and self-healing properties contribute to the scaffolds’ resilience and adaptability in dynamic physiological environments. An emerging innovation in this area is integrating artificial intelligence (AI) and omics-based approaches that enable high-resolution profiling of cellular responses to engineered hydrogels. These data-driven tools support the rational design and optimization of hydrogel systems and allow the development of more effective and personalized scaffolds. The convergence of smart hydrogel technologies with omics insights represents a transformative step in regenerative medicine and offers promising strategies for restoring cartilage function. Full article