Search Results (662)

Background: The implant–abutment joint is important for the long-term marginal tissue integrity in terms of biomimetic design that replicates the natural dentition under mastication forces. This study aimed to evaluate conical implant–abutment joints coupled at different tightening torque values through a mechanical fatigue test. Methods: Eighty conic implants (Ø: 3.8 mm L: 10 mm) with a 6° cone morse joint were embedded in resin blocks with an inclination of 30° ± 2°. The samples were divided into 8 groups (4 Test and 4 Control). The implant–abutment joints were coupled with different tightening torques: 25 Ncm (Group I), 30 Ncm (Group II), 35 Ncm (Group III) and 40 Ncm (Group IV). An in vitro cyclic loading test (1 × 10⁴ loads) was performed for 4 Test groups, while 4 Control groups did not receive any forces. All the samples were assessed with Scanning Electron Microscopy to compare the microfractures and microgaps on flexion and extension points. Results: Microscopy observation results showed significant differences among torque groups. We found that 30 Ncm had the best stability with less microgap. Conclusions: Tightening torque plays an important role in the distortion of the cone morse joint under mechanical forces. However, further studies should be conducted to validate the results using different implant–abutment joints for comparison. Full article

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

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

This comprehensive review explores the expansive design space of network architectures and their significant impact on the mechanical and viscoelastic properties of hydrogel systems. By examining the intricate relationships between molecular structure, network connectivity, and resulting bulk properties, we provide critical insights into rational design strategies for tailoring hydrogel mechanics for specific applications. Recent advances in sequence-defined crosslinkers, dynamic covalent chemistries, and biomimetic approaches have significantly expanded the toolbox for creating hydrogels with precisely controlled viscoelasticity, stiffness, and stress relaxation behavior—properties that are crucial for biomedical applications, particularly in tissue engineering and regenerative medicine. 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

Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering of the pore pattern. In this context, we propose the fabrication of a transwell-like device pursued by combining the proton beam writing (PBW) technique with wet etching onto thin layers of polydimethylsiloxane (PDMS). The resulting transwell-like device incorporates a PDMS membrane with finely controllable pore patterning that was used to study the arrangement and migration behavior of HCMEC/D3 cells, a well-established human brain microvascular endothelial cell model widely used to study vascular maturation in the brain. A comparison between commercial polycarbonate membranes and the PBW-holed membranes highlights the impact of the ordering of the pattern and porosity on cellular growth, self-organization, and transmigration by combining fluorescent microscopy and advanced digital processing. Endothelial cells were found to exhibit distinctive clustering, alignment, and migratory behavior close to the pores of the designed PBW-holed membrane. This is indicative of activation patterns associated with cytoskeletal remodeling, a critical element in the angiogenic process. This study stands up as a novel approach toward the development of more biomimetic barrier models (such as organ-on-chips). 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

The intervertebral disc, an anatomical compartment interposed between vertebral bodies, plays a key role in spine flexibility and compression loading. It comprises three tissues: the nucleus pulposus, the annulus fibrosus, and the end plates. Degeneration-related changes in the extracellular matrix of the nucleus pulposus upon ageing or pathological conditions prompted the present investigation into the impact of proteoglycan reduction, the main constituent of the healthy nucleus pulposus, on its physicochemical properties and cellular phenotypical changes. To mimic the native extracellular matrix, three-dimensional NP-mimicking constructs were developed using a biomimetic hydrogel composed of collagen type I, collagen type II, and proteoglycans. This system was fabricated using a bottom-up approach, employing highly pure monomeric collagen types I and II, which were induced to form a reconstituted fibrillar structure closely resembling the natural NP microenvironment. A comprehensive physicochemical characterization was conducted at varying proteoglycan percentages using scanning electron microscopy (SEM), FTIR, rheological tests, and water retention property analysis. The effect of microenvironment changes on the phenotype of nucleus pulposus cells was studied by their encapsulation within the various collagen–proteoglycan hydrogels. The morphological and immunochemistry analysis of the cells was performed to study the cell–matrix adhesion pathways and the expression of the cellular regulator hypoxia-inducible factor 1 alpha. These were linked to the analysis of the synthesis of healthy or pathological extracellular matrix components. The findings reveal that the reduction in proteoglycan content in the nucleus pulposus tissue triggers a pathological pathway, impairing the rheological and water retention properties. Consequently, the cell phenotypes are altered, inducing the synthesis of collagen type I rather than securing the natural physiological remodelling process by the synthesis of collagen type II and proteoglycans. Identifying the proteoglycan content threshold that triggers these pathological phenotypical changes could provide new diagnostic markers and early therapeutic strategies for intervertebral disc degeneration. Full article

Medical hydrogels represent a promising solution for the treatment of corneal diseases and trauma, offering potential to address the shortage of donor corneas. To meet the functional requirements of artificial corneas in tissue engineering, it is crucial to fabricate biomimetic structures with high optical transparency using 3D printing techniques. As fiber alignment during the printing process has a pronounced impact on light transmittance, precise control of the printing parameters is essential. This study focuses on the experimental optimization of 3D printing conditions for hydrogel materials to improve their physical properties, particularly optical clarity, thereby enhancing their suitability for artificial corneal applications. Collagen derived from bovine Achilles tendons was chosen due to its excellent printability. A series of controlled experiments were conducted to systematically investigate the influence of key process parameters on hydrogel transparency. The findings enabled the identification of an optimized parameter set that significantly improved the optical properties of the 3D-printed biomimetic corneal stroma. Additionally, cell seeding and culture assays confirmed the favorable biocompatibility of the developed material. 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

The results of radiotherapy in patients with primary malignant brain tumors are extremely dissatisfactory: the overall survival after a diagnosis of glioblastoma is typically less than three years. The development of spatially fractionated radiotherapy techniques could help to improve this bleak prognosis. In order to develop technical equipment and organ-specific therapy plans, dosimetry studies as well as radiobiology studies are conducted. Although perfect spheres are considered optimal phantoms by physicists, this does not reflect the wide variety of head sizes and shapes in our patient community. Depth from surface and X-ray dose absorption by tissue between dose entry point and target, two key parameters in medical physics planning, are largely determined by the shape and thickness of the skull bone. We have, therefore, designed and produced a biomimetic tool to correlate measured technical dose and biological response in human cancer cells: a brain phantom, produced from tissue-equivalent materials. In a first pilot study, utilizing our phantom to correlate technical dose measurements and metabolic response to radiation in human cancer cell lines, we demonstrate why an anthropomorphic phantom is preferable over a simple spheroid phantom. Full article