Search Results (881)

This first part of a two-part review examines how Computed Tomography(CT)-based, additively manufactured (AM) porous implants are used to reconstruct large segmental defects of the femur and tibia. We focus on lightweight patient-specific lattice implants, architected cages, and modular porous constructs that incorporate engineered porosity into the load-bearing structure and are deployed with plate-, nail-, or external-fixator-based stabilization. We show how defects are described and classified by size, morphology, and anatomical subsegment; how these descriptors influence fixation choice and the resulting mechanical environment; and where along the femur and tibia porous implants have been applied in clinical and preclinical settings. Across the literature, outcomes appear to depend most strongly on defect morphology and local biology, while fixation feasibility and construct behavior vary by subregional anatomy. Most reported constructs use Ti6Al4V porous architectures intended to share load with fixation, reduce stress shielding, and provide a regenerative space for graft and tissue ingrowth. Finite element analyses (FEA) and bench-top studies consistently indicate that lattice architecture, relative density (RD), and fixation concept jointly control stiffness, micromotion, and fatigue-sensitive regions, whereas early animal and human reports describe promising incorporation and functional recovery in selected cases. However, defect descriptors, fixation reporting, boundary conditions, and outcome metrics remain diverse, and explicit quantitative validation of simulations against mechanical or in vivo measurements is uncommon. Most published work relies on simulation and bench testing, with limited reporting of biological endpoints, leaving a validation gap that prevents direct translation. We emphasize the need for standardized defect and fixation descriptors, harmonized mechanical and modeling protocols, and defect-centered datasets that integrate anatomy, mechanics, and longitudinal outcomes. Across the 27 included studies (may be counted in more than one group), simulation and mechanical testing are reported in 19/27 (70%) and 15/27 (56%), respectively, while in vivo studies (preclinical or clinical) account for 9/27 (33%), highlighting a validation gap that limits translation. Part 2 (under review); of these two series review paper; Patient-Specific Lattice Implants for Segmental Femoral and Tibial Reconstruction (Part 2): CT-Based Personalization, Design Workflows, and Validation-A Review; extends this work by detailing CT-to-implant workflows, lattice design strategies, and methodological validation. Full article

The tendon-to-bone enthesis is a multiphasic structure with four structurally continuous and compositionally distinct regions: tendon, uncalcified fibrocartilage, calcified fibrocartilage and bone. Our study aimed to develop 3D scaffold-free in vitro spheroids and macro-tissues of the enthesis for applications as experimental tools to understand the development and repair of enthesis injury. This study hypothesises that integrating tendon and bone cell spheroids with bone marrow mesenchymal stem cell spheroids will facilitate the production of a fibrocartilaginous interface. 3D Spheroids: The biphasic (tendon–bone) and triphasic co-culture (tendon–stem cell–bone) of spheroids in growth media and chondrogenic media were investigated to establish fusion kinetics, and the cellular and ECM components produced via histology and immunohistochemistry. Complete fusion between spheroids occurred within 6-to-8 days in biphasic co-culture, and 15-to-20 days in triphasic co-culture. Compared to biphasic, the triphasic co-culture in chondrogenic media showed a continuous interface connecting the tendon and bone regions. The presence of collagen I, sulphated proteoglycans and collagen type II in the interface region of triphasic co-culture indicates fibrochondrogenic differentiation. 3D macro-tissues: The modular tissue engineering strategy was used in this study to produce enthesis macro-tissues using spheroids as building blocks. Spheroids were bio-assembled in the triphasic manner (12 tendon spheroids, 12 stem cell spheroids and 8 bone spheroids) in the custom-designed and 3D-printed temporary supports (Formlabs Clear Resin^®) using a customised spheroid bio-assembly system. The fusion of spheroids occurred by day 8 after bio-assembly, and they were removed from temporary supports and cultured in scaffold-free conditions. Although the bio-assembly methodology was successful in producing fused scaffold-free macro-tissues, the histological analysis revealed the presence of an extensive necrotic core due to the large-sized constructs. To conclude, the findings support the hypothesis that a triphasic co-culture has the potential to produce a structurally continuous fibrocartilaginous interface but requires further optimisation to produce macro-tissues with anatomical morphologies and reduced necrotic cores. Full article

Extrusion-based bioprinting is widely used for fabricating cell-laden constructs; however, its success is highly dependent on the rheological and biological performance of the bioink. Natural polysaccharide gums have emerged as promising bioink components due to their biocompatibility and tunable properties. Among them, tragacanth gum (TG), a complex anionic heteropolysaccharide composed of tragacanthin and bassorin fractions, has gained increasing attention for extrusion bioprinting applications. TG exhibits pronounced shear-thinning behavior, high water uptake, and spontaneous gel-forming ability, which collectively enhance the printability, shape fidelity, and structural stability of bioinks. This review critically summarizes recent advances in TG-based hydrogels and bioinks, with emphasis on their molecular characteristics, rheological and physicochemical properties, and biological performance in extrusion bioprinting systems. The role of TG as a functional component in composite bioinks, particularly in improving mechanical integrity, extrusion consistency, and cytocompatibility, is discussed. Finally, current challenges and future research directions are highlighted to support the development and clinical translation of TG-based bioinks for tissue engineering applications. Full article

The development of photocurable hydrogel biomaterial inks with suitable rheology, low cytotoxicity, and tuneable mechanical properties is essential for reliable biofabrication. This study aimed to formulate PEGDA–gelatine–collagen inks using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator. Rheological characterisation and flow-model fitting were performed, mechanical stiffness modulation under different light intensities was evaluated, complex structures were printed using direct extrusion and FRESH methodologies, and PEGDA/LAP extractables were quantified by NMR after controlled washing procedures. In vitro assays assessed cell viability and proliferation on the resulting scaffolds. The Herschel–Bulkley model best described the flow behaviour across formulations; while viscoelastic measurements showed that increasing light intensity progressively enhanced hydrogel stiffness, enabling fine control over final mechanical properties. NMR analysis showed that washing removed a substantial fraction of residual LAP, in agreement with the biological findings: fibroblasts failed to survive on unwashed scaffolds but exhibited robust proliferation and recovered their characteristic elongated morphology on washed constructs. Among all inks, PeGeCol_10_2 provided the best combination of shear-thinning behaviour, structural integrity, low residual photoinitiator, and tuneable mechanics. Using this formulation, we successfully printed large anatomical models with high fidelity and excellent handling properties, underscoring its potential for soft-tissue prosthetics and broader tissue-engineering applications. Full article

The regeneration of bone and the repair of large segmental bone defects represent critical challenges in regenerative medicine. Natural bone tissue is an anisotropic material characterized by an intricate gradient distribution in structure, mechanical properties, and biochemical composition; this multi-dimensional heterogeneity is crucial for maintaining its physiological functions and guiding regeneration. Although tissue engineering scaffolds have demonstrated significant potential in the treatment of bone defects, homogeneous or single-gradient scaffolds often struggle to precisely recapitulate the high degree of heterogeneity and anisotropy of natural bone from the macroscopic to the microscopic level, thereby limiting their capability in repairing complex bone defects. In recent years, biomimetic gradient scaffolds—particularly those employing multi-gradient synergistic designs that integrate physical structure, biochemical composition, and mechanical properties—have emerged as a research frontier in this field due to their ability to accurately mimic the natural bone microenvironment and regulate cellular behavior. This research aims to systematically review the latest research progress in gradient scaffolds for bone tissue engineering. First, gradient characteristics of biomimetic gradient bone scaffolds are summarized; second, the design strategies for gradient scaffolds are discussed in depth, with a focus on the applications and advantages of advanced fabrication techniques, such as additive manufacturing, in constructing multi-dimensional gradient structures; finally, based on current research findings, the emerging development trends and future research directions of biomimetic gradient bone scaffolds are outlined to provide a reference for innovative breakthroughs in the field of bone tissue engineering. Full article

Additive manufacturing of hydrogel-based scaffolds requires concurrent control of material rheology and extrusion dynamics, especially in multi-material architectures. In this work, we develop a modular multi-material extrusion-based 3D-printing platform that combines a filament-fed extruder for thermoplastic polymers with a piston-driven extruder for viscous gel inks, together with an empirical calibration procedure for gel dosing. The calibration algorithm optimizes the pre-extrusion and retraction displacement (E_Pr/R) based on stepwise extrusion experiments and reduces the discrepancy between theoretical and measured deposited mass for shear-thinning alginate gels to below the prescribed tolerance. The calibrated system is then used to fabricate two representative hybrid constructs: partially crosslinked sodium alginate scaffolds with an internal hollow channel supported by a removable polycaprolactone framework, and self-supporting structures based on a sodium alginate–chitosan polyelectrolyte complex obtained by sequential co-extrusion. The resulting constructs remain mechanically stable after ionic crosslinking and solvent treatment and can subsequently be converted into highly porous scaffolds by freeze- or supercritical drying. The proposed combination of hardware architecture and extrusion calibration enables reproducible multi-material 3D printing of hydrogel–thermoplastic hybrid scaffolds and can be readily adapted to other gel-based inks for tissue engineering applications. Full article

A biomimetic cartilage scaffold featuring a continuous hydroxyapatite (HA) concentration gradient and a spatially curved architecture was developed using a dual-channel mixing extrusion-based 3D printing approach. By dynamically regulating the feeding rates of two bioinks during printing, a continuous HA gradient decreasing from the bottom to the top of the scaffold was precisely achieved, mimicking the compositional transition from the calcified to the non-calcified cartilage region in native articular cartilage. The integration of gradient material deposition with synchronized multi-axis motion enabled accurate fabrication of curved geometries with high structural fidelity. The printed scaffolds exhibited stable swelling and degradation behavior and showed improved compressive performance compared with step-gradient counterparts. Rheological analysis confirmed that the bioinks possessed suitable shear-thinning and recovery properties, ensuring printability and shape stability during extrusion. In vitro evaluations demonstrated good cytocompatibility, supporting bone marrow mesenchymal stem cell (BMSC) adhesion and proliferation. Chondrogenic assessment based on scaffold extracts indicated that the incorporation of HA and its gradient distribution did not inhibit cartilage-related extracellular matrix synthesis, confirming the biosafety of the composite hydrogel system. Overall, this study presents a controllable and versatile fabrication strategy for constructing curved, compositionally graded cartilage scaffolds, providing a promising platform for the development of biomimetic cartilage tissue engineering constructs. Full article

Spinal cord injury (SCI) remains one of the most formidable challenges in regenerative medicine, often resulting in permanent loss of motor, sensory, and autonomic function. Cell-based therapies offer a promising path toward repair by providing donor neurons and glia capable of integrating into host circuits, modulating the injury environment, and restoring function. Early studies employing fetal neural tissue and neural progenitor cells (NPCs) have demonstrated proof-of-principle for survival, differentiation, and synaptic integration. More recently, pluripotent stem cell (PSC)-derived donor populations and engineered constructs have expanded the therapeutic repertoire, enabling precise specification of interneuron subtypes, astrocytes, and oligodendrocytes tailored to the injured spinal cord. Advances in genetic engineering, including CRISPR-based editing, trophic factor overexpression, and immune-evasive modifications, are giving rise to next-generation donor cells with enhanced survival and controllable integration. At the same time, biomaterials, pharmacological agents, activity-based therapies, and neuromodulation strategies are being combined with transplantation to overcome barriers and promote long-term recovery. In this review, we summarize progress in designing and engineering donor cells and tissues for SCI repair, highlight how combination strategies are reshaping the therapeutic landscape, and outline opportunities for next-generation approaches. Together, these advances point toward a future in which tailored, multimodal cell-based therapies achieve consistent and durable restoration of spinal cord function. Full article

Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions can achieve >96% absorption across 250–2500 nm and photothermal efficiencies exceeding 98% under one-sun illumination (1000 W·m⁻², AM 1.5G). Next, we highlight advances in solar steam generation and desalination: floating photothermal receivers on carbonized wood or hydrogels reach >95% efficiency in solar-to-vapor conversion and >2 kg·m⁻²·h⁻¹ evaporation rates; three-dimensional architectures recapture diffuse flux and ambient heat; and full-spectrum nanofluids (LaB₆, Au colloids) extend photothermal harvesting into portable, scalable designs. We then survey photothermal-enhanced thermal energy storage: metal-oxide–paraffin composites, core–shell phase-change material (PCM) nanocapsules, and MXene– polyethylene glycol—PEG—aerogels deliver >85% solar charging efficiencies, reduce supercooling, and improve thermal conductivity. In biomedicine, gold nanoshells, nanorods, and transition-metal dichalcogenide (TMDC) nanosheets enable deep-tissue photothermal therapy (PTT) with imaging guidance, achieving >94% tumor ablation in preclinical and pilot clinical studies. Multifunctional constructs combine PTT with chemotherapy, immunotherapy, or gene regulation, yielding synergistic tumor eradication and durable immune responses. Finally, we explore emerging opto-thermal nanobiosystems—light-triggered gene silencing in microalgae and poly(N-isopropylacrylamide) (PNIPAM)–gold nanoparticle (AuNP) membranes for microfluidic photothermal filtration and control—demonstrating how nanoscale heating enables remote, reversible biological and fluidic functions. We conclude by discussing challenges in scalable nanoparticle synthesis, stability, and integration, and outline future directions: multicomponent high-entropy alloys, modular photothermal–PCM devices, and opto-thermal control in synthetic biology. These interdisciplinary innovations promise sustainable solutions for global energy, water, and healthcare demands. Full article

Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of USPs along with their applications in three-dimensional (3D) bioprinting. We first discuss how peptide sequence, terminal and side-chain modifications, and environmental triggers govern USPs’ self-assembly into nanofibers and 3D networks and how these supramolecular features translate into key rheological properties such as shear-thinning, rapid gelation, and mechanical tunability. We then survey reported applications in tissue engineering, wound healing, and organotypic models, as well as emerging ultra-short peptide-based systems for drug delivery, biosensing, and imaging, highlighting examples where printed constructs support cell viability, differentiation, and matrix deposition. Attention is given to hybrid and multi-material formulations in which USPs provide bioactivity while complementary components contribute structural robustness or additional functionality. Finally, this review outlines the main challenges that currently limit widespread adoption, including achieving high print fidelity with cytocompatible crosslinking, controlling batch-to-batch variability, and addressing the scalability, cost, and sustainability of peptide manufacturing. We conclude by discussing future opportunities such as AI-assisted peptide design, adaptive and multi-material bioprinting workflows, and greener synthetic routes, which together may accelerate the translation of ultra-short peptide-based bioinks from proof-of-concept studies to clinically and industrially relevant platforms. Full article

Tissue engineering is entering a new era, one defined not by passive scaffolds but by smart, adaptive biomaterials that can sense, think, and respond to their surroundings. These next-generation materials go beyond simply providing structure; they interact with cells and tissues in real time. Recent advances in mechanically responsive hydrogels and dynamic crosslinking have demonstrated how materials can adjust their stiffness, repair themselves, and transmit mechanical cues that directly influence cell behavior and tissue growth. Meanwhile, in vivo studies are demonstrating how engineered materials can harness the body’s own mechanical forces to activate natural repair programs without relying on growth factors or additional ligands, paving the way for minimally invasive, force-based therapies. The emergence of electroactive and conductive biomaterials has further expanded these capabilities, enabling two-way electrical communication with excitable tissues such as the heart and nerves, supporting more coordinated and mature tissue growth. Meanwhile, programmable bioinks and advanced bioprinting technologies now allow for precise spatial patterning of multiple materials and living cells. These printed constructs can adapt and regenerate after implantation, combining architectural stability with flexibility to respond to biological changes. This review brings together these cross-cutting advances, dynamic chemical design, mechanobiology-guided engineering, bioelectronic integration, and precision bio-fabrication to provide a comprehensive view of the path forward in this field. We discuss key challenges, including scalability, safety compliance, and real-time sensing validation, alongside emerging opportunities such as in situ stimulation, personalized electromechanical sites, and closed loop “living” implants. Taken together, these adaptive biomaterials represent a transformative step toward information-rich, self-aware scaffolds capable of guiding regeneration in patient-specific pathways, blurring the boundary between living tissue and engineered material. Full article

Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article

Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein conformation, which can be precisely regulated through processing and fabrication strategies. Recent advances in bioengineering have further expanded the capabilities of BMSF, enabling the development of biomaterials with engineered architectures, tailored microtopographies, and enhanced bioactivity. These technological developments have facilitated the design of scaffolds that more effectively guide tissue regeneration and enhance functional outcomes. Such constructs have demonstrated promising outcomes in the regeneration of bone, cartilage, vascular, neural, corneal, and skin tissues. This review summarises current progress while emphasising emerging trends that couple BMSF’s unique molecular features with immune-responsive design, instructive microarchitectures that guide cell behaviour, composite scaffold design, and functionalisation with bioactive molecules. BMSF has been positioned as a structurally adaptable and biologically instructive platform whose continued progression will depend on integrating advanced fabrication, mechanistic understanding, and translational standardisation. Full article

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO₂) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was employed to quantify manganese content. To assess siRNA stability within the system, samples were incubated with 50% fetal bovine serum (FBS) before agarose gel electrophoresis analysis. Additionally, cellular internalization by 4T1 cells and in vitro photothermal conversion efficiency of the formulation were evaluated. ICP-OES was further utilized to investigate the in vivo pharmacokinetics and tissue distribution of manganese. Animal model studies were conducted to assess the anti-breast cancer efficacy of PDA@Mn-siSur-c-NPs in combination with infrared irradiation. Results: The newly developed PDA@Mn-siSur-c-NPs demonstrated superior siRNA protection, reduced toxicity, and high photothermal conversion capacity. When combined with photothermal therapy (PTT), these nanoparticles exerted enhanced synergistic anti-tumor effects. Delivery of survivin siRNA resulted in a significant downregulation of survivin protein expression in tumor tissues. Moreover, magnetic resonance imaging (MRI) confirmed that the nanoparticles possess favorable imaging properties. Conclusions: This research demonstrates that the integration of PDA@Mn-siSur-c-NPs with PTT holds considerable therapeutic promise for improved breast cancer treatment. Full article

Biomimetic scaffolds are required in tissue engineering to provide structural support as well as promote cell adhesion, proliferation, and differentiation. Fibrous scaffolds composed of micro- and nanofibers replicate the architecture of the native extracellular matrix. Electrospinning is widely used for fabricating nanofibers; however, constructing fibrous scaffolds that integrate multiple fiber scales into a single structure is difficult. We addressed this issue by developing a fiber-spinning device using two pairs of counter-facing syringes that simultaneously produce micro- and nanofibers under different processing conditions. Poly(ε-caprolactone) solutions are ejected through needle-type nozzles via centrifugal force, and fiber diameter is controlled by adjusting the polymer concentration and nozzle diameter. We fabricated scaffolds with the proposed device, which exhibited a random three-dimensional fibrous network in which microfibers and nanofibers were homogeneously integrated. C2C12 myoblasts cultured on the composite scaffolds strongly adhered to the fibrous network, remained viable, and extended along the fibers to form multinucleated cells within the structure. The developed system produced composite micro/nanofiber scaffolds with tunable morphology and biocompatibility, providing a platform for fibrous tissue engineering applications. Full article