Search Results (2,283)

Mesoporous bioactive glasses (MBGs) represent a significant advancement in bioactive glass technology, combining the well-established osteoconductive and osteoinductive properties of traditional bioactive glasses with the structural precision provided by highly ordered mesoporosity. Their characteristic architecture, defined by uniform pores typically ranging from a few to several tens of nanometers and exceptionally high surface areas reaching several hundred m²/g, enables enhanced drug-loading capacity, controlled therapeutic ion release, and accelerated tissue regeneration. In this work, we emphasize how the synthesis of these materials is predominantly governed by structure-directing agents, which critically influence the pore size, mesophase ordering, surface area, and structural stability. Additionally, we discuss how compositional tailoring, particularly through therapeutic ion doping with elements such as Sr, Cu, Zn, or B, can impart osteogenic, angiogenic, antibacterial, or antioxidant functionalities. Moreover, we illustrate how these functionalities can be further expanded and enhanced by employing a comprehensive suite of characterization tools to establish robust correlations between synthesis parameters, mesostructural features, and biological performance. Improving the above functionalities enables the MBGs to exhibit exceptional versatility across biomedical applications, notably in bone tissue engineering (as hierarchical or composite scaffolds), controlled drug delivery (anticancer, antibiotic, and anti-inflammatory agents), wound healing, dental therapy, and bioactive implant coatings. Finally, we acknowledge that despite their broad potential, several associated challenges remain, including the synthesis scalability, batch-to-batch reproducibility, mechanical fragility of pure MBGs, and the complexity of predicting in vivo degradation and ion-release behaviors. We believe that emerging research directions, including eco-friendly synthesis routes, stimuli-responsive smart MBGs, multifunctional theranostic platforms, and patient-specific additive manufacturing, are poised to overcome current limitations and drive the next generation of MBG-based biomedical technologies. Full article

Soft-tissue management is critical for guided bone regeneration (GBR), yet conventional titanium meshes lack the ability to regionally regulate fibroblast behavior where opposite biological responses are needed. Here, we fabricated two femtosecond-laser patterned stripe topographies on titanium using a unidirectional scanning strategy with parameter tuning, generating LSFL with a periodicity of 820 ± 30 nm and micro-grooves with a periodicity of 4.7 ± 0.1 μm. Surface morphology and physicochemical properties were characterized by SEM/AFM, XPS, microhardness testing, and wettability measurements. Human gingival fibroblasts (HGF-1) were used to assess adhesion, cytoskeletal organization, spreading area, and proliferation (CCK-8). The submicron LSFL promoted robust fibroblast adhesion, aligned cytoskeletal organization, larger spreading areas, and higher proliferation, whereas the micro-groove surface markedly restricted spreading and was associated with poorer cytoskeletal organization and lower proliferation. Alternating patterned regions further demonstrated geometry-driven spatial selectivity, with preferential cell occupation on LSFL stripes. These findings support a fabrication-ready surface-engineering strategy to synchronize rapid soft-tissue sealing while restricting unwanted fibroblast advancement at defined regions, offering a promising route toward more predictable GBR outcomes. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Decellularization removes immunogenic intracellular components of fish tissues while keeping the extracellular matrix (dECM) structure, mechanical integrity, and bioactivity. Fish-derived dECM retains native bioactive components, exhibiting high biocompatibility, low immunogenicity, and biodegradability, while supporting cell adhesion, proliferation, and tissue regeneration. Due to its abundance, minimal ethical concerns, and low zoonotic risks, fish wastes are emerging as sustainable sources of dECM, offering an eco-friendly alternative to mammalian biomaterials. This review highlights advances in decellularizing fish wastes such as skin, scales, bones, viscera, and swim bladders from species including tilapia, tuna, milkfish, carp, goldfish, and sturgeon. Physical, chemical, biological, and hybrid decellularization methods are assessed for cell removal, ECM preservation, and mechanical performance. Recent advances in polymer-dECM composites, crosslinking, and 3D bioprinting have significantly improved scaffold performance, making fish-derived dECM applicable for healing of wounds, regeneration of bone and cartilage, and repair of soft tissues. Despite its potential, challenges remain in optimizing perfusion rates, temperature variations, and tissue-specific protocols, as well as developing eco-friendly decellularization techniques using biodegradable reagents. Future perspectives include expanding decellularized fish tissue sources, innovating bio-inks for 3D bioprinting, and refining tissue-specific processing methods to maximize the potential of fish-derived dECM in regenerative medicine and tissue engineering. Full article

Autogenous grafts remain the gold standard for repairing extensive maxillofacial bone defects, but their associated morbidity motivates the search for alternative strategies in tissue bioengineering. Deciduous dental pulp stem cells (DDPSCs) represent a promising cell source due to their accessibility, multipotency, and osteogenic potential, while nanostructured carbonated hydroxyapatite (cHA) microspheres exhibit biochemical similarity to bone mineral and favorable bioabsorption. This study investigated the osteogenic response induced by the association of DDPSCs with cHA in a rat calvaria critical-size defect model. DDPSCs were expanded, seeded onto cHA microspheres, and characterized in vitro prior to bilateral implantation in 12 Wistar rats, with each animal receiving cHA + DDPSC on the right defect and acellular cHA on the left. After 60 and 90 days, histological and histomorphometric analyses revealed new bone formation in both groups, predominantly from the defect margins toward the center. At 60 days, no significant difference in newly formed bone was observed between groups (p = 0.249). At 90 days, the DDPSC + cHA group demonstrated significantly greater bone formation compared with acellular cHA (median 40.70 vs. 11.10 histomorphometric points; p = 0.028) and significant reduction in connective tissue (p = 0.028). Complete scaffold resorption was observed in all DDPSC-treated defects at 90 days, whereas residual biomaterial persisted in the cHA group (p = 0.015), indicating progressive cHA resorption over time. These findings suggest that combining DDPSCs with cHA enhances bone regeneration and that this synthetic, bioabsorbable scaffold represents a promising strategy for future applications in bone tissue engineering. Full article

In this research, Fe-P scaffolds were successfully fabricated by the powder metallurgy method for the first time, using NaCl as the space holder for bone tissue engineering applications, with apparent porosities of approximately 70%. The Fe₃P powder was successfully synthesized by the mechanochemical method under an argon atmosphere using an initial mixture of Fe and P powders. The XRD patterns show that Fe₃P was obtained after sintering the milled powders at 1000 °C. Fe, Fe₃P, and Fe-50 wt% Fe₃P composite scaffolds and bulk pellets were prepared by sintering the milled powder at 1000 °C. Furthermore, the mechanical properties (compression strength) and bioactivity of the Fe-P scaffolds were determined. According to the compression test results, the composite scaffold showed higher compressive strength, lower fracture strain, and higher elastic modulus than the Fe and Fe₃P scaffolds, indicating that adding Fe₃P to Fe improves the mechanical properties. Moreover, among the scaffolds prepared by sintering at 1000 °C, the Fe scaffold exhibited the highest corrosion rate compared to the Fe₃P and composite samples, while the corrosion resistance of the composite sample was 3 times higher than that of the Fe sample. The ICP analysis showed that the amount of Fe released from the bulk pellets during soaking in PBS solution after four weeks was 3220 μg/dL, 4003 μg/dL, and 4774 μg/dL for the composite, Fe₃P, and Fe samples, respectively. The composite sample showed the highest cell viability, while the Fe sample had the lowest. The compressive strength (12.62 MPa) and fracture strain (5.98%) of the porous sintered composite scaffold at 1000 °C were within the range of trabecular bone, while the compressive strength of the composite sample was 17 times higher than that of the Fe sample. Furthermore, the MTS test showed that all the samples had good viability, while the composite sample had the best cell viability. The scaffolds were not cytotoxic. It can be concluded that the mechanical and biological properties of the composite sample were superior to those of the Fe and Fe₃P samples and that it may be a promising candidate for bone tissue engineering applications, especially for trabecular bone replacement. Full article

Acute and chronic kidney diseases remain significant challenges in regenerative medicine, with few therapies capable of reversing tissue injury or preventing progression. Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) are nanosized vesicles (30–150 nm) that have emerged as multifunctional nanotheranostic platforms, combining targeted therapeutic activity with imaging-enabled monitoring. In renal pathophysiology, BM-MSC-Exos exert anti-inflammatory, anti-fibrotic, angiogenic, and pro-regenerative effects. These actions are mediated by microRNAs, messenger RNAs, mitochondrial regulators, and bioactive proteins that modulate epithelial repair and immune responses. Recent bioengineering advances enable more precise BM-MSC-Exos design, including enrichment with synthetic RNAs or gene-editing components and membrane functionalization to enhance kidney tropism. In parallel, fluorescence, bioluminescence, and nanoparticle-based approaches support in vivo tracking. These tools allow real-time assessment of biodistribution and tubular uptake, strengthening evidence for target engagement. This review synthesizes current knowledge on BM-MSC-Exos in renal repair. We summarize contemporary strategies for cargo and surface engineering, outline imaging methodologies for in vivo tracking, and discuss how administration routes influence renal targeting. We also provide an updated overview of clinical trials evaluating exosomes as therapeutic agents or biomarkers in nephrology. Collectively, engineered BM-MSC-Exos represent a promising and increasingly sophisticated platform for precision-guided kidney therapy, supported by monitoring tools that facilitate preclinical evaluation of biodistribution and efficacy. Full article

As a novel theoretical and practical advantage, preclinical to clinical evidence, this systematic review of PRP, growth factors, and stable gastric pentadecapeptide BPC 157 efficacy in complex musculoskeletal and junctional injuries emphasizes the cytoprotection concept, healing to restore tissue integrity. Notably, the concept holds tendon, ligament, and muscle healing, in particular. Then, it holds their healing together as interconnected lesions. Consequently, this review presents the possibilities for cytoprotective therapies suited for tendon/ligament/muscle and recovery of osteotendinous, myotendinous, and the muscle-to-bone junction. The estimated key was the success of injury recovery amid each agent’s direct exogenous administration, alone or with a carrier, locally or systemically, without reliance on complex scaffolds, carriers, or tissue-engineering constructs. As reviewed, while with commonly acknowledged physiological significance, and acting throughout cytoprotection principles, growth factors (PDGF, TGF-β1, IGF-1, FGF, VEGF, BMPs) delivered locally with various carriers improve tendon, ligament, and muscle healing; however, some (PDGF, TGF-β1, IGF-1) may fail in muscle lesions, and all show limited or no efficacy in junctional healing. Contrarily, proposed as a cytoprotection mediator, BPC 157 acts alone with a full cytoprotection range, given systemically or locally. Moreover, without any carrier, BPC 157 acts alone, combining beneficial effects on tendon, ligament, and muscle injuries with osteotendinous, myotendinous, and muscle-to-bone healing. In rat studies, across systemic (intraperitoneal, intragastric, or drinking water) and local (cream) administration, BPC 157 consistently demonstrated efficacy, indicating considerable translational potential. Further clinical studies will strengthen cytoprotective therapy and, particularly, BPC 157 in complex musculoskeletal and junctional injuries. Full article

This study developed multifunctional chitosan–hydroxyapatite (CH–HAp) scaffolds incorporating cobalt ferrite (CoFe₂O₄, CFO) nanoparticles and carvacrol to combine bone regeneration potential with magnetic responsiveness and antimicrobial activity. Scaffolds containing 5 wt% CFO and 10–30 wt% carvacrol (free or Tween 80-emulsified) were fabricated via freeze-drying. The inclusion of CFO provided ferrimagnetic behavior, while carvacrol reduced chitosan crystallinity and increased scaffold porosity. Formulations with 30 wt% carvacrol demonstrated the strongest antimicrobial effect, showing inhibition halos against Staphylococcus aureus, Escherichia coli, Candida albicans, and Candida glabrata. The scaffold combining emulsified carvacrol and CFO exhibited a highly porous (≈90%) structure, preserved magnetic response, and mild cytotoxicity toward L929 fibroblasts, indicating cytocompatibility. The synergistic integration of CFO and carvacrol in a CH–HAp matrix yielded a multifunctional platform that simultaneously provides structural support, magnetic responsiveness, and antimicrobial performance, showing great promise for advanced bone tissue engineering applications. Full article

The achievements of regenerative medicine are based on methods of controlling stem cell division and differentiation. Electromagnetic fields stimulate cell differentiation by means of affecting calcium channels and cellular signaling. However, only a small part of the mechanisms underlying electromagnetic field effect on cells has been studied. The prospect of their use in tissue engineering as an addition or alternative to biochemical effects becomes clear in the course of numerous experiments. Electromagnetic stimulation enhances the effect of biochemical differentiation inducers and can cause the secretion of exosomes of special properties, which may serve as a therapeutic tool. For example, it has been shown that EMFs at 15 Hz and 2 mT increased the expression of chondrogenic differentiation markers SOX9 and COL2 in human bone-marrow MSCs by up to 3-fold (based on Parate et al.). Optimizing EMF parameters (e.g., 15–50 Hz, 1–2 mT) for specific cells and pathologies remains a key challenge of the studies in the field of tissue engineering. This review describes the electromagnetic field effect on the chondrogenic and osteogenic differentiation of MSCs of various origins, which is important for the musculoskeletal tissue recovery, as well as on inflammatory diseases in model animals. Full article

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

Oral administration of tocotrienol has poor systemic distribution due to poor selectivity by the α-tocopherol transfer protein at the liver. Local injection of tocotrienols with appropriate drug delivery systems is significant to ensure that the drug is delivered directly to the site of injury or fracture. This paper presents a tocotrienol-loaded gelatin hydrogel crosslinked with genipin for bone regeneration. This innovative method improves the incorporation and sustained delivery of tocotrienol while overcoming its incompatibility with hydrophilic biomaterials. It establishes a novel platform for targeted therapeutic applications in bone treatment. The cytotoxicity and physicochemical properties of tocotrienol were examined using the genipin-crosslinked gelatin hydrogel. A 10% tocotrienol nanoemulsion (TTE) was prepared using a sonicator and characterized with a zeta sizer and FTIR. A dose–response analysis was conducted to determine the appropriate tocotrienol concentration for hydrogel integration with gelatin (7% or 10% w/v) and crosslinked with genipin (0.1% or 0.3% w/v). The dose–response study’s tocotrienol nanoemulsion was added to gelatin before polymerization. With 141.9 nm particles and 0.150 PDI, the nanoemulsion was homogeneous and stable. The 1% tocotrienol nanoemulsion was chosen due to its viability. Formulations 1% TTE_0.1% GNP_7% GEL and 1%TTE_0.3% GNP_7% GEL had superior physicochemical properties compared to other groups. The 1% TTE_0.3% GNP_7% GEL had outstanding hydrophilicity, low weight loss, and a suitable swelling ratio for bone application. SEM scans of the surface and cross-section showed that 1% TTE_0. 3% GNP_7% GEL had interconnected pores with an optimal average pore size of 292 ± 37 μm. Adding tocotrienol to the gelatin hydrogel matrix did not affect FTIR, XRD, or EDX. In vitro cytotoxicity studies indicated >90% cell viability of hFOB 1.19 cells cultured on 1% TTE_0.1% GNP_7% GEL and 1% TTE_0.3% GNP_7% GEL (105 ± 4.36% and 95.36 ± 9.78%). Combining tocotrienol with a genipin-crosslinked gelatin hydrogel demonstrated superior physicochemical properties and no in vitro toxicity. Full article

This experimental review discusses evolutionarily approved, naturally pre-designed skeletal architectures of marine keratosan sponges in the form of 3D scaffolds, which have garnered increasing interest in the fields of structural and functional biomimetics as well as in tissue engineering. It has been demonstrated that these renewable, ready-to-use natural scaffolds can undergo further modifications through specialized treatments such as metallization and carbonization, enabling the creation of functional biomaterials while maintaining the species-specific hierarchical 3D structure. The study presented remarkable findings, including the demonstration of the unique shape-memory behavior of these scaffolds even after two months of exposure to high mechanical pressure at temperatures exceeding 100 °C. Additionally, the cytocompatibility and biological performance of natural and carbonized (1200 °C) spongin scaffolds, derived from selected bath sponges, were comparatively investigated with respect to growth and proliferation of human MG-63 osteoblastic cells. Understanding whether carbonization universally enhances osteogenic capabilities or selectively amplifies the inherent architectural advantages remains to be critical for the rational design of sponge-derived scaffolds in bone and structural tissue engineering applications. Full article

Objectives: This prospective cohort study aimed to evaluate the accuracy and precision of static computer-guided, flapless implant surgery in partially edentulous patients, comparing the virtually planned and clinically achieved implant positions. Materials and Methods: From 2017 to 2022, 40 patients (20 males and 20 females) received a total of 129 implants across 59 partial rehabilitations, with 62 implants placed in the maxilla and 67 in the mandible. All interventions were performed by a single experienced operator using dental-supported stereolithographic guides and a flapless protocol. The discrepancy between planned and actual implant positions was measured using reverse engineering software, assessing linear deviations at the implant Platform (coronal) and apex, as well as angular deviations. Subgroup analyses were conducted based on the jaw (maxilla vs. mandible) and the type of surgical guide support (Kennedy classes I–IV). Results: The mean linear deviation was 1.16 ± 0.58 mm at the apex and 0.80 ± 0.41 mm at the implant Platform (coronal). The mean angular deviation was 3.23° ± 1.86°. Slightly higher deviations were observed in the mandible than in the maxilla. Group-wise analysis showed minor variations depending on the type of guide support. Conclusions: Static computer-guided surgery demonstrated measurable linear and angular deviations between planned and achieved implant positions. These discrepancies should be considered during treatment planning, especially in narrow ridges or Class I configurations. Full article