Search Results (168)

Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function. Full article

In vitro chondrocyte expansion is key to all tissue engineering (TE) strategies using adult differentiated articular chondrocytes. Unfortunately, high proliferation rates in vitro can cause a progressive loss of chondrocyte phenotype (dedifferentiation) during culture passages. This can impair the quality of newly formed tissue after implantation because dedifferentiated chondrocytes mainly produce fibrocartilage, which hinders successful cartilage repair. Freshly isolated chondrocytes from equine articular cartilage were grown as a primary culture on tissue culture dishes and on 2D chitosan or chitosan/hyaluronic acid films. To evaluate chondrocyte differentiation during in vitro expansion, morphological observations, gene expression of chondrocyte phenotype markers, and LC-MS/MS shotgun proteomics were performed. All types of 2D cultures showed significantly reduced differentiation compared with freshly isolated cells, but chondrocytes grown on biomaterials maintained a rounded morphology and the gene expression of differentiation markers. Interestingly, pairwise proteomics comparison revealed a remarkable number of differentially expressed proteins, highlighting the different dynamics occurring in each experimental condition at the protein level. Based on novel insights into differentiation-dedifferentiation mechanisms, hypotheses were generated to explore new markers implicated in dedifferentiation and the role of biomaterials in this process by investigating the biological pathways associated with the reduced phenotype. Full article

The glial tube is a longitudinal structure predominantly composed of densely bundled, aligned astrocytes that projects from the subventricular zone (SVZ) to the olfactory bulb. Neural precursor cells (NPCs) generated in the SVZ migrate through this glial tube—referred to as the rostral migratory stream (RMS)—to replace olfactory bulb interneurons in the mammalian brain. RMS astrocytes have distinct morphological and functional characteristics. These characteristics facilitate the unique purpose of the RMS as an endogenous living scaffold directing NPC migration and maturation. However, the transcriptomic factors underlying these unique structure–function attributes versus standard stellate astrocytes have not been examined. We previously developed biofabrication techniques to create the first tissue-engineered rostral migratory stream (TE-RMS) that replicates key features of the glial tube in vivo. We have shown that TE-RMS astrocytes exhibit elongated nuclei, longitudinally aligned intermediate filaments, and enrichment of key functional proteins—cytoarchitectural and surface features characteristic of native RMS astrocytes. In the current study, we performed RNA-seq on TE-RMS astrocytes in comparison to planar astrocyte cultures to identify gene expression patterns that may underlie their profound morphological and functional differences. Remarkably, we found 4,008 differentially expressed genes in TE-RMS astrocytes, with 2076 downregulated (e.g., LOC690251 and ccn5) and 1932 upregulated (e.g., lrrc45 and cntn1) compared to planar astrocytes. Moreover, there were 256 downregulated and 91 upregulated genes with >3-fold change. We also conducted analyses of gene sets related to cytoskeleton and nuclear structure, revealing the greatest enrichment of actin-related components. Overall, the TE-RMS offers a platform to study the interplay between transcriptomic and cytoarchitectural dynamics in a unique astrocyte population. Full article

The demand for organ transplantation continues to rise worldwide, intensifying the gap between supply and demand and driving research in tissue engineering (TE). Bioprinting, particularly light-based vat photopolymerization (VP) methods such as digital light processing (DLP), has emerged as a promising strategy to fabricate complex, cell-compatible tissue constructs with high precision. In this study, we developed an open-source, bottom-up DLP bioprinter designed to provide a cost-effective and modular alternative to commercial systems. The device was built from commercially available components and custom-fabricated parts, with tolerance allocation and deviation analyses applied to ensure structural reliability. Mechanical and optical subsystems were modeled and validated, and the control architecture was implemented on the Arduino platform with a custom Python-based graphical interface. The system achieved a theoretical Z-axis resolution of 1 $\mathsf{\mu }$m and a vertical travel range of 50 mm, with accuracy and repeatability comparable to research-grade bioprinters. Initial printing trials using polyethylene glycol diacrylate (PEGDA) hydrogels demonstrated high-fidelity microfluidic constructs with adequate dimensional precision. Collectively, these results validate the functionality of the proposed system and highlight its potential as a flexible, precise, and cost-effective platform that is also easy to customize to advance the democratization of biofabrication in TE. Full article

The increasing demand for novel tissue engineering (TE) applications in bone tissue regeneration underscores the importance of exploring advanced manufacturing techniques and biomaterials for personalised treatment approaches. Three-dimensional printing (3DP) technology facilitates the development of implantable devices with intricate geometries, enabling patient-specific therapeutic solutions. Although Fused Filament Fabrication (FFF) and Direct Ink Writing (DIW) are widely utilised for fabricating bone-like implants, the need for multiple processing steps often prolongs the overall production time. In this study, a single-step melt-extrusion 3DP technique was performed to develop multi-material scaffolds including bioceramics, hydroxyapatite (HA), and β-tricalcium phosphate (TCP) in both their bioactive and calcined forms at 10% and 20% w/w, within polycaprolactone (PCL) matrices. Printing parameters were optimised, and physicochemical properties of all biomaterials and final forms were evaluated. Thermal degradation and surface morphology analyses assessed the consistency and distribution of the ceramics across the different formulations. The tensile testing of the scaffolds defined the impact of each ceramic type and wt% on scaffold flexibility performance, while in vitro cell studies determined the cytocompatibility efficiency. Hence, all 3D-printed PCL–ceramic composite scaffolds achieved structural integrity and physicochemical and thermal stability. The mechanical profile of extruded samples was relevant to the ceramic consistency, providing valuable insights for further mechanotransduction investigations. Notably, all materials showed high cell viability and proliferation, indicating strong biocompatibility. Therefore, this additive manufacturing (AM) process is a precise and fast approach for developing biomaterial-based scaffolds, with potential applications in surgical restoration and support of segmental bone defects. Full article

Stratum Corneum (SC) formation in the human epidermis requires lipid processing. Lipoxygenases (LOXs) such as 12R-Lipoxygenase (12R-LOX) and Epidermis-type lipoxygenase 3 (eLOX-3) contribute to this process. Mutations in their genes cause Autosomal Recessive Congenital Ichthyosis (ARCI) in patients. On the other hand, 12S-lipoxygenase (12S-LOX) is expressed in the human epidermis, but its role still remains to be clarified. The involvement of eLOX-3, 12R, and 12S-LOX in conditions or processes such as skin photodamage, wound healing, psoriasis, and atopic dermatitis is suggested but still remains unclear. In order to eventually gain a better understanding of the role of these LOXs in such processes, models of Tissue-Engineered Skins (TESs) with an impaired expression for the native form of either eLOX-3, 12R-LOX, or 12S-LOX were produced using CRISPR-Cas9(D10A) technology. All three models showed impaired keratinocyte differentiation and changes in the prevalence or the size of lipid droplets within the most superficial layers, thus reproducing features observed in ARCI and supporting a role for 12S-LOX in SC formation. Since eLOX-3 and 12R-LOX depleted TES’s reproduced features observed in ARCI, such models can be considered as reliable tools for the functional studies of these LOXs in the human epidermis. Full article

Cartilage tissue engineering aims to restore damaged cartilage using biomaterials, cells, and/or biological cues to support cell growth and tissue repair. Although in the past decades scientific advances have moved the field forward, their translation to a clinical setting is still hampered. One major hurdle to take is to reduce process variability to ensure a predictable biological outcome. Using enabling technologies such as bioprinting has shown the potential to improve process robustness. However, developing bioinks that balance printability with biological functionality remains a major challenge. This study presents the development and structure–property relationships of a novel gelatin-based hydrogel blend, GelMA/GelMA-AEMA, optimized for extrusion-based bioprinting (EBB) while maintaining the crucial biological properties of GelMA for tissue engineering applications. The novel GelMA/GelMA-AEMA blend demonstrated superior flowability and printability compared to GelMA, effectively addressing common 3D-printing defects such as filament shape inhomogeneity. A systematic rheological characterization revealed that the blend exhibits a softer, elastically dominated structure with improved compliance. The blend behaves as a yield-stress fluid with a strong shear-thinning degree, making it highly suitable for EBB. The superior flow properties of the blend are deemed to enhance bond slippage and stress-induced orientation of its more imperfect gel structure, resulting in greater macroscopic deformation and enhanced print fidelity. In addition, histological assessment of a 21-day in vitro study with iPSC-derived chondrocytes suggested that the blend is at least equally performant as GelMA in supporting matrix formation. Histological analysis shows similar matrix deposition profiles, whereas gene expression analysis and compression tests even have suggested superior characteristics for cartilage TE. This study emphasizes the central role of rheology in bioink development and provides foundations for future material development for EBB, with potential implications for cartilage tissue engineering. Full article

Tissue-engineered scaffolds, particularly composite scaffolds composed of polymers combined with ceramics, bioactive glasses, or nanomaterials, play a vital role in regenerative medicine by providing structural and biological support for tissue repair. As scaffold designs grow increasingly complex, the need for non-invasive imaging modalities capable of monitoring scaffold integration, degradation, and tissue regeneration in real-time has become critical. This review summarizes current non-invasive imaging techniques used to evaluate tissue-engineered constructs, including optical methods such as near-infrared fluorescence imaging (NIR), optical coherence tomography (OCT), and photoacoustic imaging (PAI); magnetic resonance imaging (MRI); X-ray-based approaches like computed tomography (CT); and ultrasound-based modalities. It discusses the unique advantages and limitations of each modality. Finally, the review identifies major challenges—including limited imaging depth, resolution trade-offs, and regulatory hurdles—and proposes future directions to enhance translational readiness and clinical adoption of imaging-guided tissue engineering (TE). Emerging prospects such as multimodal platforms and artificial intelligence (AI) assisted image analysis hold promise for improving precision, scalability, and clinical relevance in scaffold monitoring. Full article

In this work, the electrospinning technique was used to prepare novel polymeric composite fibers containing Te-doped bioactive glass powders. Bioactive glass powders containing tellurium (STe5 glass) were chosen as fillers for the composites, owing to their bioactive, antibacterial, and antioxidant properties. The biopolymer poly (ϵ-caprolactone) (PCL) and acetic acid (AA) were used as raw materials for the preparation of the polymeric matrix. FESEM analysis confirmed a good incorporation of the glass powders in the polymeric fibers, of up to 20% by weight. Wettability, mechanical, in vitro stability and preliminary antibacterial tests were also performed. The results showed that the treatment in AA did not affect the bioactivity of the glass powders, the presence of STe5 powders in PCL enhanced the wettability of the fibers, and mechanical properties improved by increasing the amount of STe5 powders, as well as the antibacterial effect. Therefore, the obtained materials appear promising for developing multifunctional composite materials for applications in tissue engineering. Full article

New stable three-dimensional hydrogels were obtained in an inert gas atmosphere in light in an aqueous dispersion of the main components: cod collagen, methyl methacrylate, polyethylene glycol, RbTe_1.5W_0.5O₆ complex oxide, and modifying additives. The analysis of the new hydrogels’ cytotoxicity using the MTT assay showed that the cytotoxicity of the sample extracts was observed in a number of examples, but was decreased with increasing dilution of the extracts. The decrease in cell viability at high concentrations of the extract is likely caused by a decrease in the number of specific components of the complete culture medium used to produce extracts. It is related to the well-known adsorption of medium proteins by the gel component, high-molecular compounds included in the matrix. The stimulating effect of the substances included in its composition was observed with a significant dilution of the extract, i.e., the proliferative activity of the cells increased. The extract of the hydrogel hydrolysate sample and all its dilutions did not show cytotoxicity in the MTT assay examples. It determines the prospect of its use on the wound surface, since hydrogel destruction occurs under the action of body enzymes. The new hydrogel is a promising material for creating wound coverings or scaffolds. Full article

Gelatin, a biocompatible and biodegradable polymer, has garnered considerable attention in tissue engineering (TE) due to its diverse applications enabled by its tunable physical properties. Among the various strategies employed for the fabrication of gelatin-based hydrogels, the use of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂) as a catalytic system has been highlighted as an effective tool for producing hydrogels with highly modifiable properties. Herein, we explore recent progress in the utilization of the HRP/H₂O₂ catalytic system for the creation of gelatin-based hydrogels, with an emphasis on TE applications. Particular attention has been given to the interplay between variations in the concentration equilibrium of HRP and H₂O₂ and the fine-tuning of gel properties tailored for various TE applications. Emerging trends, such as in situ gelation and hybrid bioinks, have also been examined through the lens of their prospective applications, extrapolating from the findings in cell cultures and animal models. A comprehensive review of two databases (Scopus and Web of Science) was conducted. The data extracted from each study included the materials used for each application, methods used for material preparation, cells used in the TE application, laboratory animals used, and whether computational/simulation techniques were implemented. The applications included both homopolymeric hydrogels, using only gelatin as the backbone, and copolymeric hydrogels, with ≥2 polymers. Full article

UV-cured methacrylated chitosan (MCHIT) hydrogels were achieved in the presence of silanised tellurium-doped silica bioactive glass (BG-Te-Sil) to produce an antimicrobial and osteoconductive scaffold for tissue engineering applications. Methacrylation of chitosan enabled efficient crosslinking, and the curing process was evaluated by means of Fourier-transform infrared spectroscopy (FTIR) and photorheology analyses. Compressive testing on crosslinked hydrogels showed that the silanised, bioactive, doped glass increased the hydrogel’s elastic modulus by up to 200% compared to unreinforced controls. Antibacterial assays against Staphylococcus aureus ATCC 43300 revealed a significant (p < 0.05) reduction in bacterial metabolic activity for hydrogels containing 50 wt% of the Te-doped bioactive glass. In vitro cytocompatibility with human bone-marrow mesenchymal stem cells demonstrated sustained viability and uniform distribution at 72 h (live/dead staining, AlamarBlue). Under H₂O₂-induced oxidative stress, reinforced hydrogels downregulated pro-inflammatory genes (TNF-α, IFN-γ, IL-1β, and PGES-2). These results suggest that the presence of the silanised bioactive glass can significantly enhance mechanical stability, antibacterial properties, and anti-inflammatory responses without affecting cytocompatibility, making these hydrogels promising for tissue engineering applications. Full article

The tooth and its supporting periodontium are essential structures of the oral cavity, frequently compromised by conditions such as dental defects, aries, and periodontal diseases, which, if poorly treated, often lead to tooth loss. These conditions, affecting billions of people worldwide, remain significant healthcare and socio-economic challenges. Regenerative dentistry has emerged as a possible therapeutic option, leveraging advances in tissue engineering (TE), stem cell biology, and biophysical stimulation. Oral tissue-derived mesenchymal stem/stromal cells (OMSCs) hold great potential for dental and periodontal regeneration. Electrical stimulation (ES), a biophysical cue known to regulate key cellular behaviors such as migration, proliferation, and differentiation, has gained increasing attention for enhancing the therapeutic capacities of OMSCs. This review explores the biological properties of OMSCs under ES, its role in regenerative dentistry, and recent breakthroughs in ES-based dental and periodontal TE strategies. Furthermore, the current challenges and future directions for translating these innovative approaches into clinical practice are discussed. Full article

Bacterial cellulose (BC) is a polysaccharide produced by Gram-positive and Gram-negative bacteria with a strictly aerobic metabolism, having a huge number of significant applications in the biomedical field. This study investigates the development of bacterial cellulose (BC)-based composite systems that incorporate cerium dioxide nanoparticles (CeO₂ NPs) used as antibacterial agents to enhance wound healing, particularly for burn treatments. The innovation of this study resides in the integration of CeO₂ NPs synthesized by using a precipitation method using both chemical and green reducing agents, ammonium hydroxide (NH₄OH) and turmeric extract (TE), in BC membranes composed of ultrathin nanofibers interwoven into a three-dimensional network appearing as a hydrogel mass. Characterization by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR) confirmed the effective deposition of this agent onto the BC matrix. Antibacterial activity tests against E. coli and B. subtilis indicated strong inhibition for the composites synthesized following these routes, particularly for the BC-CeO₂-TE-OH sample, processed by employing both precipitating agents. Cytotoxicity evaluations showed no inhibition of cell activity. Additionally, loading the composites with dexamethasone endowed them with analgesic release over 4 h, as observed through ultraviolet–visible spectroscopy (UV-Vis), while the FTIR spectra revealed a sustained drug presence post-release. These findings highlight BC-based films as promising candidates for advanced wound care and tissue engineering applications. Full article

Additive manufacturing (AM), also referred to as three-dimensional printing/printed (3DP), has emerged as a transformative approach in the current design and manufacturing of various biomaterials for the restoration of damaged tissues inside the body. This advancement has greatly aided the development of customized biomedical devices including implants, prosthetics, and orthotics that are specific to the patients. In tissue engineering (TE), AM enables the fabrication of complex structures that promote desirable cellular responses in the regeneration of tissues. Since the choice of biomaterials plays a vital role in scaffold performance as well as cellular responses, meticulous material selection is essential in optimizing the functionality of scaffolds. These scaffolds often possess certain characteristics such as biodegradability, biocompatibility, biomimicry, and porous structure. To this end, polymers such as chitosan, collagen, alginate, hyaluronic acid, polyglycolic acid, polylactic acid, and polycaprolactone have been extensively investigated in the fabrication of tissue-engineered scaffolds. Furthermore, combinations of biomaterials are also utilized to further enhance the scaffolds’ performance and functionality. This review discusses the principle of AM and explores recent advancements in AM technologies in the development of TE and regenerative medicine. In addition, the applications of 3DP, polymer-based scaffolds will be highlighted. Full article