Search Results (1,261)

Articular cartilage defects affect millions of patients annually and pose one of the most persistent challenges in orthopedic surgery, owing to the tissue’s inherent avascular and alymphatic nature. Current surgical approaches, microfracture, autologous chondrocyte implantation (ACI/MACI), and osteochondral grafting, share a common failure mode: inadequate adhesion between repair constructs and surrounding native cartilage, contributing to deterioration rates of 15–75% at five-year follow-up across all techniques. This review repositions adhesion not as a supplementary material property but as the central determinant of clinical success in cartilage repair. We systematically evaluate the biomechanical demands imposed by the joint environment and define clinically relevant adhesion thresholds. Adhesive hydrogel strategies are categorized by surgical context: microfracture augmentation, ACI/MACI enhancement, osteochondral graft integration, and standalone repair platforms. Material platforms are analyzed across catechol/dopamine systems, NHS ester chemistry, photocrosslinkable hydrogels, supramolecular approaches, and multi-mechanism hybrids. Injectable formulations for arthroscopic delivery are critically examined alongside key translational barriers, including fatigue durability, biocompatibility–adhesion trade-offs, sterilization compatibility, batch variability, and regulatory classification ambiguity. Future directions encompass 4D bioprinting, AI-guided formulation optimization, and stimuli-responsive reversible adhesion systems. Adhesive hydrogels represent the missing link that current cartilage repair paradigms require. Full article

3D bioprinting technology has made great strides in the field of bone tissue engineering. It has been able to create personalized biological structures on a macroscopic scale. In terms of microstructure bionics, 3D printing technology has also made some progress in recent years. The use of nanotechnology and drug delivery technology has provided a microenvironment that is more compatible with cell growth. Finally, it is possible to bridge the gap between engineered organizational structures and natural tissues. In this work, we summarize the widely used 3D bioprinting methods and the preparation of bioinks. Next, the classification of bone tissue engineering scaffold materials and nanomaterials for loading is briefly introduced. Then the technical shortcomings of current nanotechnology-based 3D bioprinting are described, along with the corresponding improvements. Finally, we summarize the prospects of nano-based 3D bioprinting technology in bone tissue engineering. Full article

Poor vascularization is one of the basic obstacles to the regeneration of functioning tissues because an oxygen diffusion process and elimination of wastes are essential in preserving the grafts. Recently, biomaterials have allowed the invention of bioinspired polymer scaffolds and replicated the natural extracellular matrix (ECM) due to the mechanical tunability of the synthetic polymers with the biological signals of natural macromolecules. The review uses a mechanistic analysis of the strategies to improve angiogenesis by using surface topography modification, bioactive peptide incorporation and pre-vascularization. Another way to achieve complex, perfusable topologies is by using more sophisticated methods of fabrication, such as electrospinning, 3D/4D bioprinting, or microfluidics. Based on in vitro and in vivo results, we determine angiogenic effectiveness by using cellular assays and animal transfers, pointing towards the translational advances in patents and clinical uses of bone, cardiac, nervous, and skin tissues. In spite of the substantial improvements, large-scale production and high demands of the regulations still exist. The future directions include the incorporation of bioinspired designs and intelligent materials, nanotechnology, and AI-based optimization into developing patient-specific and adaptive scaffolds. The following innovations herald the advent of highly effective constructs that can be used to regenerate tissue and overcome the limitations of present tissue engineering therapies through the introduction of highly effective, vascularized constructs. Full article

The development of biomimetic and mechanically functional constructs remains a major challenge in skeletal muscle tissue engineering. In this study, we present a multi-component 3D bioprinted platform integrating a polycaprolactone (PCL) support for mechanical stimulation, a sacrificial gelatin (GE) matrix for controlled bioink deposition, and collagen-based bioinks laden with Rattus norvegicus L6 skeletal muscle cells. The influence of PCL architecture, GE concentration (0.75, 1.5 and 3 wt%), and bioink composition—collagen (C), collagen–Matrigel (CM), and extracellular matrix-based (ECM)—was systematically evaluated. Rheological characterization demonstrated that all bioinks exhibited shear-thinning behavior and suitable viscoelastic properties for extrusion-based bioprinting, with sufficient mechanical stability to withstand dynamic bioreactor conditions. Microstructural analysis revealed highly interconnected porous networks, particularly in ECM-based scaffolds. While no statistically significant differences were observed, the ECM-based bioinks showed the highest cell viability and improved structural organization. Overall, this work demonstrates a versatile bioprinting strategy that combines mechanical support and biomimetic environments, highlighting the potential of ECM-based bioinks for the fabrication of functional skeletal muscle constructs. Full article

Tissue engineering represents a central strategy in regenerative medicine to restore damaged or missing tissue through structural and functional replacement. In this study, a two-component bioink platform was developed based on amine–anhydride conjugation as a mild crosslinking reaction between synthetic anhydride-containing oligomers (oSMoMA-x) and natural biopolymers. The compatibility of the oligomers with different amine-containing biopolymers, including chitosan, gelatin, and hydrolyzed collagen peptides, was systematically evaluated. To improve cytocompatibility and enable controlled network formation, oSMoMA oligomers with varying anhydride contents were synthesized and characterized, allowing targeted tuning of material properties through comonomer composition. The resulting hydrogels were comparatively assessed with respect to their rheological and physicochemical properties. While hydrogel formation was achieved with all investigated biopolymers, gelatin-based systems exhibited the most favorable characteristics for bioink development. Two gelatin/oSMoMA bioink formulations with distinct gelation behavior were obtained by employing different base catalysts, enabling control over crosslinking kinetics and material properties. Cytocompatibility was comprehensively evaluated using viability assays, demonstrating enhanced metabolic activity of cells encapsulated in gelatin/oSMoMA-3.5 hydrogels compared to established reference systems, with sustained compatibility for up to seven days. Extrusion-based 3D bioprinting was performed using a modified printhead with integrated temperature control to maintain physiological conditions. The bioinks were successfully printed with embedded murine 3T3 fibroblasts, and post-printing analyses confirmed cell proliferation within the hydrogel constructs. Overall, the results demonstrate the broad compatibility of amin–anhydride-crosslinked oSMoMA systems with different biopolymers and highlight gelatin/oSMoMA bioinks as promising cytocompatible materials for stable 3D bioprinting applications in tissue engineering. Full article

The advancement of modern regenerative medicine is closely associated with additive technologies that enable the creation of tissue-engineered constructs and personalized bioprostheses. Three-dimensional bioprinting allows precise modeling of tissue architecture and extracellular matrix microstructures. Recent studies demonstrate rapid growth in the use of 3D bioprinting for biomedical applications including regenerative medicine, pharmaceutical research, and biotechnology. Special attention is given to the development of bioinks that combine biological and structural functions and maintain cell viability during printing. Modern technologies allow the fabrication of skin, bone, vascular, and cartilage tissues with high structural accuracy. The technology is also actively used in reconstructive surgery for the production of personalized implants. However, challenges remain related to vascularization, standardization of materials, and ethical aspects of clinical use. This review summarizes the main principles of 3D bioprinting, technological approaches, biomedical applications, and future perspectives of additive technologies in regenerative medicine. Full article

Hyaluronic acid (HA), a native non-sulfated glycosaminoglycan of the extracellular matrix, has emerged as a central biomaterial in tissue engineering due to its biocompatibility, hydration capacity, and receptor-mediated bioactivity. Beyond its structural role, HA actively regulates cellular behaviors through interactions with receptors such as CD44 and RHAMM, with outcomes highly dependent on molecular weight, degradation state, and matrix context. Recent advances in chemical modification and crosslinking strategies have enabled the development of HA-based hydrogels, nanofibers, and composite systems with tunable mechanics and degradation profiles, supporting applications in bone, cartilage, vascular, and skin regeneration, as well as in emerging platforms such as 3D bioprinting and nanomedicine. However, inconsistent biological responses and limited clinical translation remain key challenges. This review integrates current understanding of HA synthesis, physicochemical properties, degradation, and receptor-mediated signaling, and establishes a mechanistic framework linking molecular characteristics, matrix mechanics, and cell responses. Building on this framework, we outline design strategies for multifunctional HA composites, advanced biofabrication approaches, and receptor-targeted systems, providing a basis for the rational engineering of next-generation HA-based biomaterials with improved translational potential. Full article

Hydrogel scaffolds have emerged as a central platform in tissue engineering due to their ability to mimic the extracellular matrix and support cellular functions. Among natural polymers, chitin and its derivative chitosan have emerged as valuable candidates for hydrogel scaffold development because of their biodegradability, compatibility with living tissues, and inherent biological functionality; however, their distinct and complementary roles in hydrogel scaffold design are often insufficiently differentiated in the literature. This review provides a comprehensive and mechanism-driven analysis of chitin- and chitosan-based hydrogel scaffolds, emphasising how their molecular structure governs network formation, mechanical performance, and biological functionality. Chitin is highlighted primarily as a structurally robust and crystalline component suitable for reinforcement. In contrast, chitosan serves as a versatile, soluble, and chemically reactive matrix enabling various crosslinking and functionalization strategies. Recent advances in physical, ionic, and covalent crosslinking as well as composite scaffold engineering, biofunctionalization, and emerging fabrication approaches such as injectable systems and three-dimensional bioprinting are systematically examined. The relationships between scaffold architecture, degradation behaviour, and cellular responses are discussed in key tissue engineering applications, including bone, cartilage, skin, and nerve regeneration. Importantly, this review introduces a unified structure–property–function framework that distinguishes the roles of chitin and chitosan within hydrogel systems and links crosslinking mechanisms to application-specific performance requirements, an aspect not comprehensively addressed in previous studies. Current challenges related to mechanical limitations, material variability, and clinical translation are critically evaluated, and future perspectives for the rational design of next-generation biomimetic hydrogel scaffolds are proposed. Full article

Chronic wounds remain a major clinical and economic burden due to persistent inflammation, impaired perfusion, microbial biofilms, and dysregulated immune responses that collectively stall epithelialization. Polymicrobial bacterial–fungal biofilms, including Candida species, further delay healing by sustaining inflammation and promoting treatment-resistant infection. Recent advances have accelerated the development of bioengineered skin substitutes, collagen matrices, and placental-derived grafts that modulate macrophage polarization, reactive oxygen species signaling, and extracellular matrix remodeling to restore tissue architecture and promote neovascularization. Their effectiveness, however, depends on integration within structured care pathways that emphasize debridement, moisture balance, and infection control. Artificial intelligence, three-dimensional bioprinting, flexible microelectronic sensors for real-time wound monitoring, and bioactive compounds derived from traditional Chinese medicine, are expanding the therapeutic landscape. Together, these innovations support a shift toward predictive, personalized, and regenerative wound-care strategies. This review aims to provide a mechanistic and clinically contextualized overview of advanced grafting biomaterials, highlighting current applications, limitations, and future directions in chronic wound care. Full article

Gel-based flexible electronic sensors have emerged as a transformative class of materials for next-generation applications. These applications are wearable electronics, soft robotics, electronic skin (e-skin), and healthcare monitoring systems. Owing to their intrinsic softness, stretchability, and biocompatibility, gels provide an ideal platform for constructing highly deformable and skin-conformable sensing devices. This paper provides insight into emerging fabrication techniques, including 3D printing, bioprinting, and microfabrication. These techniques have facilitated the creation of complex architectures with improved sensitivity and scalability. The review also focuses on recent advancements that have focused on overcoming traditional limitations. These limitations are poor mechanical strength, dehydration, limited environmental stability, and low sensitivity. In particular, the incorporation of conductive fillers and ionic species has enabled a range of sensing mechanisms. These mechanisms include piezoresistive, capacitive, piezoelectric, and ionotronic responses. Therefore, it allows for the accurate detection of strain, pressure, temperature, and biochemical signals. Finally, this review provides a summary of future research, which is expected to focus on multifunctional integration, sustainable materials, and intelligent data processing. It provides pathways to the widespread adoption of gel-based flexible electronic sensors in both consumer and clinical applications. Full article

For personalized treatments, including soft tissues repair, the use of in situ bioprinting is of increased interest. Many soft tissues, such as sphincters, have poorly known mechanical properties and a complex structure, with limited options for a medical practitioner to assess where the injections should be made and how much should be injected. The rate of injection and its variation have a direct implication on pain sensation for patients, but post-injection efficacy largely depends on the ability of the hydrogel to adapt to local loads and displacements, keeping the 3D structure compliant to the surrounding tissues. Such a method is known as ‘in situ bioprinting’. There are, however, limited data regarding hydrogels’ functionalities for such applications, and many commercial hydrogels, as medical devices, are used off-label. This study aims to introduce an innovative, robust, and reliable approach for evaluating the ejection-related mechanical properties of various commercial hydrogels. The ejectability of six clinically approved hydrogels was assessed through their rheological properties, characterized by measuring apparent viscosity using a mechanical testing device in a novel setup combined with the dynamic syringe pump analysis (for a pre-set constant ejection rate). It was shown that a well-established power-law approximation offers a straightforward, less computationally intensive approach than more complex models that attempt to account for viscosity, shear rate, and wall slip. It assesses hydrogel performance within an actual system, including the syringe and nozzle, rather than just characterizing the material in isolation, thus making it particularly valuable for predicting how gels will behave under real conditions. This method can be adapted for specific clinical bioprinting applications, including sphincter repair, lipoatrophy correction, or deep dermal/transdermal targets, optimizing speed, flow rate, and applied force. Full article

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and healthcare system priorities, the goal is to develop smart, feasible, long-lasting, cost-effective, readily available, adverse-reaction-free, adaptable, and personalized solutions that minimize patient discomfort, reduce caregiver effort, and decrease hospitalization duration and costs. In this context, biomaterials serve as versatile tools capable of performing a wide range of diagnostic, therapeutic, and theragnostic functions. Thanks to their biocompatibility, biodegradability, surface chemistry, and responsiveness, biomaterials are currently addressing issues such as patient compliance (through controlled drug-delivery systems and smart wound dressings), long transplant waiting lists, transplant rejection, non-adaptable prosthetics (artificial organs), oncology treatment efficacy (nano-formulations for theragnostics and multiple tumor targeting), and inconsistent in vitro drug-testing models (organs-on-a-chip). In this review, we focus on biomaterials’ smartness, then explore databases for efficient product design, and finally highlight their applications in the biomedical field, especially in drug delivery, tissue engineering, and regenerative medicine. Full article

Gelatin–alginate composite hydrogels are some of the most prevalent bioinks used for extrusion-based three-dimensional (3D) bioprinting because of their combined bioactivity and ability to ionically crosslink. Ionically crosslinked gelatin–alginate constructs containing human bone marrow–derived mesenchymal stem cells (hBM-MSCs) were characterised over time under standardised in vitro conditions to assess physicochemical properties and resultant cell behaviour. Water uptake and degradation were quantified over time in phosphate-buffered saline (PBS) and collagenase type II media for up to 21 days. Cell viability and metabolic activity were quantified, and osteogenic gene expression (RUNX2, COL1A1, OCN) was assessed. Raman spectroscopy and compressive mechanical characterisation were performed. Collagen and glycosaminoglycan-related peaks were observed from extracellular matrix (ECM)-associated components, with an increased presence of protein-associated signatures later in culture. Hydrogels displayed nonlinear elastic behaviour with increased stress after longer incubation times, suggesting no degradation of mechanical integrity over the duration of the study. Hydrogels experienced rapid hydration followed by decreased swelling over time, with a maximum swelling ratio at 24 h. Degradation rates significantly increased over longer incubation times (p < 0.001) and in collagenase media compared to PBS (p < 0.001). Observed differences were likely due to both ion-exchange-mediated network disassembly and the dissolution of gelatin components. Cell metabolic activity decreased under osteogenic culture conditions, while changes in osteogenic marker expression were sequential, suggesting a transition from proliferation to early osteogenic commitment in this 3D system. This work provides both physicochemical and biological characterisation of a commonly utilised gelatin–alginate bioink system, to provide future optimisations within the field of extrusion-based bone tissue engineering, a reproducible baseline for future optimisation of bioink systems in extrusion-based bone tissue engineering. Full article

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article

The fabrication of complex architectures remains a central challenge in 3D bioprinting, as the low mechanical properties of hydrogels limit the range of achievable geometries. Four-dimensional (4D) bioprinting can address these limitations by enabling programmed shape-morphing behavior; however, in most approaches, this functionality is introduced after hydrogel formation, limiting the complexity of the resulting deformation. Here, a proof-of-concept strategy is presented, in which shape-morphing is directly encoded during fabrication. By modulating light exposure time layer-by-layer in vat photopolymerization, spatial variations in crosslinking density are introduced in situ within Gelatin Methacryloyl (GelMA) hydrogel constructs. Exposure times in the range of 20–70 s were investigated, enabling controlled bending of the printed structures upon immersion in aqueous media, with radii of curvature between 11 and 20 mm depending on the geometry. This approach allows deformation pathways to be programmed during printing, without requiring additional materials or post-processing steps. The morphing behavior was further supported by finite element simulations, which reproduced the experimentally observed deformation and enabled prediction of the shape change. In addition, high cell viability (>95%) was maintained after material contact and UV exposure. Overall, this study demonstrates that swelling-driven actuation can be encoded during fabrication. Although demonstrated on simplified geometries, this approach provides a versatile framework for process-driven shape-morphing and represents a step toward more spatially resolved and potentially volumetric 4D bioprinting strategies. Full article