Search Results (1,235)

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

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration. Full article

This review systematically outlines recent advances in long-acting microneedle-based transdermal drug delivery systems. It begins by introducing the fundamental principles of microneedles (MNs) as a minimally invasive technology and categorizes them by delivery mechanism into solid, coated, dissolving, hollow, hydrogel-forming, and biodegradable types. The review then discusses the design strategies and material platforms engineered for sustained drug release. A key focus is on biodegradable synthetic polymers, such as polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL), and natural polymers like silk fibroin (SF) and chitosan (CS), which enable prolonged drug release through their tunable degradation rates. Furthermore, it describes the incorporation of advanced drug carriers, including liposomes and polymeric nanoparticles/microparticles, into MNs to further extend release duration and enhance drug-loading capacity. Finally, the major challenges for clinical translation are addressed, including ensuring batch-to-batch consistency in manufacturing, maintaining sterility, and the necessity for more comprehensive validation of long-term in vivo efficacy and safety. Full article

The osteochondral interface (OCI) is a structurally and functionally complex tissue whose degeneration or injury often results in poor healing and joint dysfunction due to its avascular and hypocellular nature. Conventional surgical treatments remain suboptimal, prompting growing interest in regenerative approaches, particularly with the utilization of hydrogel-based biomaterials that can mimic the extracellular matrix and support osteochondral regeneration. This study reviewed types of hydrogels, scaffold processing techniques, and animal models for OCI regeneration. Our search demonstrated that gelatin, alginate, chitosan, and hyaluronic acid were the most frequently investigated hydrogels. Layered constructs dominated current scaffold designs, while advanced methods such as 3D printing and extrusion demonstrated unique potential to create graded architectures resembling the native OCI. Rabbits were the most widely used in vivo models, though translation will require larger animal studies with clinically relevant defect sizes. Future efforts should focus on developing mechanically reinforced, biologically active, and continuously graded hydrogels, supported by standardized preclinical validation in large-animal models, to accelerate translation toward clinical solutions for osteochondral regeneration. Full article

Naturally occurring bioactive compounds represent a promising option for cancer prevention and therapy due to their ability to modulate apoptosis, angiogenesis, inflammation, oxidative stress, and cell signaling. However, their clinical impact is limited by low bioavailability, chemical instability, rapid metabolism, and poor tumor microenvironment accumulation. Innovative delivery platforms, including lipid and polymeric nanoparticles, liposomes, micelles, nanoemulsions, hydrogels, and stimulus-responsive systems, have been developed to improve stability, absorption, tumor specificity, and therapeutic efficacy. This review integrates molecular mechanisms, preclinical and clinical evidence, and recent technological advances, highlighting both potential and limitations. Although several compounds show encouraging results in cell and animal models, only a small number have progressed to early clinical trials, where outcomes remain heterogeneous and often fail to replicate preclinical magnitudes. Regulatory barriers, a lack of formulation standardization, and the absence of predictive biomarkers persist. Sustainability is also addressed through the valorization of agrifood by-products and green extraction processes. This review provides an integrative framework linking molecular mechanisms, advanced delivery technologies, clinical translation, and sustainability, offering a broader perspective than conventional reviews. Future perspectives emphasize multicenter trials, comparative designs, and the development of regulatory guidelines for nanoformulated bioactive compounds. Full article

Peripheral nerve injuries often recover poorly. Hyaluronic acid (HA) biomaterials, with regenerative and anti-fibrotic properties, may augment repair. We performed a PRISMA-guided systematic review of PubMed, Scopus, Web of Science, and Embase (January 2000–August 2024), capturing in vitro, in vivo, and clinical investigations of HA in peripheral nerve repair; data on study context, interventions, and outcomes were extracted. Screening and extraction were performed in duplicate. Forty-eight studies met inclusion criteria. Across in vitro and in vivo models, HA-based biomaterials consistently reduced perineural fibrosis, enhanced axonal regeneration, and improved SFI, CMAP, and NCV compared with conventional repair. Several HA hydrogels and composite conduits achieved functional outcomes approaching autografts, particularly when combined with exosomes, neurotrophic factors, or mechanobiologically tuned scaffolds. Early clinical studies demonstrated safety but remain limited by size and short follow-up. Overall, HA-containing biomaterials appear anti-fibrotic, neuroprotective, and pro-regenerative, supporting their promise as adjuncts for peripheral nerve reconstruction. For this to translate into clinical practice, future work should standardize formulations and dosing, employ rigorous, clinically relevant animal models with long-term endpoints, and advance well-powered, controlled trials to test effectiveness and durability in patients. Clinically, HA platforms show promise as anti-adhesion barriers after neurolysis and as biofunctional fillers/coatings for nerve conduits, but standardized formulations and adequately powered trials are needed to define indications and dosing. Full article

Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug–matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots. Full article

Disorders of skin wound healing and the repair of full-thickness skin defects remain significant clinical challenges. Natural polysaccharide-based hydrogels, with their excellent biocompatibility, tunable degradability, and multifunctional properties (e.g., antibacterial, antioxidant, and pro-angiogenic), have emerged as key materials for designing wound dressings and skin tissue engineering scaffolds. This review systematically summarizes recent advances in polysaccharide hydrogels—including chitosan, hyaluronic acid, and alginate—focusing on material types, crosslinking strategies, and functional modifications, with particular emphasis on their dual applications in wound healing (acute and chronic wounds) and skin tissue engineering. In wound healing, these hydrogels regulate the microenvironment through multiple mechanisms, including anti-inflammatory, antioxidant, pro-angiogenic, and immunomodulatory effects. In skin tissue engineering, their three-dimensional porous structures mimic the extracellular matrix, supporting cell adhesion, proliferation, and tissue regeneration. Finally, we discuss the challenges and future prospects for the clinical translation and commercialization of natural polysaccharide hydrogels. Full article

Despite the advances in medical therapies for treating myocardial infarction (MI), morbidity and mortality rates remain high. Following MI, increased methylglyoxal (MG) production leads to the accumulation of advanced glycation end-products (AGEs), which contribute to adverse remodeling and to the deterioration of cardiac function. We previously reported that an injectable collagen type I hydrogel improves the repair and function of mouse hearts post-MI. Notably, we observed that the injected hydrogel was a target for MG-AGE glycation, and that there were less MG-modified proteins in the myocardium. In this study, we further evaluated this protective mechanism by pre-glycating the hydrogels and assessing their therapeutic efficacy for treating MI. In vitro experiments showed that the viability of macrophages was reduced when cultured with the glycated hydrogel in the presence of MG. In vivo, female C57BL/6 mice were randomly assigned to receive intramyocardial injections of one of three treatments: phosphate-buffered saline, normal collagen hydrogel, or MG-glycated hydrogel. After 28 days, echocardiography was performed to evaluate cardiac function, and hearts were harvested for immunohistochemistry. Our results showed that the MG-glycated hydrogel had a reduced treatment effect (greater scar size, fewer wound-healing macrophages, less viable myocardium and decreased cardiac function) compared to mice that received the normal collagen hydrogel. In summary, this study demonstrates that the ability of the collagen hydrogel to act as a target for glycation and remove MG from the environment contributes to its therapeutic effect in treating the post-MI heart. Full article

Microfluidic cell culture systems and organ-on-a-chip platforms provide powerful tools for modeling physiological processes, disease progression, and drug responses under controlled microenvironmental conditions. These technologies rely on diverse cell culture methodologies, including 2D and 3D culture formats, spheroids, scaffold-based systems, hydrogels, and organoid models, to recapitulate tissue-level functions and generate rich, multiparametric datasets through high-resolution imaging, integrated sensors, and biochemical assays. The heterogeneity and volume of these data introduce substantial challenges in pre-processing, feature extraction, multimodal integration, and biological interpretation. Artificial intelligence (AI), particularly machine learning and deep learning, offers solutions to these analytical bottlenecks by enabling automated phenotyping, predictive modeling, and real-time control of microfluidic environments. Recent advances also highlight the importance of technical frameworks such as dimensionality reduction, explainable feature selection, spectral pre-processing, lightweight on-chip inference models, and privacy-preserving approaches that support robust and deployable AI–microfluidic workflows. AI-enabled microfluidic and organ-on-a-chip systems now span a broad application spectrum, including cancer biology, drug screening, toxicity testing, microbial and environmental monitoring, pathogen detection, angiogenesis studies, nerve-on-a-chip models, and exosome-based diagnostics. These platforms also hold increasing potential for precision medicine, where AI can support individualized therapeutic prediction using patient-derived cells and organoids. As the field moves toward more interpretable and autonomous systems, explainable AI will be essential for ensuring transparency, regulatory acceptance, and biological insight. Recent AI-enabled applications in cancer modeling, drug screening, etc., highlight how deep learning can enable precise detection of phenotypic shifts, classify therapeutic responses with high accuracy, and support closed-loop regulation of microfluidic environments. These studies demonstrate that AI can transform microfluidic systems from static culture platforms into adaptive, data-driven experimental tools capable of enhancing assay reproducibility, accelerating drug discovery, and supporting personalized therapeutic decision-making. This narrative review synthesizes current progress, technical challenges, and future opportunities at the intersection of AI, microfluidic cell culture platforms, and advanced organ-on-a-chip systems, highlighting their emerging role in precision health and next-generation biomedical research. Full article

Vanillin (4-hydroxy-3-methoxybenzaldehyde) is widely recognized for its aromatic flavor and established pharmacological properties, including antioxidant, antimicrobial, anti-inflammatory, and anticancer effects. While these biological activities underpin its therapeutic potential, recent advances have expanded the application of vanillin into the field of biomaterials. In particular, vanillin’s unique chemical structure enables its use as a multifunctional building block for the development of innovative hydrogels with dynamic covalent bonding, injectability, and self-healing capabilities. Vanillin-based hydrogels have demonstrated promising applications in wound healing, drug delivery, tissue engineering, and antimicrobial platforms, combining structural support with intrinsic bioactivity. These hydrogels benefit from vanillin’s biocompatibility and functional versatility, enhancing mechanical properties and therapeutic efficacy. This review provides an overview of vanillin’s pharmacological effects, with a primary focus on the synthesis, properties, and biomedical applications of vanillin-derived hydrogels. By highlighting recent material innovations and their translational potential, we aim to position vanillin as a valuable natural compound bridging bioactivity and biomaterial science for future clinical and therapeutic advancements. Full article

This paper proposes a potential solution to the current issue of developing advanced, biocompatible biomaterials with integrated therapeutic functionality, which would contribute to improving the treatment of skin defects. This study aimed to develop, characterize and evaluate hydrogels based on type I collagen, pectin, alginate and myrtle essential oil, in order to obtain biomaterials with potential in skin regeneration applications. Hydrogels incorporating alginate, pectin, type I collagen and Myrtus communis essential oil were prepared via a multistep procedure comprising homogenization, crosslinking and lyophilization. The obtained hydrogels were characterized by physicochemical and structural methods, such as FTIR spectroscopy, to identify interactions between components; micro-computed tomography, to evaluate internal morphology and porosity; antibacterial tests, for evaluating the ability of the hydrogel to prevent infections at the application site; and in vitro cellular tests, such as the XTT test or cytotoxicity tests, such as LDH, essential for evaluating the biocompatibility of the hydrogel. The highest viability value was recorded for sample J4 (99.53 ± 11.88%), indicating an exceptional compatibility with the cells used, almost identical to that of the untreated control. The samples showed encouraging results, supporting their potential for applications in wound treatment and skin regeneration. Full article

Multi-component polymer hydrogels present complex physiochemical interactions that make accurate compositional analysis challenging. This study evaluates three analytical techniques: Nuclear Magnetic Resonance (NMR), Advanced Polymer Chromatography (APC), and Thermogravimetric Analysis (TGA) to quantify polyvinyl alcohol (PVA) and polyethylene glycol (PEG) content in hybrid freeze-thaw derived PVA/PEG/PVP hydrogels. Hydrogels were synthesized using an adapted freeze–thaw method across a wide range of PVA:PEG ratios, with PVP included at 1 wt% to assess potential intermolecular effects. NMR and APC reliably quantified polymer content with low average errors of 2.77% and 2.01%, respectively, and were unaffected by phase separation or hydrogen bonding within the composite matrix. TGA enabled accurate quantification at PVA contents ≤ 62.5%, where PEG and PVA maintained distinct thermal decomposition behaviors. At higher PVA concentrations, increased hydrogen bonding and crystalline restructuring, confirmed by FTIR through shifts near 1140 cm⁻¹ and significant changes in the -OH region, altered thermal profiles and reduced TGA accuracy. Together, these findings establish APC as a high-throughput alternative to NMR for multi-component polymer analysis and outline critical thermal and structural thresholds that influence TGA-based quantification. This work provides a framework for characterizing complex polymer networks in biomedical hydrogel systems. Full article

Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article

Injectable hydrogels (IHs) have gained considerable interest in biomedical and aesthetic applications due to their minimally invasive delivery, selective localization, and sustained release of bioactive agents. They exhibit flowability during administration and undergo in situ gelation under physiological conditions. These behaviors are influenced by their tunable structural, physical, mechanical, and viscoelastic properties, modulating performance. Rheological parameters, including viscosity (η), storage modulus (G′), loss modulus (G″), and yield stress (τ_y) of IHs with time (t), shear rate ($\stackrel{·}{\gamma }$), and frequency (f), explaining their shear thinning, thixotropy, viscoelasticity, and gelatin kinetics, serve as key quantitative indicators of their injectability, self-healing capability, and structural and mechanical stability. The rheological characteristics reflect molecular interactions and crosslinking mechanisms within IH networks, thereby linking formulation to provide overall performance, including injectability, biodegradability, and controlled release. This review summarizes recent advances in IHs for diverse applications, with a primary focus on their rheological properties. It also briefly addresses their composition, intermolecular interactions, and correlated function and performance. The applications discussed include hemostatic and wound dressings, tissue engineering and regenerative medicine scaffolds, drug delivery systems, reconstructive and aesthetic materials, and functional bioinks for 3D printing. Overall, this review demonstrates that rheological characterization provides an essential framework for the rational engineering of next-generation IH systems. Full article