Search Results (1,756)

Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm² of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm²), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration. Full article

Background: The generation of durable and hemocompatible small-diameter vascular grafts remains a major challenge in current vascular tissue engineering, as clinically available synthetic grafts are lacking hemocompatibility resulting in limited long-term patency. In recent years, fibrin has emerged as a promising scaffold material for various tissue engineering approaches due to its autologous nature, controllable fabrication, and mechanical properties. However, although pivotal for the translation into clinical application, systematic evaluation of hemocompatibility in fibrin-based small-caliber grafts is still missing. Methods: Here, the hemocompatibility of small-diameter fibrin-based grafts with and without heparin coating was compared to the current gold standard for prosthetic small-diameter vessel replacement in the form of heparin-coated ePTFE grafts using the Chandler Loop circulation model with human whole blood. Cell adhesion of thrombocytes, erythrocytes, and leucocytes was compared. Platelet activation, activation of the complement system, and plasmatic coagulation activity were assessed by ELISA analyses for P-Selectin, complement sC5b-9, and thrombin–antithrombin complex, respectively. Scanning electron microscopy (SEM) was performed to evaluate interactions and thrombocyte activation on the luminal graft surfaces. Results: The short-term hemocompatibility of the fibrin-based grafts with respect to the cell-count, activation of the coagulation pathways, and thrombocyte activation was comparable to the heparin-coated synthetic grafts even without heparin coating of the bioartificial grafts. Conclusions: The findings of this early-stage analysis support fibrin as a promising scaffold material for small-diameter vascular tissue engineering. Full article

This study presents a transformative “one-pot” biorefinery approach for the simultaneous production of hyaluronic acid (HA) and polyhydroxybutyrate (PHB) using an engineered, non-pathogenic Halomonas bluephagenesis TD01 chassis. By leveraging the principles of Next-Generation Industrial Biotechnology (NGIB), a one-step fermentation process was developed in nutrient-rich 40-LBG-Y medium, achieving a balanced metabolic flux that yielded 1.99 g/L and high-molecular-weight (HMw) HA (9.6 × 10⁶ Da) as the highest HA-Mw reported by heterogeneous bacteria, alongside intracellular PHB (0.68 to 1.6 g/L). A bioactive HA-PHB nanoparticle scaffold was fabricated, exhibiting a highly porous, interconnected 3D sponge-like architecture with a significant particle size shift from 12 nm to 450 nm, confirming successful polymer complexation. Antimicrobial evaluations revealed that the scaffold exhibited preliminary antimicrobial potential against representative Gram-positive and Gram-negative strains against Staphylococcus aureus, Klebsiella variicola, and Candida albicans. Notably, while Pseudomonas aeruginosa metabolically exploited purified HA, the integrated scaffold reversed this effect, providing preliminary antimicrobial potential by sterically hindering bacterial hyaluronidases. Furthermore, Halomonas-derived HA consistently outperformed Moringa oil and complex emulsions in preliminary tests against a wide range of pathogenic microbes. These results demonstrate that this dual-product platform provides a sustainable, cost-effective source of high-performance functional materials for advanced antimicrobial coatings and clinical wound management. Full article

The extracellular matrix (ECM) provides a dynamic microenvironment that regulates cell proliferation, migration, and tissue remodeling during wound healing. However, replicating the structural and functional complexity and ECM heterogeneity of native skin ECM remains challenging with conventional single-material hydrogels. Recent advances in multimaterial 3D bioprinting have enabled the spatial integration of diverse biomaterials within a single construct. Lignocellulose has attracted increasing attention as a promising biomaterial for recreating key structural features of the native ECM because of its fibrous architecture, mechanical strength, and biocompatibility. This review offers a comprehensive and integrated perspective on the use of lignocellulose-based multimaterial printing to recreate ECM-mimicking architectures, an underexplored area at the intersection of biomaterials and biofabrication. The roles of cellulose, hemicellulose, and lignin in printability, scaffold stability, porosity, bioactivity, and wound-healing performance are discussed. Representative studies have demonstrated that lignocellulose-based multimaterial bioinks provide porous architectures that support cell adhesion, proliferation, and tissue regeneration. These benefits are accompanied by improved mechanical performance, as cellulose nanofibers exhibit elastic moduli exceeding 100 GPa, and lignin-containing hydrogels have achieved compressive moduli of up to 135 kPa. Such mechanical advantages make lignocellulosic materials particularly attractive for fabricating ECM-mimicking scaffolds that require long-term structural integrity. Finally, key design considerations and current limitations associated with lignocellulose-based multimaterial bioprinting are critically discussed. A framework for the rational design of lignocellulose-based multimaterial bioinks is presented, together with future directions toward gradient and adaptive scaffolds, smart wound dressings, and advanced wound-healing applications. Full article

Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters increasingly explored as sustainable biomaterials for regenerative medicine. This review summarizes recent advances in PHA-based bone substitute materials, highlighting their properties, fabrication methods, and biological performance. PHAs combine biocompatibility, tunable mechanical behavior, and degradation into non-toxic metabolites, while copolymerization and monomer selection modulate the stiffness, crystallinity, and resorption rate. Processing techniques such as solvent casting, electrospinning, and additive manufacturing allow the production of porous architectures that mimic bone extracellular matrix. Electrospinning is particularly suitable for nanoscale fibrous matrices, whereas 3D printing enables patient-specific scaffolds with controlled geometry and interconnected porosity. Scaffold performance can be further improved through the incorporation of osteoconductive fillers, including hydroxyapatite, β-tricalcium phosphate, bioactive glasses, graphene oxide, and carbon nanotubes, as well as through drug-delivery and pro-angiogenic functionalization. In vitro and in vivo studies consistently report favorable cytocompatibility, enhanced osteogenic differentiation, vascularization, and effective repair of bone defects in animal models. However, clinical translation remains limited by production costs, variability in polymer quality, thermal processing constraints, and regulatory challenges. Future progress will rely on more efficient biosynthesis, medical-grade purification, multifunctional scaffold design, and stronger collaboration between academia, industry, and clinicians to unlock the full potential of PHAs in regenerative bone therapies. Full article

Periodontal disease remains one of the leading causes of tooth loss worldwide, highlighting the need for effective regeneration of alveolar bone, periodontal ligament, and cementum. The structural complexity and unique biological behavior of these tissues have historically posed significant challenges for clinical regeneration strategies. The primary therapeutic approach used is guided bone regeneration; however, it has certain limitations, such as morbidity, low structural integrity and dimensional stability. Recent advances in 3-dimensional (3D) bioprinting have made it possible to fabricate customized scaffolds with precise architecture and spatial organization that closely mimic normal periodontal structures. The incorporation of multifunctional nanocomposite biomaterials and nanoparticles further enhances the performance of the scaffolds by increasing mechanical strength, bioactivity and controlling degradation rates. These advanced scaffolds function as dynamic microenvironments that support cell adhesion, proliferation and differentiation, ultimately promoting tissue regeneration. Furthermore, their multifunctional properties allow for the controlled release of growth factors, anti-inflammatory and antimicrobial agents, as well as the incorporation of stem cells and bioactive molecules that facilitate angiogenesis. This review investigates and critically evaluates modern approaches for the regeneration of periodontal tissues through scaffolds, biomaterials and 3D bioprinting technologies, as well as to assess their effectiveness compared to established clinical practices. Full article

Cutaneous tissue engineering has advanced from simple coverage substitutes to increasingly complex living constructs, yet the field remains constrained by a decisive problem: timely and durable perfusion. Many engineered skin substitutes can appear vascular in static culture or in small-animal models. However, they still fail when blood flow must be established quickly enough to rescue cells across clinically relevant tissue thickness. Rather than re-catalog platforms already summarized in recent reviews, this critical narrative review reframes the field around perfusion as the master functional endpoint rather than vessel density alone. We analyze the vascularization bottleneck as a sequence, internal network formation, host inosculation, flow initiation, and perfusion stability—and use that sequence to reassess biomaterial design, cell-based strategies, immunomodulation, decellularized matrices, bioprinting, microfluidics, and prevascularization. We intentionally distinguish implantable skin substitutes from perfused in vitro platforms such as skin-on-chip systems, arguing that these are linked but non-interchangeable application spaces with different success criteria. Building on this distinction, we propose a research agenda centered on functional benchmarking of perfusion, spatiotemporal coordination of scaffold dynamics, immune–mural–lymphatic–vascular crosstalk, scalable hierarchical vascular fabrication, and predictive human test platforms. The central argument is that translation will depend not on ever more isolated pro-angiogenic interventions but on integrated systems that survive the ischemic interval, connect rapidly, tolerate blood entry, maintain a workable inflow–outflow balance, and remodel into a stable, skin-specific microvasculature. Full article

Background: Conventional and refractory wounds frequently remain in a prolonged inflammatory phase associated with excessive reactive oxygen species (ROS) accumulation and disruption of endogenous electrical cues. Methods: A multifunctional nanocomposite hydrogel was fabricated via an amidation condensation reaction, utilizing 3-amino-4-methoxybenzoic acid (AMB)-modified carboxymethyl chitosan (PAMB-CMCS) and decellularized extracellular matrix (dECM) as macromolecular networks, integrated with Astragaloside IV-Loaded Polydopamine/Zeolitic Imidazolate Framework-8 (AS@PDA/ZIF-8) nanoparticles. Results: The hydrogel provided a biomechanically supportive scaffold with compressive strength of 27.24 ± 1.9 kPa and breaking strength of 28.2 ± 2.8 kPa and exhibited electrical conductivity of 29.84 mS/cm, ROS-scavenging activity, and near-infrared (NIR)-responsive photothermal behavior reaching 62.55 °C. The integrated PDA@ZIF-8 nanoplatform further contributed to antibacterial performance and localized AS release, thereby improving the wound microenvironment and accelerating full-thickness cutaneous defect repair. Conclusions: This macromolecule-based composite hydrogel offers a promising therapeutic strategy for complex wound management. Full article

Three-dimensional scaffolds based on triply periodic minimal surfaces (TPMSs) have attracted growing interest in bone tissue engineering because of their high interconnectivity and ability to combine high porosity with mechanical integrity. However, in fused deposition modeling (FDM), printed architecture may systematically deviate from the nominal design, thereby affecting structural fidelity and mechanical performance. This study investigated the influence of FDM processing parameters and nozzle diameter on the effective microarchitecture and compressive elastic modulus of polycaprolactone (PCL) gyroid scaffolds. First, a Taguchi L18 design was used to evaluate the effects of extrusion temperature, printing speed, and flow rate on pore size for two nozzle diameters (0.4 and 0.3 mm). In a second experimental stage, prismatic specimens fabricated at three nominal porosity levels were compression-tested to determine the elastic modulus (E), and measured porosity (ϕ) was quantified by densimetric measurements. A systematic mismatch was observed between the nominal design and the printed scaffold architecture, with both pore size and measured porosity consistently lower than their intended values. The dominant process parameter associated with pore-size variability was nozzle-specific: extrusion temperature contributed most for the 0.4 mm nozzle, whereas printing speed contributed most for the 0.3 mm nozzle. In compression, E decreased with increasing measured porosity, and statistical analysis showed that the E–ϕ relationship was nozzle-dependent. Overall, these findings support a process–structure–property interpretation based on the effective printed microarchitecture rather than on nominal design parameters alone. The experimental stiffness ranges obtained here also provide an exploratory mechanical contextualization relative to reported trabecular bone domains, without implying site-specific scaffold selection. Full article

The synthesis of reactive sucrose derivatives is of significant interest for the development of novel biocompatible polymers. In this study, an octa-substituted sucrose derivative containing isocyanate groups was synthesized via a urethane-forming reaction carried out in an aprotic solvent at the phase interface. This approach exhibits high selectivity and provides a target product yield of up to 60%. Subsequently, using the same reaction mechanism, the isocyanate derivative was converted into an octa-functional methacrylate derivative capable of forming three-dimensional cross-linked networks. The structures of both the intermediate and final products were confirmed by IR, ¹H NMR, and mass spectrometry. The sucrose-based prepolymer was further evaluated in the formation of cross-linked structures for potential application as bone-substituting implants. Using various photocuring techniques, including two-photon 3D printing, both plates and microstructured scaffolds were fabricated. These structures exhibited high thermal stability, elastic properties comparable to those of bone tissue, and no toxic effects on cells. Full article

A composite hydrogel scaffold comprising chitosan, silk fibroin, Aloe vera extract, and Mimosa complex was fabricated and thoroughly characterized. Upon freeze-drying, the scaffolds displayed a uniform cylindrical geometry with a highly porous, interconnected polymeric network. Quantitative image analysis revealed a mean pore diameter of 43.09 ± 2.27 µm alongside an overall porosity of 61.4 ± 6.2%. ATR-FTIR and XRD analyses confirmed successful inclusion of the complex formation and the incorporation of all constituents into the final formulation. The scaffold exhibited a compressive modulus of 46.63 ± 22.71 kPa (dry) and 5.40 ± 3.73 kPa (hydrated), with a swelling ratio of 756.62 ± 114.08%, supporting its suitability for physiological applications. TGF-β3 loading via adsorption yielded an entrapment efficiency of approximately 79.18%, reflecting effective physical immobilization throughout the polymer matrix. Cytocompatibility was subsequently assessed using an indirect contact model combined with an MTT assay, both of which confirmed that TGF-β3-loaded scaffolds exerted no cytotoxic effects on chondrocytes. After 28 days in culture, scanning electron microscopy revealed pronounced cell adhesion, preservation of rounded cell morphology, and ECM deposition along pore walls and throughout interconnected channels. Immunofluorescence analysis further demonstrated a time-dependent accumulation of aggrecan and collagen type II within the three-dimensional scaffold architecture. Collectively, these findings suggest that the developed composite hydrogel scaffold is well-suited for cartilage-related in vitro culture applications. Full article

Effective wound management remains a critical challenge in modern medicine, requiring a delicate balance among infection control, hemostasis, and tissue regeneration. Biopolymer-based hydrogels have emerged as leading candidates for medical use due to their biocompatibility, moisture-retention capabilities, and structural similarity to the natural ECM. This review provides a comprehensive overview of the transition from passive dressings to intelligent, multifunctional hydrogel scaffolds. We first examine the biological mechanisms of wound healing and the fundamental roles of hydrogels in maintaining an optimal microenvironment. Central to this discussion is the integration of conductive materials (including conductive polymers, carbon-based nanomaterials, and metal nanoparticles), which empower hydrogels with bio-sensing and electromechanical stimulation capabilities. Furthermore, we explore how 3D printing technologies enable the fabrication of personalized, high-precision scaffolds. The review also discusses the emerging role of integrated monitoring systems and machine learning algorithms in enhancing diagnostic accuracy. By synthesizing current research, this review identifies critical engineering hurdles and outlines the future trajectory toward automated, closed-loop wound-care systems in clinical practice. Ultimately, while these advanced electronic scaffolds offer revolutionary therapeutic paradigms, this review underscores that balancing electroconductivity with chronic cytocompatibility, refining multi-modal biosensor calibration, and navigating complex regulatory evaluation pathways remain critical prerequisites. Overcoming these fundamental translational bottlenecks is essential to realizing the next generation of automated clinical wound care. Full article

Tissue engineering is widely used in research for investigating cellular proliferation, behavior, and responses to various stimuli. However, the predictive value of preclinical studies using cell culture plates is limited by the inability to recapitulate the complexity of the physiological microenvironment. Synthetic three-dimensional (3D) scaffolds can be engineered to mimic the complex morphology of the extracellular matrix of native tissues and can serve as physiologically relevant platforms for preclinical studies. In this study, 3D electrospun scaffolds were characterized to aid in breast cancer research. Unlike previous studies that focused primarily on scaffold fabrication or cell viability, this work systematically evaluates how scaffold morphology influences breast epithelial and breast cancer cell behavior within three-dimensional microenvironments. Breast cancer cell lines and normal breast epithelial cells were seeded on scaffolds of different morphologies, on commercially available mesh scaffolds, and on standard tissue culture plates. Cells were treated with a fluorescent fructose mimic (ManCou-H) that targets the fructose-specific transporter GLUT5 to assess metabolic activity on different scaffolds. The study evaluated cell–cell and cell–matrix interactions through time-lapse experiments, cell metabolism, and variations in the expression of cytoskeletal protein (CK18) and GLUT5. Statistically relevant differences were observed between cells cultured on scaffolds and plates, and different scaffolds morphologies. Results from this study demonstrate that scaffold topology alone can significantly alter cellular phenotype and metabolic responses, highlighting the importance of scaffold selection in the development of predictive non-animal in vitro models and studies of the tumor microenvironment. Full article

Flexible pressure sensors with a porous architecture are highly desirable for wearable health monitoring and intelligent human–machine interaction, owing to their excellent comfort and conformability to human motion. However, conventional porous sensors often suffer from poor signal accuracy and unstable output, which limit their capability for precision sensing. To address these challenges, we designed and fabricated a flexible pressure sensor with exceptional linearity by mimicking the unique surface structure of Iron Cross Begonia (Begonia masoniana) leaves. The sensor is constructed using a readily available melamine foam as the backbone: a porous sensing scaffold is first obtained via a simple dip-coating process, and a film featuring bioinspired protrusions is fabricated by repeated replica molding. Lamination of these two components yields a stacked sensor device. Characterization demonstrates that the sensor achieves a broad pressure detection range of up to 350 kPa, with a minimum resolvable pressure of 250 Pa, and exhibits an excellent linearity of 0.999 over its entire working range (0–350 kPa). Moreover, the sensor shows stable responses under varying loading frequencies, is capable of detecting low-frequency signals, and retains its performance without notable degradation even after 5000 repeated loading-unloading cycles. In practical applications, the sensor accurately monitors flexion and extension movements of the wrist, finger, neck, and knee, capturing human motion signals with high fidelity. Furthermore, it enables information encoding and transmission through finger gestures. The proposed bioinspired structural design strategy effectively enhances the overall performance of porous pressure sensors, offering a new paradigm for the development of flexible sensing devices with promising applications in wearable health monitoring, human motion detection, and human–machine interaction. Full article

Traumatic tracheal injuries and congenital defects can be life-threatening and are associated with substantial morbidity and mortality. Regenerating the trachea through tissue-engineered scaffolds has emerged as an innovative alternative to traditional therapies that involve tracheal resection with primary end-to-end anastomosis or tracheostomies. Despite significant advances in biomaterial developments, stem cell biology, and novel scaffold fabrication, successful clinical translation of tracheal constructs remains limited. Major challenges include inadequate vascularization following implantation, epithelial regeneration, immune reactions, mechanical instability, infection, and inability of adaptive scaffold systems to withstand long-term tissue remodeling. While general tracheal tissue-engineering techniques and the materials, cell lines, and fabrication methodologies have been previously explored, this review summarizes current advancements in tracheal tissue engineering while emphasizing the mechanobiological and translational barriers that preclude functional tracheal regeneration and clinical success. Emerging knowledge in immunomodulatory biomaterials, dynamic scaffolds, strategic vascularization methods, and adaptable constructs has paved the way for researchers to develop a tracheal scaffold that can be translated into clinical use. This review provides a critical framework that discusses the advantages and potential pitfalls of the aforementioned technologies. Full article