Search Results (39)

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their development and clinical translation. One of the foci is placed on the stringent physicochemical requirements for bioinks, where we examined the critical balance between bioadhesion—facilitated by functional groups—and mechanical cohesion necessary for maintaining structural integrity during deposition, while RGD motifs are considered primarily as promoters of integrin-mediated cell adhesion. Preclinical studies have demonstrated promising effects of bioprinted constructs on wound healing and tissue organization; however, human evidence for handheld and direct in situ skin bioprinting remains limited, and clinical efficacy has yet to be established in controlled studies. Nevertheless, widespread adoption is hindered by inferior printing fidelity relative to stationary counterparts, a lack of standardized GMP-compliant bioink production, and regulatory ambiguity that impedes clear classification as either medical devices or biologics. Practical barriers, including intraoperative sterility assurance and operator training, also remain unresolved. Looking ahead, we discuss how the convergence of, in particular, artificial intelligence for real-time wound morphometry, closed-loop process control, and smart, self-healing biomaterials promises to surmount these obstacles. We conclude that these synergistic innovations may propel handheld bioprinters from experimental prototypes toward clinical tools with the potential to reshape reconstructive surgery and emergency wound care, although their clinical value will require validation in appropriately designed human studies. Full article

Three-dimensional (3D) bioprinting is an evolving biofabrication approach in regenerative medicine with the potential to overcome many limitations of conventional reconstructive techniques, including donor-site morbidity, limited tissue availability, and suboptimal restoration of form and function. Recent advances in biofabrication have accelerated the development of patient-specific living constructs for reconstructive applications. This narrative review synthesizes contemporary evidence on the use of 3D bioprinting in reconstructive surgery, emphasizing developments most relevant to plastic surgery. The current literature on bioprinting technologies, bioinks, tissue-specific applications, translational studies, and regulatory considerations was critically reviewed. Significant progress has been achieved in the bioprinting of skin, cartilage, bone, osteochondral tissues, vascularized constructs, and composite craniofacial tissues. Advances in extrusion-, inkjet-, laser-, and stereolithography-based printing, together with increasingly sophisticated natural and synthetic bioinks, have improved construct fidelity, cellular viability, and tissue-specific functionality. In situ bioprinting, patient-specific computer-aided design, and hybrid biomaterial strategies have further expanded the clinical potential of bioprinted tissues. Despite these advances, major barriers remain, including inadequate vascularization of large constructs, limited mechanical maturation of load-bearing tissues, manufacturing standardization, regulatory uncertainty, and the absence of robust long-term clinical outcomes. Three-dimensional bioprinting is enabling increasingly personalized tissue fabrication, although most applications remain preclinical. Clinical translation will require further advances in biomaterials, vascular engineering, manufacturing standardization, and regulatory science. Full article

Gel-based novel drug delivery systems (NDDS) occupy a mechanistically distinct niche among controlled-release platforms because they decouple three design variablesnetwork cross-link density, continuous-phase polarity, and stimulus sensitivitythat in particulate carriers (liposomes, polymeric nanoparticles) are often interdependent. This critical review synthesizes 102 primary and secondary sources published predominantly between 2010 and 2026 to interrogate, rather than merely catalog, how hydrogels, organogels, aerogels, nanogels, in situ gelling systems, and hydrogel-forming microneedles have been engineered for site-specific pharmacotherapy. Beyond a taxonomic overview, the review quantitatively contrasts formulation parameters sol–gel transition temperatures (typically 32–37 °C for poloxamer 407/188 systems), swelling ratios, mesh sizes, and reported drug-release half-lives across oncology, chronic diabetic wound care, ophthalmic and nasal-to-brain delivery, musculoskeletal (intra-articular) therapy, subunit vaccine depots, periodontal pocket therapy, and glucose-responsive insulin delivery. Particular attention is paid to the mechanistic basis of burst release, the porosity–mechanical-integrity trade-off inherent to interconnected hydrogel networks, and the divergence between preclinical rodent efficacy and the comparatively sparse controlled human trial data available for most gel platforms. The review concludes that while stimuli-responsive and 3D/4D-printed gel architectures have matured substantially as engineering constructs, clinical translation remains bottlenecked less by materials science than by inconsistent characterization standards, unresolved terminal-sterilization compatibility, and a paucity of head-to-head comparative trials against existing standard-of-care formulations. Full article

Nano bioinks have recently emerged as a promising class of biomaterials for advanced bioprinting applications, offering new opportunities in regenerative medicine, controlled drug delivery, and biosensing technologies. These materials are typically developed by integrating nanostructures such as nanoparticles, nanosheets, and nanofibers into polymeric or hydrogel matrices to enhance mechanical strength, bioactivity, and printing performance. Various fabrication approaches such as direct blending, in-situ polymerization, and surface functionalization are used to incorporate nanomaterials into bioink formulations. Subsequent crosslinking strategies are employed to improve print fidelity and structural stability while maintaining cell viability and biological functionality during the bioprinting process. Despite significant progress in recent years, several challenges continue to hinder the clinical translation of nano bioinks. Achieving consistent batch-to-batch reproducibility, ensuring long-term biocompatibility, and optimizing rheological properties for reliable printing remain critical issues. In addition, regulatory pathways and ethical considerations related to the biomedical use of nano-enabled bioinks are still insufficiently addressed in the literature. This review provides a comprehensive overview of recent advances in the design and fabrication of nano bioinks, highlighting key synthesis strategies, functional nanomaterials used in bioink formulations, and their emerging applications in tissue engineering, drug delivery, and biosensing. Furthermore, the review discusses the major technical, regulatory, and translational challenges that need to be addressed to facilitate the safe and effective implementation of nano bioinks in future biomedical 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

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

Carbon quantum dots (CQDs) and stimuli-responsive hydrogels are advanced functional materials whose hybridization yields CQD-enhanced stimuli-sensitive hydrogels, opening new interdisciplinary avenues for smart material applications. This review systematically summarizes the latest advances in these composites, focusing on synthetic strategies, structure–property modulation mechanisms, and practical applications. Distinct from existing reviews that either investigate CQDs or hydrogels independently or discuss their composites in a single research field, this work features core novelties in integration strategy, application scope and critical analysis: it systematically compares the advantages, limitations and applicable scenarios of three typical CQD–hydrogel integration approaches (physical entrapment, in situ synthesis, covalent conjugation), comprehensively covers the multi-field application progress of the composites and conducts in-depth cross-field analysis of their common scientific issues and technical bottlenecks. By incorporating CQDs, the composites achieve remarkable performance optimizations: 40% improved mechanical toughness, sub-ppm-level heavy metal-sensing sensitivity, and over 80% organic dye photocatalytic degradation efficiency, addressing pure hydrogels’ inherent limitations of insufficient strength and single functionality. These enhancements enable sophisticated applications in biomedical field (real-time biosensing, controlled drug delivery), environmental remediation (pollutant detection/degradation), energy storage, and flexible electronics. The synergistic interplay between CQDs and hydrogels facilitates precise single/multi-stimulus responsiveness (pH, temperature, light), a pivotal advance for precision medicine and intelligent environmental monitoring. Despite promising progress, the large-scale practical application of CQD–hydrogel composites still faces prominent challenges: the difficulty in scalable fabrication with the uniform dispersion of CQDs in hydrogel matrices, poor long-term stability of most composites under physiological cyclic stress (service life < 6 months in practical tests), and low accuracy in discriminating multi-stimuli in complex real-world matrices. Future research should prioritize biomass-based eco-friendly CQD synthesis, machine learning-aided multimodal responsive systems, and 3D bioprinting for scalable manufacturing. Full article

Chronic wounds represent a significant global healthcare challenge, affecting millions of patients and imposing substantial economic burdens on healthcare systems. Traditional wound management approaches often fail to address the complex pathophysiology underlying chronic wounds, including persistent inflammation, impaired angiogenesis, and disrupted extracellular matrix remodeling. Three-dimensional (3D) bioprinting has emerged as a transformative technology that enables the fabrication of patient-specific, biomimetic tissue constructs capable of addressing these intricate challenges. This comprehensive review synthesizes recent advances in 3D bioprinting for chronic wound treatment, examining bioprinting technologies, biomaterial innovations, mechanisms of wound healing, and clinical applications. Recent studies demonstrate that bioprinted constructs incorporating living cells, growth factors, and bioactive molecules can significantly accelerate wound closure, enhance vascularization, and restore functional skin architecture. Notable innovations include in situ bioprinting systems, photosynthetic scaffolds for oxygen delivery, and immunomodulatory bioinks. While significant technical challenges remain—including vascularization, scalability, and regulatory approval—the integration of advanced bioprinting techniques with regenerative medicine principles offers unprecedented opportunities for personalized chronic wound care and improved patient outcomes. Full article

Three-dimensional (3D) bioprinting provides new options for airway reconstruction by enabling the fabrication of customizable, biodegradable scaffolds designed to support in situ tissue regeneration. Building on our established large-animal platform, in which two cm bioprinted tracheal grafts combined with refined surgical techniques and adjunctive laser intervention have achieved long-term survival exceeding three months, the present study aims to explore long-segment (≥four cm) tracheal transplantation. We evaluated the fabrication feasibility and regeneration patterns of extrusion-based 3D bioprinted polycaprolactone (PCL) tracheal grafts in a porcine model. The grafts were implanted via end-to-end anastomosis with adjunctive mechanical stabilization and followed by serial bronchoscopic surveillance, gross examination, and histological analysis. The two cm PCL tracheal grafts achieved reproducible survival exceeding three months when combined with refined surgical techniques, structured postoperative airway management, and optimized wound coverage. Histological analysis revealed multi-lineage tissue formation—including cartilage, muscle, glands, and epithelium—was observed. Cartilage regeneration followed a staged maturation process, compared to epithelial regeneration, although continuous by 12 weeks, remained developmentally immature. A single long-segment transplantation was explored in a single preliminary case, providing an initial technical observation of feasibility; however, definitive conclusions regarding long-term survival or regeneration cannot be drawn. These findings further characterize regenerative responses in a large-animal model and highlight critical translational barriers—fabrication constraints, airway biomechanics, and delayed epithelial maturation—that require systematic investigation before long-segment tracheal reconstruction can advance toward clinical application. Full article

Additive manufacturing (AM) is increasingly recognized as a critical enabler for sustainable space exploration, offering on-demand fabrication, reduced reliance on Earth-based resupply, and enhanced mission autonomy. Over the past decade, in-space AM has progressed from early polymer extrusion experiments aboard the International Space Station (ISS) to the demonstration of multi-material capabilities involving polymers, metals, ceramics, recycling systems, and in situ resource utilization (ISRU) concepts. This review provides a comprehensive synthesis of AM technologies developed for space applications, with emphasis on demonstrated flight heritage, process behavior under microgravity and vacuum conditions, and materials validated in orbit. The paper surveys major AM process families relevant to space, including fused filament fabrication, directed energy deposition, ceramic stereolithography, bioprinting, and closed-loop recycling systems. Key ISS-based platforms—such as the Additive Manufacturing Facility, Ceramic Manufacturing Module, and Refabricator—are reviewed to assess technological maturity and system-level integration. Materials performance across polymers, metals, ceramics, and regolith-based feedstocks is discussed, highlighting the influence of microgravity, thermal transport, and environmental exposure. By comparing in-space results with terrestrial and reduced-gravity studies, this review identifies consistent trends, critical limitations, and remaining knowledge gaps, providing a structured perspective on the readiness of in-space additive manufacturing for future orbital and deep-space missions. Full article

This work characterizes hybrid hydrogels prepared via the combination of natural and synthetic polymers. By incorporating a biocompatible compound, poly(ethylene glycol) diacrylate (PEGDA, M_n = 400), into alginate and carboxymethyl cellulose (CMC)-based hydrogels, the in situ UV crosslinking of these materials was assessed. A custom direct-write (DW) 3D bioprinter was utilized to prepare hybrid hydrogel constructs and scaffolds. A control sample, which consisted of 4% w/v alginate and 4% w/v CMC, was prepared and evaluated in addition to three PEGDA (4.5, 6.5, and 10% w/v)-containing hybrid hydrogels. Rotational rheology was utilized to evaluate the thixotropic behavior of these materials. Filament fusion tests were employed to generate bilayer constructs of various pore sizes, providing metrics for the printability and diffusion rate of hydrogels post-extrusion. Printability indicates the shape fidelity of pore geometry, whereas diffusion rate represents material spreading after deposition. Curing kinetics of PEGDA-containing hydrogels were evaluated using photo-Differential Scanning Calorimetry (DSC) and photorheology. The Kamal model was fitted to photo-DSC results, enabling an assessment and comparison of the curing kinetics for PEGDA-containing hydrogels. Photorheological results highlight the increase in hydrogel stiffness concomitant with PEGDA content. The range of obtained complex moduli (G*) provides utility for the development of brain, kidney, and heart tissue (620–4600 Pa). The in situ UV irradiation of PEGDA-containing hydrogels improved the shape fidelity of printed bilayers and decreased filament diffusion rates. In situ UV irradiation enabled 10-layer scaffolds with 1 × 1 mm pore sizes to be printed. Ultimately, this study highlights the utility of PEGDA-containing hybrid hydrogels for high-resolution DW 3D bioprinting and potential application toward customizable tissue analogs. Full article

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

Periodontal regeneration remains one of the most demanding challenges in oral bioengineering due to the structural complexity of the periodontium and the inflammatory microenvironment accompanying disease. Conventional surgical and pharmacological therapies often fail to achieve full restoration of bone, ligament and cementum, prompting the development of cell-based and biomaterial-assisted approaches. This review summarizes current advances in cellular technologies for periodontal regeneration, emphasizing the biological rationale, material design and delivery methods shaping next-generation treatments. We discuss stem-cell-based strategies employing periodontal ligament, dental pulp and mesenchymal stem cells, their paracrine and immunomodulatory roles, and how their therapeutic potential is enhanced through integration into engineered scaffolds. Recent progress in hydrogel systems, microspheres, decellularized matrices and 3D bioprinting is analyzed, highlighting how structural cues, bioactive nanoparticles and gene-modified cells enable multi-tissue regeneration. Emerging delivery and biofabrication techniques, from manual seeding to automated and in situ printing, are reviewed as key determinants of clinical translation. The convergence of bioprinting precision, immune-responsive biomaterials and personalized cellular constructs positions periodontal bioengineering as a rapidly maturing field with strong prospects for functional restoration of diseased oral tissues. Full article

Three-dimensional bioprinting holds great promise for tissue engineering, but struggles with fabricating complex curved geometries such as vascular networks. Though precise, traditional Cartesian bioprinters are constrained by linear layer-by-layer deposition along fixed axes, resulting in limitations such as the stair-step effect. Multi-axis robotic bioprinting addresses these challenges by allowing dynamic nozzle orientation and motion along curvilinear paths, enabling conformal printing on anatomically relevant surfaces. Although robotic arms offer lower mechanical precision than CNC stages, accuracy can be enhanced through methods such as vision-based toolpath correction. This study presents a modular multi-axis robotic embedded bioprinting platform that integrates a six-degrees-of-freedom robotic arm, a pneumatic extrusion system, and a viscoplastic support bath. A streamlined workflow combines CAD modeling, CAM slicing, robotic simulation, and automated execution for efficient fabrication. Two case studies validate the system’s ability to print freeform surfaces and vascular-inspired tubular constructs with high fidelity. The results highlight the platform’s versatility and potential for complex tissue fabrication and future in situ bioprinting applications. Full article

Cartilage injuries, due to their limited regenerative capacity, often result in chronic pain and functional impairment. These injuries are difficult to manage with conventional surgical repair techniques; therefore, alternative treatments are necessary. Gelatin methacrylate (GelMA) has emerged as a promising biomaterial for cartilage tissue engineering due to its biocompatibility, tunable mechanical properties, and ability to be used in advanced applications like 3D bioprinting. This review examines the synthesis, properties, and limitations of GelMA in cartilage repair, focusing on its applications in 3D bioprinting for the creation of patient-specific cartilage constructs. It also highlights preclinical studies exploring the potential of GelMA-based scaffolds in various animal models. Despite its advantages, challenges remain, such as the mechanical limitations of GelMA and its degradation rate in dynamic environments. Hybrid scaffolds, in situ bioprinting, and personalized bioinks offer solutions to these issues. Ultimately, long-term clinical trials are needed to assess the durability and efficacy of GelMA-based scaffolds in human applications. Future research is aimed at overcoming these challenges, improving the mechanical strength of GelMA scaffolds, and enhancing their clinical translation for cartilage repair. Full article