Search Results (133)

Advancements in bioinks and three-dimensional (3D) printing and bioprinting have significantly advanced cardiovascular tissue engineering by enabling the fabrication of biomimetic cardiac and vascular constructs. Traditional 3D printing has contributed to the development of acellular scaffolds, vascular grafts, and patient-specific cardiovascular models that support surgical planning and biomedical applications. In contrast, 3D bioprinting has emerged as a transformative biofabrication technology that allows for the spatially controlled deposition of living cells and biomaterials to construct functional tissues in vitro. Bioinks—derived from natural biomaterials such as collagen and decellularized matrix, synthetic polymers such as polyethylene glycol (PEG) and polycaprolactone (PCL), or hybrid combinations—have been engineered to replicate extracellular environments while offering tunable mechanical properties. These formulations ensure biocompatibility, appropriate mechanical strength, and high printing fidelity, thereby maintaining cell viability, structural integrity, and precise architectural resolution in the printed constructs. Advanced bioprinting modalities, including extrusion-based bioprinting (such as the FRESH technique), droplet/inkjet bioprinting, digital light processing (DLP), two-photon polymerization (TPP), and melt electrowriting (MEW), enable the fabrication of complex cardiovascular structures such as vascular patches, ventricle-like heart pumps, and perfusable vascular networks, demonstrating the feasibility of constructing functional cardiac tissues in vitro. This review highlights the respective strengths of these technologies—for example, extrusion’s ability to print high-cell-density bioinks and MEW’s ultrafine fiber resolution—as well as their limitations, including shear-induced cell stress in extrusion and limited throughput in TPP. The integration of optimized bioink formulations with appropriate printing and bioprinting platforms has significantly enhanced the replication of native cardiac and vascular architectures, thereby advancing the functional maturation of engineered cardiovascular constructs. Full article

The development of materials engineering allows for the creation of new materials intended for 3D printing, which has become a key tool in tissue engineering, particularly in bone tissue engineering, enabling the production of implants, defect fillers, and scaffolds tailored to the individual needs of patients. Among the wide range of available biomaterials, thermoplastic polymers such as polycaprolactone (PCL), polylactic acid (PLA), polyether ether ketone (PEEK), and polymethyl methacrylate (PMMA) are of significant interest due to their biocompatibility, processability, and variable degradation profiles. This review compiles the latest reports on the applications, advantages, limitations, and modifications in bone tissue engineering. It highlights that PCL and PLA are promising for temporary, resorbable scaffolds, while PEEK and PMMA are suitable for permanent or load-bearing implants. The inclusion of ceramic phases is frequently used to enhance bioactivity. A growing trend can be observed toward developing customized, multifunctional materials that support bone regeneration and biological integration. Despite ongoing progress, the biocompatibility and long-term safety of these materials still require further clinical validation. Full article

Three-dimensional printed polycaprolactone (PCL) tissue engineering scaffolds have drawn increasing interest from the medical industry due to their excellent biocompatibility and biodegradability, yet PCL’s poor mechanical performance has limited their applications. This study introduces a biocompatible and biodegradable polylactic acid (PLA) fiber reinforced PCL (PLA/PCL) composite as the filament for 3D printed scaffolds to significantly enhance their mechanical performance: Special-made PLA short fiber mat was infused with PCL matrix and rolled into PLA/PCL filaments through a “Vacuum Assisted Resin Infusion” (VARI) process. The investigation revealed that the PLA fibers are highly oriented along the printing direction when using this filament for 3D printing due to the unique microstructure formed during the VARI process. At the same PLA fiber content, the percentage increase in Young’s modulus of the 3D printed strands using the filaments produced by the VARI process is 127.6% higher than the 3D printed strands using the filaments produced by the conventional melt blending process. The 3D printed tissue engineering scaffolds using the PLA/PCL composite filament with 11 wt% PLA fiber content also achieved an exceptional 84.2% and 143.3% increase in peak load and stiffness compared to the neat PCL counterpart. Full article

Poly(ε-caprolactone) (PCL) is a synthetic plastic known for its excellent physicochemical properties and a wide range of applications in packaging, coatings, foaming, and agriculture. In medicine, its versatility allows it to function as a scaffold for drug delivery, sutures, implants, tissue engineering, and 3D printing. In addition to its biocompatibility, PCL’s most notable characteristic is its biodegradability. However, this property is affected by temperature, microbial activity, and environmental conditions, which means PCL can sometimes remain in nature for long periods. This review shows that various types of microorganisms can efficiently degrade PCL, including different strains of Pseudomonas spp., Streptomyces spp., Alcaligenes faecalis, and fungi like Aspergillus oryzae, Fusarium spp., Rhizopus delemar, and Thermomyces lanuginosus. These microorganisms produce enzymes such as lipases, esterases, and cutinases that break down PCL into smaller molecules that act as substrates. The review also examines the phylogenetic diversity of organisms capable of biodegrading PCL, the biochemical pathways involved in this process, and specific aspects of the genetic framework responsible for the expression of the enzymes that facilitate degradation. Targeted research on microbial PCL biodegradation and its practical applications could significantly aid in reducing and managing plastic waste on a global ecological scale. Full article

Direct ink writing (DIW) is an attractive, extrusion-based, additive manufacturing method for fabricating scaffold structures with controlled porosity using custom composite inks. Polycaprolactone–bioactive glass (PCL-BG) inks have gained attention for bone applications, but optimizing the formulation and fabrication of PCL-BG-based inks for improved printability and desired mechano-biological properties remains a challenge. This study employs a two-step design to systematically evaluate the effect of three factors in terms of PCL-BG composite printability and mechano-biological properties: ink preparation (acetone or dichloromethane (DCM) as the solvent, and mechanical compounding), the extrusion temperature (90 °C, 110 °C, and 130 °C), and the BG content (0%, 10%, and 20% BG). Pure PCL was used as the control. Rheological, calorimetric, and thermo-gravimetric analyses were conducted before printing. Cylindrical scaffolds and solid wells were printed to evaluate the printability, mechanical properties, and cytocompatibility. The scaffold porosity and pore size were carefully examined. Mechanical tests demonstrated that composite formulations with added BG and higher printing temperatures increased the elastic modulus and yield strength. However, PCL-DCM-BG combinations exhibited increased brittleness with higher BG content. Despite concerns about the toxic solvent DCM, the cytocompatibility was comparable to pure PCL for all ink preparation methods. The results suggest that the interaction between the ink preparation solvent, the BG content, and the printing temperature is critical for material design and fabrication planning in bone tissue engineering applications, providing insights into optimizing PCL-BG composite ink formulations for 3D printing in bone tissue engineering. Full article

The increasing demand for orthopedic and neurosurgical implants has driven advancements in biomaterials, additive manufacturing, and antimicrobial strategies. With an increasingly aging population, and a high incidence of orthopedic trauma in developing countries, the need for effective, biocompatible, and infection-resistant implants is more critical than ever. This review explores the role of polymers in 3D printing for medical applications, focusing on their use in orthopedic and neurosurgical implants. Polylactic acid (PLA), polycaprolactone (PCL), and polyetheretherketone (PEEK) have gained attention due to their biocompatibility, mechanical properties, and potential for antimicrobial modifications. A major challenge in implantology is the risk of periprosthetic joint infections (PJI) and surgical site infections (SSI). Current strategies, such as antibiotic-loaded polymethylmethacrylate (PMMA) spacers and bioactive coatings, aim to reduce infection rates, but limitations remain. Additive manufacturing enables the creation of customized implants with tailored porosity for enhanced osseointegration while allowing for the incorporation of antimicrobial agents. Future perspectives include the integration of artificial intelligence for implant design, nanotechnology for smart coatings, and bioresorbable scaffolds for improved bone regeneration. Advancing these technologies will lead to more efficient, cost-effective, and patient-specific solutions, ultimately reducing infection rates and improving long-term clinical outcomes. Full article

The field of tissue engineering increasingly demands accurate predictive models to optimize the 3D printing process of bio-scaffolds. This study presents a unified numerical model that predicts extrusion velocity and strut diameter based on printing conditions and the material properties of polycaprolactone (PCL) and dimethyl sulfone (DMSO₂) composites. The extrusion velocity was simulated using Navier–Stokes equations, while the strut diameter was calculated via a surface energy model. For PCL, the extrusion velocity showed a temperature coefficient of 23.3%/°C and a pressure coefficient of 19.1% per 100 kPa; the strut diameter exhibited a temperature coefficient of 21.6%/°C and a pressure coefficient of 16.6% per 100 kPa. When blended with DMSO₂, the lower viscosity and higher surface energy resulted in increased extrusion velocity and strut diameter. The proposed model achieved a high predictive accuracy, with determination coefficient (R²) values exceeding 0.95. These results demonstrate the model’s potential to optimize 3D printing parameters, guide biomaterial selection, and predict pore characteristics, ultimately supporting the rational design of tissue engineering scaffolds. Full article

Tension-free hernioplasty has effectively reduced postoperative recurrence and mitigated complications by employing polymer patches. However, clinically used polymer patches often fall short in terms of the anti-deformation, anti-adhesion, and tissue integration functions, which can result in visceral adhesions and foreign body reactions after implantation. In this study, a Janus three-layer composite patch was developed for abdominal wall defect repair using a combination of 3D printing, electrospraying, and electrospinning technologies. On the visceral side, a dense electrospun polyvinyl alcohol/sodium hyaluronate (PVA/HA) scaffold was fabricated to inhibit cell adhesion. The middle layer, composed of polycaprolactone (PCL), provided mechanical support. On the muscle-facing side, a loose and porous electrospun nanofiber scaffold was created through electrospraying and electrospinning, promoting cell adhesion and migration to facilitate tissue regeneration. Mechanical testing demonstrated that the composite patch possessed excellent tensile strength (23.58 N/cm), surpassing the clinical standard (16 N/cm). Both in vitro and in vivo evaluations confirmed the patch’s outstanding biocompatibility. Compared with the control PCL patch, the Janus composite patch significantly reduced the visceral adhesion and enhanced the tissue repair in animal models. Collectively, this Janus composite patch integrated anti-deformation, anti-adhesion, and tissue-regenerative properties, providing a promising solution for effective abdominal wall defect repair. Full article

A novel bi-layered scaffold, obtained via 3D printing and electrospinning, was designed to improve osteochondral region reconstruction. The upper electrospun membrane will act as a barrier against unwanted tissue infiltration, while the lower 3D-printed layer will provide a porous structure for tissue ingrowth. Graphene was integrated into the scaffold for its antibacterial properties, and the drug Osteogenon^® (OST) was added to promote bone tissue regeneration. The composite scaffolds were subjected to comprehensive physical, thermal, and mechanical evaluations. Additionally, their biological functionality was assessed by means of NHAC-kn cells. The 0.5% graphene addition to PCL significantly increased strain at break, enhancing the material ductility. GNP also acted as an effective nucleating agent, raising crystallization temperatures and supporting mineralization. The high surface area of graphene facilitated rapid apatite formation by attracting calcium and phosphate ions. This was confirmed by FTIR, µCT and SEM analyses, which highlighted the positive impact of graphene on mineral deposition. The synergistic interaction between graphene nanoplatelets and Osteogenon^® created a bioactive environment that enhanced cell adhesion and proliferation, and promoted superior apatite formation. These findings highlight the scaffold’s potential as a promising biomaterial for osteochondral repair and regenerative medicine. Full article

Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating scaffolds, osteogenic cells, and bioactive factors to regenerate functional bone. This systematic review evaluates BTE strategies for mandibular reconstruction, focusing on critical-sized defects in large animal models and their translational potential for clinical applications. Methods: A systematic review was performed following PRISMA guidelines. Eligible studies involved large animal models and critical-sized mandibular defects treated with at least two BTE components (scaffold, osteogenic cells, or growth factors). Quality and bias assessments were conducted using ARRIVE guidelines and SYRCLE tools. Results: Of the 6088 studies screened, 27 met the inclusion criteria, focusing on critical-sized mandibular defects in large animal models such as pigs, sheep, and dogs. Common scaffolds included β-tricalcium phosphate (β-TCP), poly-lactic-co-glycolic acid (PLGA), and polycaprolactone (PCL), frequently combined with bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors like recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical outcomes demonstrated effective bone regeneration, vascularization, and biomechanical restoration. Advanced strategies, including in vivo bioreactors and 3D-printed scaffolds, further enhanced regeneration. However, challenges such as incomplete scaffold degradation, hypoxic conditions within constructs, and variability in growth factor efficacy and dose optimization were observed, emphasizing the need for further refinement to ensure consistent outcomes. Conclusions: BTE shows promise in mandibular reconstruction, achieving bone regeneration and functional restoration in preclinical models of critical-sized defects. However, challenges such as scaffold optimization, vascularization enhancement, and protocol standardization require further investigation to facilitate clinical translation. These findings emphasize the need for refinement to achieve consistent, scalable outcomes for clinical use. Full article

The limitations of traditional, autologous bone grafts, such as the scarcity of donor material and the risks of secondary surgical trauma, have spurred the development of alternatives for the repair of large bone defects. Bionic bone scaffolds fabricated via fused deposition modeling (FDM)—a three-dimensional (3D) printing technique—are considered promising. While gyroid-structured scaffolds mimic the complex micro-architecture of cancellous bone, their application in FDM 3D printing remains understudied. Furthermore, no consensus has been reached on the ideal pore size for gyroid scaffolds, which is influenced by the infill density. In this study, we fabricated five groups of polycaprolactone/hydroxyapatite (PCL/HA) scaffolds with different infill densities (40%, 45%, 50%, 55%, and 60%) using a solvent-free filament preparation method. Scanning electron microscopy (SEM) observation showed that all scaffolds exhibit an interconnected porous structure. The scaffold with the 55% infill density, featuring a pore size of 465 ± 63 μm, demonstrated optimal hydrophilicity and mechanical properties comparable to natural cancellous bone. In addition, this scaffold supported cellular bridging within its pores and showed the highest alkaline phosphatase (ALP) activity and calcium salt deposition. Our findings offer novel insights into the design of gyroid-like scaffolds and their fabrication via FDM, paving the way for potential clinical applications. Full article

Orthopedic soft tissue injuries, such as those to the fibrocartilaginous meniscus in the knee, present a significant clinical challenge, impacting millions globally and often requiring surgical interventions that fail to fully restore mechanical function. Current bioengineered meniscal replacement options that incorporate synthetic and/or natural scaffolds have limitations in biomechanical performance and biological integration. This study introduces a novel scaffold fabrication approach, termed Hybrid Hydrogels Augmented via Additive Network Integration (HANI) with great potential for meniscal tissue engineering applications. HANI scaffolds combine cross-linked gelatin-based hydrogels with polycaprolactone (PCL) additive networks, created via Fused Deposition Modeling (FDM), to enhance mechanical strength and replicate the anisotropic properties of the meniscus. Custom Stereolithography (SLA)-printed molds ensure precise dimensional control and seamless incorporation of PCL networks within the hydrogel matrix. The mechanical evaluation of HANI scaffolds showed improvements in compressive stiffness, stress relaxation behavior, and load-bearing capacity, especially with circumferential and 3D PCL reinforcements, when compared to hydrogel scaffolds without additive networks. These findings highlight HANI’s potential as a cost-effective, scalable, and tunable scaffold fabrication approach for meniscal tissue engineering applications. Full article

Background/Objectives: Meniscus injuries represent a critical challenge in orthopedic medicine due to the limited self-healing capacity of the tissue. This study presents the development and characterization of polycaprolactone/graphene oxide (PCL/GO) scaffolds fabricated using 3D bioprinting technology for meniscus cartilage regeneration. Methods: GO was incorporated at varying concentrations (1%, 3%, 5% w/w) to enhance the bioactivity, mechanical, thermal, and rheological properties of PCL scaffolds. Results: Rheological analyses revealed that GO significantly improved the storage modulus (G’) from 36.1 Pa to 97.1 Pa and the yield shear stress from 97.2 Pa to 507.1 Pa, demonstrating enhanced elasticity and flow resistance. Mechanical testing showed that scaffolds with 1% GO achieved an optimal balance, with an elastic modulus of 614 MPa and ultimate tensile strength of 46.3 MPa, closely mimicking the native meniscus’s mechanical behavior. FTIR analysis confirmed the successful integration of GO into the PCL matrix without disrupting its chemical integrity, while DSC analysis indicated improved thermal stability, with increases in melting temperatures. SEM analysis demonstrated a roughened surface morphology conducive to cellular adhesion and proliferation. Fluorescence microscopy using DAPI staining revealed enhanced cell attachment and regular nuclear distribution on PCL/GO scaffolds, particularly at lower GO concentrations. Antibacterial assays exhibited larger inhibition zones against E. coli and S. aureus, while cytotoxicity tests confirmed the biocompatibility of the PCL/GO scaffolds with fibroblast cells. Conclusions: This study highlights the potential of PCL/GO 3D-printed scaffolds as biofunctional platforms for meniscus tissue engineering, combining favorable mechanical, rheological, biological, and antibacterial properties. Full article

Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu²⁺ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications. Full article

In the last thirty years, tissue engineering (TI) has emerged as an alternative method to regenerate tissues and organs and restore their function by implanting specific lineage cells, growth factors, or biomolecules functionalizing a matrix scaffold. Recently, several pathologies have led to bone loss or damage, such as malformations, bone resorption associated with benign or malignant tumors, periodontal disease, traumas, and others in which a discontinuity in tissue integrity is observed. Bone tissue is characterized by different stiffness, mechanical traction, and compression resistance as a function of the different compartments, which can influence susceptibility to injury or destruction. For this reason, research into repairing bone defects began several years ago to find a scaffold to improve bone regeneration. Different techniques can be used to manufacture 3D scaffolds for bone tissue regeneration based on optimizing reproducible scaffolds with a controlled hierarchical porous structure like the extracellular matrix of bone. Additionally, the scaffolds synthesized can facilitate the inclusion of bone or mesenchymal stem cells with growth factors that improve bone osteogenesis, recruiting new cells for the neighborhood to generate an optimal environment for tissue regeneration. In this review, current state-of-the-art scaffold manufacturing based on the use of polycaprolactone (PCL) as a biomaterial for bone tissue regeneration will be described by reporting relevant studies focusing on processing techniques, from traditional—i.e., freeze casting, thermally induced phase separation, gas foaming, solvent casting, and particle leaching—to more recent approaches, such as 3D additive manufacturing (i.e., 3D printing/bioprinting, electrofluid dynamics/electrospinning), as well as integrated techniques. As a function of the used technique, this work aims to offer a comprehensive overview of the benefits/limitations of PCL-based scaffolds in order to establish a relationship between scaffold composition, namely integration of other biomaterial phases’ structural properties (i.e., pore morphology and mechanical properties) and in vivo response. Full article