Search Results (53)

The increasing demand for novel tissue engineering (TE) applications in bone tissue regeneration underscores the importance of exploring advanced manufacturing techniques and biomaterials for personalised treatment approaches. Three-dimensional printing (3DP) technology facilitates the development of implantable devices with intricate geometries, enabling patient-specific therapeutic solutions. Although Fused Filament Fabrication (FFF) and Direct Ink Writing (DIW) are widely utilised for fabricating bone-like implants, the need for multiple processing steps often prolongs the overall production time. In this study, a single-step melt-extrusion 3DP technique was performed to develop multi-material scaffolds including bioceramics, hydroxyapatite (HA), and β-tricalcium phosphate (TCP) in both their bioactive and calcined forms at 10% and 20% w/w, within polycaprolactone (PCL) matrices. Printing parameters were optimised, and physicochemical properties of all biomaterials and final forms were evaluated. Thermal degradation and surface morphology analyses assessed the consistency and distribution of the ceramics across the different formulations. The tensile testing of the scaffolds defined the impact of each ceramic type and wt% on scaffold flexibility performance, while in vitro cell studies determined the cytocompatibility efficiency. Hence, all 3D-printed PCL–ceramic composite scaffolds achieved structural integrity and physicochemical and thermal stability. The mechanical profile of extruded samples was relevant to the ceramic consistency, providing valuable insights for further mechanotransduction investigations. Notably, all materials showed high cell viability and proliferation, indicating strong biocompatibility. Therefore, this additive manufacturing (AM) process is a precise and fast approach for developing biomaterial-based scaffolds, with potential applications in surgical restoration and support of segmental bone defects. Full article

Nanoscale amorphous calcium phosphate (ACP) exhibits superior bioactivity, degradability, and osteoblast adhesion compared to hydroxyapatite (HAp), making it a promising bioactive ceramic material for bone regeneration applications. This study explores the integration of ACP as a bioactive additive in polylactic acid/polycaprolactone (PLA/PCL) composites. Nanoscale ACP powder was synthesized through low-temperature wet chemical methods without additional reagents. The composite, consisting of 10 wt.% ACP, 80 wt.% PLA, and 20 wt.% PCL, achieved optimal tensile strength (>12 MPa) and elongation (>0.1%). Utilizing the Taguchi experimental design, the microinjection molding parameters were optimized, and they are a material temperature of 190 °C, an injection speed of 50 mm/s, and a holding pressure speed of 30 mm/s. Variance analysis identified the injection speed to be the most significant factor, contributing 50.73% to the overall effect. Immersing ACP in simulated body fluid (SBF) for six hours reduced its calcium ion concentration by 28%, with this concentration stabilizing thereafter. Biocompatibility was confirmed through an MTT assay with NIH-3T3 cells, demonstrating the PLA/PCL/ACP composite’s compatibility. Bone differentiation and mineralization tests showed the enhanced performance of both ACP and the composite material. Degradation tests indicated an initial 0.29% weight increase in the first week, followed by a 2% reduction by the fifth week. These results underscore the PLA/PCL/ACP composite’s excellent mechanical properties, biocompatibility, and suitability for injection molding, positioning it as a strong candidate for biodegradable bone screw applications. Full article

In this study, the microinjection molding technology was adopted to prepare polylactic acid (PLA)/polycaprolactone (PCL)/bioactive glass (BG) composites with varying BG contents for biomedical applications. The various measurement techniques, including scanning electronic microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, the water contact angle (WCA) test, the mechanical test, and in vitro biological evaluations, were applied to characterize the above interesting biocomposites. The experimental results show that the extremely strong shear force field generated during the microinjection molding process could induce the in situ formation of micron PCL dispersed phase fibril structures and strongly promote the homogeneous dispersion of micron BG filler particles in the PLA/PCL polymer matrix, which therefore leads to a significant improvement in the specific mechanical property of the PLA/PCL/BG composite. For example, with BG fillers content increasing to 10 wt%, the Young’s modulus of the above obtained PLA/PCL/BG composite could reach 2122.9 MPa, which is 1.47 times higher than that of the unfilled PLA/PCL blend material. In addition, it is also found that under the simulated body fluid (SBF) environment, the incorporated BG fillers in the PLA/PCL polymer matrix could be effectively transformed into hydroxyapatite (HA) components on the treated sample surface, thus being greatly advantageous to enhancing the material’s in vitro bioactivity. Obviously, the microinjection molded PLA/PCL/BG biocomposites could exhibit excellent comprehensive performance, revealing that the microinjection molding processing method could hold great potential in industrialization applications of the resulting biodegradable biomedical materials. 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

Bone grafts are commonly used in orthopedic and dental surgeries to facilitate bone repair and regeneration. A new type of bone graft, polycaprolactone-infiltrated three dimensionally printed hydroxyapatite (3DP HA/PCL), was previously developed by infiltrating polycaprolactone (PCL) into preformed three-dimensional-printed hydroxyapatite (3DP HA) that was fabricated using binder jetting technology combined with a low-temperature phase transformation process. However, when producing small granules, which are often used for bone grafting, issues of granule agglomeration emerged, complicating the application of this method. This study aimed to develop a fabrication process for 3DP HA/PCL bone graft granules using solution infiltration and liquid agitation. The effects of varying PCL solution concentrations (40% and 50% w/w) and different agitating liquids (deionized water or DI, N-Methyl-2-Pyrrolidone or NMP, and an NMP-DI mixture) on the properties of the resulting composites were investigated. XRD and FTIR analysis confirmed the coexistence of HA and PCL within the composites. The final PCL content was comparable across all conditions. The contact angles of 3DP HA/PCL were 26.3 and 69.8 degree for 40% and 50% PCL solution, respectively, when using DI, but were zero when using NMP and NMP-DI. The highest compression load resistance and diametral tensile strength were achieved using the 50% PCL solution with DI or the NMP-DI mixture. DI resulted in a dense PCL coating, while NMP and the NMP-DI mixture produced a porous and irregular surface morphology. All samples exhibited a porous internal microstructure due to PCL infiltration into the initial pores of the 3D-printed HA. Biocompatibility tests showed that all samples supported the proliferation of MC3T3-E1 cells, with the greatest OD values observed for the 50% PCL solution with DI or the NMP-DI mixture at each cultured period. Considering the microstructural, mechanical, and biological properties, the 50% PCL solution with the NMP-DI mixture demonstrated overall desirable properties. Full article

Polycaprolactone (PCL) is a biodegradable polyester that might be used in tissue engineering to obtain scaffolds for bone reconstruction using 3D-printing technologies. New material compositions based on PCL, with improved physicochemical properties and excellent biocompatibility, would improve its applicability in bone regeneration. The aim of this study was to assess the potential toxic effects of PCL-based composite materials containing 5% hydroxyapatite (PCL/SHAP), 5% bioglass (PCL/BIO), or 5% chitosan (PCL/CH) on MG-63 human fibroblast-like cells in vitro. Material tests were carried out using X-ray diffraction, differential thermal analysis/thermal gravimetry, BET specific surface analysis, and scanning electron microscopy. The effect of the biomaterials on the MG-63 cells was then assessed based on toxicity tests using indirect and direct contact methods. The analysis showed that the tested biomaterials did not significantly affect cell morphology, viability, proliferation, or migration. We concluded that biodegradable PCL-based scaffolds may be suitable for tissue scaffold production, and the addition of bioglass improves the growth of cultured cells. Full article

Bone tissue engineering has seen significant advancements with innovative scaffold fabrication techniques such as 3D printing. This review focuses on enhancing polycaprolactone (PCL) scaffold properties through structural modifications, including surface treatments, pore architecture adjustments, and the incorporation of biomaterials like hydroxyapatite (HA). These modifications aim to improve scaffold conformation, cellular behavior, and mechanical performance, with particular emphasis on the role of mesenchymal stem cells (MSCs) in bone regeneration. The review also explores the potential of integrating nanomaterials and graphene oxide (GO) to further enhance the mechanical and biological properties of PCL scaffolds. Future directions involve optimizing scaffold structures and compositions for improved bone tissue regeneration outcomes. Full article

Robust materials in medical applications are sought after and researched, especially for 3D printing in bone tissue engineering. Poly[ε-caprolactone] (PCL) is a commonly used polymer for scaffolding and other medical uses. Its strength is a drawback compared to other polymers. Herein, PCL was mixed with hydroxyapatite (HAp). Composites were developed at various concentrations (0.0–8.0 wt. %, 2.0 step), aiming to enhance the strength of PCL with a biocompatible additive in bioplotting. Initially, pellets were derived from the shredding of filaments extruded after mixing PCL and HAp at predetermined quantities for each composite. Specimens were then manufactured by bioplotting 3D printing. The samples were tested for their thermal and rheological properties and were also mechanically, morphologically, and chemically examined. The mechanical properties included tensile and flexural investigations, while morphological and chemical examinations were carried out employing scanning electron microscopy and energy dispersive spectroscopy, respectively. The structure of the manufactured specimens was analyzed using micro-computed tomography with regard to both their dimensional deviations and voids. PCL/HAp 6.0 wt. % was the composite that showed the most enhanced mechanical (14.6% strength improvement) and structural properties, proving the efficiency of HAp as a reinforcement filler in medical applications. Full article

The objective of this investigation was to fabricate a photothermally responsive composite bone scaffold aimed at facilitating bone tissue regeneration and remedying bone defects via mild thermal stimulation. The photothermal-sensitive nanomaterial SiO₂ coated Fe₃O₄ (SiO₂@Fe₃O₄), synthesized through the hydrolysis–condensation process of tetraethyl orthosilicate (TEOS), displayed a uniform distribution of SiO₂ coating, effectively preventing the aggregation of Fe₃O₄ particles within the scaffold matrix. The composite scaffold containing 5% mass fraction of photothermal-sensitive nanoparticles exhibited evenly dispersed microstructural porosity, a compressive strength of 5.722 MPa, and a water contact angle of 58.3°, satisfying the mechanical property requisites of cancellous bone while demonstrating notable hydrophilic characteristics. Upon exposure to near-infrared light at ambient temperature, the 5% composite scaffold underwent a temperature elevation of 3–6 °C within 40–45 s, attaining a temperature range (40–43 °C) conducive to fostering osteogenic differentiation. Experimental findings validated that the SiO₂@Fe₃O₄/polyvinyl alcohol (PVA)/hydroxyapatite (HA)/polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) bone scaffold showcased outstanding mechanical and photothermal attributes, thereby presenting a pioneering avenue for advancing bone tissue cell proliferation and addressing bone defect rehabilitation. Full article

Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone–hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future. Full article

Hydroxyapatite/polycaprolactone (HA/PCL) composites have been extensively explored in laser powder bed fusion (L-PBF) for bone tissue engineering. However, conventional mechanical mixing methods for preparing composite powders often yield inhomogeneous compositions and suboptimal flowability. In this study, HA/PCL powders were prepared and optimized for L-PBF using the modified emulsion solvent evaporation method. The morphology, flowability and thermal and rheological properties of the powders were systematically investigated, along with the mechanical and biological properties of the fabricated specimens. The HA/PCL powders exhibited spherical morphologies with a homogeneous distribution of HA within the particles. The addition of small amounts of HA (5 wt% and 10 wt%) enhanced the processability and increased the maximum values of the elastic modulus and yield strength of the specimens from 129.8 MPa to 166.2 MPa and 20.2 MPa to 25.1 MPa, respectively, while also improving their biocompatibility. However, excessive addition resulted in compromised sinterability, thereby affecting both mechanical and biological properties. Full article

Nano-hydroxyapatite (HAp) is an ideal material in the field of biomedicine due to its good biocompatibility and bioactivity. However, a significant drawback of pure HAp materials is their inferior mechanical properties. Therefore, in this rigorous investigation, the optimal calcium-to-phosphorus ratio for the synthesis of HAp was meticulously delineated, followed by its nuanced modification using KH550 (γ-aminopropyltriethoxysilane). This was further amalgamated with polycaprolactone (PCL) with the aim of providing a superior material alternative within the domain of bone scaffold materials. The post-modified HAp demonstrated enhanced interfacial compatibility with PCL, bestowing the composite with superior mechanical characteristics, notably a peak bending strength of 6.38 ± 0.037 MPa and a tensile strength of 3.71 ± 0.040 MPa. Scanning electron microscope (SEM) imagery revealed an intriguing characteristic of the composite: an initial ascension in porosity upon HAp integration, subsequently followed by a decline. Beyond this, the composite not only exhibited stellar auto-degradation prowess but also realized a sustained release cycle of 24 h, markedly optimizing drug utility efficiency. A kinetic model for drug dispensation was developed, positing an adherence to a pseudo-second-order kinetic principle. In tandem, through the formulation of an intra-particle diffusion model, the diffusion mechanisms pre- and post-modification were deeply probed. Cytotoxicity assays underscored the composite’s exemplary biocompatibility. Such findings accentuate the vast potential of the modified HAp–PCL composite in bone tissue engineering, heralding a novel and efficacious avenue for impending bone defect amelioration. Full article

Calcium phosphate cements present increased biocompatibility due to their chemical composition being similar to that of the hydroxyapatite in the hard tissues of the living body. It has certain limitations due to its poor mechanical properties, such as low tensile strength and increased brittleness. Thus, the optimal way to improve properties is through the design of novel composite cements. The purpose was fulfilled using a 25% hydroxyethyl methacrylate (HEMA) mixed with 3% urethane dimethacrzlate (UDMA) base matrix with various ratios of polyethylene glycol (PEG 400) and polycaprolactone (PCL). Mineral filler is based on tricalcium phosphate (TCP) with different chitosan ratio used as bio-response enhancer additive. Four mixtures were prepared: S0—unfilled polymer matrix; S1 with 50% TCP filler; S2 with 50% chitosan + TCP filler; and S3 with 17.5% chitosan + TCP mixed with 17.5% nano hydroxyapatite (HA). The mechanical properties testing revealed that the best compressive strength was obtained by S2, followed by S3, and the worst value was obtained for the unfilled matrix. The same tendency was observed for tensile and flexural strength. These results show that the novel filler system increases the mechanical resistance of the TCP composite cements. Liquid exposure investigation reveals a relative constant solubility of the used filler systems during 21 days of exposure: the most soluble fillers being S3 and S2 revealing that the additivated TCP is more soluble than without additives ones. Thus, the filler embedding mode into the polymer matrix plays a key role in the liquid absorption. It was observed that additive filler enhances the hydrophobicity of UDMA monomer, with the matrix resulting in the lowest liquid absorption values, while the non-additivated samples are more absorbent due to the prevalence of hydrolytic aliphatic groups within PEG 400. The higher liquid absorption was obtained on the first day of immersion, and it progressively decreased with exposure time due to the relative swelling of the surface microstructural features. The obtained results are confirmed by the microstructural changes monitored by SEM microscopy. S3 and S2 present a very uniform and compact filler distribution, while S1 presents local clustering of the TCP powder at the contact with the polymer matrix. The liquid exposure revealed significant pore formation in S0 and S1 samples, while S3 and S2 proved to be more resistant against superficial erosion, proving the best resistance against liquid penetration. Full article

The development of advanced biomaterials and manufacturing processes to fabricate biologically and mechanically appropriate scaffolds for bone tissue is a significant challenge. Polycaprolactone (PCL) is a biocompatible and degradable polymer used in bone tissue engineering, but it lacks biofunctionalization. Bioceramics, such as hydroxyapatite (HA) and β tricalcium phosphate (β-TCP), which are similar chemically to native bone, can facilitate both osteointegration and osteoinduction whilst improving the biomechanics of a scaffold. Carbon nanotubes (CNTs) display exceptional electrical conductivity and mechanical properties. A major limitation is the understanding of how PCL-based scaffolds containing HA, TCP, and CNTs behave in vivo in a bone regeneration model. The objective of this study was to evaluate the use of three-dimensional (3D) printed PCL-based composite scaffolds containing CNTs, HA, and β-TCP during the initial osteogenic and inflammatory response phase in a critical bone defect rat model. Gene expression related to early osteogenesis, the inflammatory phase, and tissue formation was evaluated using quantitative real-time PCR (RT-qPCR). Tissue formation and mineralization were assessed by histomorphometry. The CNT+HA/TCP group presented higher expression of osteogenic genes after seven days. The CNT+HA and CNT+TCP groups stimulated higher gene expression for tissue formation and mineralization, and pro- and anti-inflammatory genes after 14 and 30 days. Moreover, the CNT+TCP and CNT+HA/TCP groups showed higher gene expressions related to M1 macrophages. The association of CNTs with ceramics at 10wt% (CNT+HA/TCP) showed lower expressions of inflammatory genes and higher osteogenic, presenting a positive impact and balanced cell signaling for early bone formation. The association of CNTs with both ceramics promoted a minor inflammatory response and faster bone tissue formation. Full article

The firm integration of anterior cruciate ligament (ACL) grafts into bones remains the most demanding challenge in ACL reconstruction, since graft loosening means graft failure. For a functional-tissue-engineered ACL substitute to be realized in future, robust bone attachment sites (entheses) have to be re-established. The latter comprise four tissue compartments (ligament, non-calcified and calcified fibrocartilage, separated by the tidemark, bone) forming a histological and biomechanical gradient at the attachment interface between the ACL and bone. The ACL enthesis is surrounded by the synovium and exposed to the intra-articular micromilieu. This review will picture and explain the peculiarities of these synovioentheseal complexes at the femoral and tibial attachment sites based on published data. Using this, emerging tissue engineering (TE) strategies addressing them will be discussed. Several material composites (e.g., polycaprolactone and silk fibroin) and manufacturing techniques (e.g., three-dimensional-/bio-printing, electrospinning, braiding and embroidering) have been applied to create zonal cell carriers (bi- or triphasic scaffolds) mimicking the ACL enthesis tissue gradients with appropriate topological parameters for zones. Functionalized or bioactive materials (e.g., collagen, tricalcium phosphate, hydroxyapatite and bioactive glass (BG)) or growth factors (e.g., bone morphogenetic proteins [BMP]-2) have been integrated to achieve the zone-dependent differentiation of precursor cells. However, the ACL entheses comprise individual (loading history) asymmetric and polar histoarchitectures. They result from the unique biomechanical microenvironment of overlapping tensile, compressive and shear forces involved in enthesis formation, maturation and maintenance. This review should provide a road map of key parameters to be considered in future in ACL interface TE approaches. Full article