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Bioresorbable chitosan scaffolds have shown potential for osteochondral repair applications. Thein vivodegradation of chitosan, mediated by lysozyme and releasing glucosamine, enables progressive replacement by ingrowing tissue. Here the degradation process of a chitosan-nHA based bioresorbable scaffold was investigated for mass loss, mechanical properties and degradation products released from the scaffold when subjected to clinically relevant enzyme concentrations. The scaffold showed accelerated mass loss during the early stages of degradation but without substantial reduction in mechanical strength or structure deterioration. Although not cytotoxic, the medium in which the scaffold was degraded for over 2 weeks showed a transient decrease in mesenchymal stem cell viability, and the main degradation product (glucosamine) demonstrated a possible adverse effect on viability when added at its peak concentration. This study has implications for the design and biomedical application of chitosan scaffolds, underlining the importance of modelling degradation products to determine suitability for clinical translation.
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Sobrevivência Celular , Quitosana , Teste de Materiais , Células-Tronco Mesenquimais , Engenharia Tecidual , Alicerces Teciduais , Quitosana/química , Sobrevivência Celular/efeitos dos fármacos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/citologia , Animais , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Células Cultivadas , Glucosamina/química , Humanos , Muramidase/química , Implantes AbsorvíveisRESUMO
Internal radiotherapy delivers radioactive sources inside the body, near to or into malignant tumours, which may be particularly effective when malignancies are not responding to external beam radiotherapy. A pure beta emitter, 90Y, is currently used for internal radiotherapy. However, theranostic radionuclide-doped microspheres can be developed by incorporating 153Sm, which emits therapeutic beta and diagnostic gamma energies. This study investigated the production of high concentrations of samarium-content doped phosphate-based glass microspheres. The glass P60 (i.e. 60P2O5-25CaO-15Na2O) was mixed with Sm2O3 at ratios of 75:25 (G75:Sm25), 50:50 (G50:Sm50) and 25:75 (G25:Sm75) and processed via flame spheroidisation. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) confirmed the microsphere uniformity with significantly high samarium content up to 44 % in G25:Sm75. Via X-ray diffraction (XRD) analysis, samarium-doped microspheres appeared to be glass-ceramic in nature. Mass-loss, size and pH changes were performed over 28 days, revealing a significant increase in samarium microsphere stability. After 15 min of neutron activation (neutron flux 3.01 × 1013 n.cm-2.s-1), the specific activity of the microspheres (G75:Sm25, G50:Sm50 and G25:Sm75) was 0.28, 0.54 and 0.58 GBq.g-1, respectively. Therefore, the samarium microspheres produced in this study provide great potential for improving internal radiotherapy treatment for liver cancer by avoiding complex procedures and using less microspheres with shorter irradiation time.
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Neoplasias Hepáticas , Samário , Humanos , Samário/química , Fosfatos , Microesferas , Vidro/químicaRESUMO
Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus.
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Biowastes from agriculture, sewage, household wastes, and industries comprise promising resources to produce biomaterials while reducing adverse environmental effects. This study focused on utilising waste-derived materials (i.e., eggshells as a calcium source, struvite as a phosphate source, and CH3COOH as dissolution media) to produce value-added products (i.e., calcium phosphates (CaPs) derived from biomaterials) using a continuous flow hydrothermal synthesis route. The prepared materials were characterised via XRD, FEG-SEM, EDX, FTIR, and TEM analysis. Magnesium whitlockite (Mg-WH) and hydroxyapatite (HA) were produced by single-phase or biphasic CaPs by reacting struvite with either calcium nitrate tetrahydrate or an eggshell solution at 200 °C and 350 °C. Rhombohedral-shaped Mg-WH (23-720 nm) along with tube (50-290 nm diameter, 20-71 nm thickness) and/or ellipsoidal morphologies of HA (273-522 nm width) were observed at 350 °C using HNO3 or CH3COOH to prepare the eggshell and struvite solutions, and NH4OH was used as the pH buffer. The Ca/P (atomic%) ratios obtained ranged between 1.3 and 1.7, indicating the formation of Mg-WH and HA. This study showed that eggshells and struvite usage, along with CH3COOH, are promising resources as potential sustainable precursors and dissolution media, respectively, to produce CaPs with varying morphologies.
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An innovative approach was developed to engineer a multi-layered chitosan scaffold for osteochondral defect repair. A combination of freeze drying and porogen-leaching out methods produced a porous, bioresorbable scaffold with a distinct gradient of pore size (mean = 160-275 µm). Incorporation of 70 wt% nano-hydroxyapatite (nHA) provided additional strength to the bone-like layer. The scaffold showed instantaneous mechanical recovery under compressive loading and did not delaminate under tensile loading. The scaffold supported the attachment and proliferation of human mesenchymal stem cells (MSCs), with typical adherent cell morphology found on the bone layer compared to a rounded cell morphology on the chondrogenic layer. Osteogenic and chondrogenic differentiation of MSCs preferentially occurred in selected layers of the scaffold in vitro, driven by the distinct pore gradient and material composition. This scaffold is a suitable candidate for minimally invasive arthroscopic delivery in the clinic with potential to regenerate damaged cartilage and bone.
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Quitosana , Durapatita , Células-Tronco Mesenquimais/citologia , Nanoestruturas , Alicerces Teciduais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrogênese , Humanos , Células-Tronco Mesenquimais/metabolismo , Microesferas , Osteogênese , Poliésteres , Resistência à TraçãoRESUMO
Titanate structures have been widely investigated as biomedical component surfaces due to their bioactive, osteoinductive and antibacterial properties. However, these surfaces are limited to Ti and its alloys, due to the nature of the chemical conversion employed. The authors present a new method for generating nanoporous titanate structures on alternative biomaterial surfaces, such as other metals/alloys, ceramics and polymers, to produce bioactive and/or antibacterial properties in a simple yet effective way. Wet chemical (NaOH; 5 M; 60 °C; 24 h) conversion of DC magnetron sputtered Ti surfaces on 316L stainless steel were investigated to explore effects of microstructure on sodium titanate conversion. It was found that the more equiaxed thin films (B/300) generated the thickest titanate structures (ca. 1.6 µm), which disagreed with the proposed hypothesis of columnar structures allowing greater NaOH ingress. All film parameters tested ultimately generated titanate structures, as confirmed via EDX, SEM, XPS, XRD, FTIR and Raman analyses. Additionally, the more columnar structures (NB/NH & B/NH) had a greater quantity of Na (ca. 26 at.%) in the top portion of the films, as confirmed via XPS, however, on average the Na content was consistent across the films (ca. 5-9 at.%). Film adhesion for the more columnar structures (ca. 42 MPa), even on polished substrates, were close to that of the FDA requirement for plasma-sprayed HA coatings (ca. 50 MPa). This study demonstrates the potential of these surfaces to be applied onto a wide variety of material types, even polymeric materials, due to the lower processing temperatures utilised, with the vision to generate bioactive and/or antibacterial properties on a plethora of bioinert materials.
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Nanopartículas/química , Óxidos/química , Titânio/química , Teste de Materiais , Tamanho da Partícula , Porosidade , Propriedades de SuperfícieRESUMO
A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of â¼400 µm from three different methacrylated poly(d,l-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.
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Materiais Biomiméticos/farmacologia , Fraturas não Consolidadas/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biomiméticos/química , Caproatos/química , Células Cultivadas , Dioxanos/química , Modelos Animais de Doenças , Feminino , Lactonas/química , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Cultura Primária de Células , Estereolitografia , Engenharia TecidualRESUMO
This study aimed to explore the correlation between mechanical and structural properties of chitosan-agarose blend (Ch-Agrs) scaffolds. Porosity of Ch-Agrs scaffolds was constant at 93%, whilst pore sizes varied between 150 and 550 µm. Pore sizes of the blend scaffolds (150-300 µm) were significantly smaller than for either agarose or chitosan scaffolds alone (ca. 500 µm). Ch50-Agrs50 blend scaffold showed the highest compressive modulus and strength values (4.5 ± 0.4 and 0.35 ± 0.03 MPa) due to reduction in the pore size. The presence of agarose improved the stability of the blends in aqueous media. The increase in compressive properties and residual weight after the TGA test, combined with the reduction in the swelling percentage of the blend scaffolds suggested an interaction between chitosan and agarose via hydrogen bonding which was confirmed using FTIR analysis. All wet blend scaffolds exhibited instant recovery after full compression. This study shows the potential of Ch-Agrs scaffolds for repairing soft tissue.
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Transparent and flexible nanocomposite films with a range of Agarose to Cellulose Nano-Whisker (CNW) ratios were produced using never-dried CNWs. The incorporation of never-dried CNWs within Agarose played an important role in the surface roughness (Ra 7-15â¯nm) and light transparency of the films (from 84 to 90%). Surface induced crystallisation of Agarose by CNWs was also found with increasing percentage of crystallinity (up to 79%) for the nanocomposite films, where CNW acted as nucleating sites. The enhanced tensile strength (ca. 30% increase) and modulus (ca. 90% increase) properties of the nanocomposite films compared to the control Agarose film indicated the effectiveness of the nanowhiskers incorporation. The storage modulus of the nanocomposite films increased also to be tripled Agarose alone as the CNWs content reached 43%. The swelling kinetics of the nanocomposites revealed that addition of CNWs reduced the long-term swelling capacity and swelling rate of the nanocomposite.
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An overview of the formation of calcium phosphate under in vitro environment on the surface of a range of bioactive materials (e.g. from silicate, borate, and phosphate glasses, glass-ceramics, bioceramics to metals) based on recent literature is presented in this review. The mechanism of bone-like calcium phosphate (i.e. hydroxyapatite) formation and the test protocols that are either already in use or currently being investigated for the evaluation of the bioactivity of biomaterials are discussed. This review also highlights the effect of chemical composition and surface charge of materials, types of medium (e.g. simulated body fluid, phosphate-buffered saline and cell culture medium) and test parameters on their bioactivity performance. Finally, a brief summary of the biomedical applications of these newly formed calcium phosphate (either in the form of amorphous or apatite) is presented.
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Fully bioresorbable composites have been investigated in order to replace metal implant plates used for hard tissue repair. Retention of the composite mechanical properties within a physiological environment has been shown to be significantly affected due to loss of the integrity of the fibre/matrix interface. This study investigated phosphate based glass fibre (PGF) reinforced polycaprolactone (PCL) composites with 20%, 35% and 50% fibre volume fractions (Vf) manufactured via an in-situ polymerisation (ISP) process and a conventional laminate stacking (LS) followed by compression moulding. Reinforcing efficiency between the LS and ISP manufacturing process was compared, and the ISP composites revealed significant improvements in mechanical properties when compared to LS composites. The degradation profiles and mechanical properties were monitored in phosphate buffered saline (PBS) at 37°C for 28 days. ISP composites revealed significantly less media uptake and mass loss (p<0.001) throughout the degradation period. The initial flexural properties of ISP composites were substantially higher (p<0.0001) than those of the LS composites, which showed that the ISP manufacturing process provided a significantly enhanced reinforcement effect than the LS process. During the degradation study, statistically higher flexural property retention profiles were also seen for the ISP composites compared to LS composites. SEM micrographs of fracture surfaces for the LS composites revealed dry fibre bundles and poor fibre dispersion with polymer rich zones, which indicated poor interfacial bonding, distribution and adhesion. In contrast, evenly distributed fibres without dry fibre bundles or polymer rich zones, were clearly observed for the ISP composite samples, which showed that a superior fibre/matrix interface was achieved with highly improved adhesion.
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Implantes Absorvíveis , Vidro/química , Fosfatos/química , Poliésteres/química , Teste de MateriaisRESUMO
Tubular scaffolds with aligned polylactic acid (PLA) fibres were fabricated for cell guide applications by immersing rolled PLA fibre mats into a polyvinyl acetate (PVAc) solution to bind the mats. The PVAc solution was also mixed with up to 30 wt % ß-tricalcium phosphate (ß-TCP) content. Cross-sectional images of the scaffold materials obtained via scanning electron microscopy (SEM) revealed the aligned fibre morphology along with a significant number of voids in between the bundles of fibres. The addition of ß-TCP into the scaffolds played an important role in increasing the void content from 17.1% to 25.3% for the 30 wt % ß-TCP loading, which was measured via micro-CT (µCT) analysis. Furthermore, µCT analyses revealed the distribution of aggregated ß-TCP particles in between the various PLA fibre layers of the scaffold. The compressive modulus properties of the scaffolds increased from 66 MPa to 83 MPa and the compressive strength properties decreased from 67 MPa to 41 MPa for the 30 wt % ß-TCP content scaffold. The scaffolds produced were observed to change into a soft and flexible form which demonstrated shape recovery properties after immersion in phosphate buffered saline (PBS) media at 37 °C for 24 h. The cytocompatibility studies (using MG-63 human osteosarcoma cell line) revealed preferential cell proliferation along the longitudinal direction of the fibres as compared to the control tissue culture plastic. The manufacturing process highlighted above reveals a simple process for inducing controlled cell alignment and varying porosity features within tubular scaffolds for potential tissue engineering applications.
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In this study, bioresorbable phosphate-based glass (PBG) fibers were used to reinforce poly(lactic acid) (PLA). PLA/PBG random mat (RM) and unidirectional (UD) composites were prepared via laminate stacking and compression molding with fiber volume fractions between 14% and 18%, respectively. The percentage of water uptake and mass change for UD composites were higher than the RM composites and unreinforced PLA. The crystallinity of the unreinforced PLA and composites increased during the first few weeks and then a plateau was seen. XRD analysis detected a crystalline peak at 16.6° in the unreinforced PLA sample after 42 days of immersion in phosphate buffer solution (PBS) at 37°C. The initial flexural strength of RM and UD composites was â¼106 and â¼115 MPa, whilst the modulus was â¼6.7 and â¼9 GPa, respectively. After 95 days immersion in PBS at 37°C, the strength decreased to 48 and 52 MPa, respectively as a result of fiber-matrix interface degradation. There was no significant change in flexural modulus for the UD composites, whilst the RM composites saw a decrease of â¼45%. The molecular weight of PLA alone, RM, and UD composites decreased linearly with time during degradation due to chain scission of the matrix. Short fiber pull-out was seen from SEM micrographs for both RM and UD composites.