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Three-armed poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-Æ-caprolactone) (P(TMC-co-ε-CL)) macromers with molecular weights of approximately 30 kg mol-1 are synthesized by ring-opening polymerization and subsequent functionalization with methacrylic anhydride. Networks are then prepared by photo-crosslinking. To investigate the in vitro and in vivo degradation properties of these photo-crosslinked networks and assess the effect of ε-caprolactone content on the degradation properties, PTMC networks, and copolymer networks with two different TMC:ε-CL ratios are prepared. PTMC networks degraded slowly, via an enzymatic surface erosion process, both in vitro and in vivo. Networks prepared from P(TMC-co-ε-CL) macromers with a 74:26 ratio are found to degrade slowly as well, via a surface erosion process, albeit at a higher rate compared to PTMC networks. Increasing the ε-CL content to a ratio of 52:48, resulted in a faster degradation. These networks lost their mechanical properties much sooner than the other networks. Thus, PTMC and P(TMC-co-ε-CL) networks are interesting networks for tissue engineering purposes and the exact degradation properties can be tuned by varying the TMC:ε-CL ratio, providing researchers with a tool to obtain copolymer networks with the desired degradation rate depending on the intended application.
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Caproatos , Lactonas , Poliésteres , Polímeros , Polímeros/metabolismo , DioxanosRESUMO
Immunoregulatory polysaccharides from probiotic bacteria have potential in biomedical engineering. Here, a negatively charged exopolysaccharide from Bifidobacterium longum with confirmed immunoregulatory activity (EPS624) was applied in multilayered polyelectrolyte coatings with positively charged chitosan. EPS624 and coatings (1, 5, and 10 layers and alginate-substituted) were characterized by the zeta potential, dynamic light scattering, size exclusion chromatography, scanning electron microscopy, and atomic force microscopy. Peripheral blood mononuclear cells (hPBMCs) and fibroblasts were exposed for 1, 3, 7, and 10 days with cytokine secretion, viability, and morphology as observations. The coatings showed an increased rugosity and exponential growth mode with an increasing number of layers. A dose/layer-dependent IL-10 response was observed in hPBMCs, which was greater than EPS624 in solution and was stable over 7 days. Fibroblast culture revealed no toxicity or metabolic change after exposure to EPS624. The EPS624 polyelectrolyte coatings are cytocompatible, have immunoregulatory properties, and may be suitable for applications in biomedical engineering.
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Bifidobacterium longum , Quitosana , Polieletrólitos , Leucócitos Mononucleares , Polissacarídeos/química , Quitosana/farmacologia , Quitosana/químicaRESUMO
Methacrylated gelatin (GelMA) has been intensively studied as a 3D printable scaffold material in tissue regeneration fields, which can be attributed to its well-known biological functions. However, the long-term stability of photo-crosslinked GelMA scaffolds is hampered by a combination of its fast degradation in the presence of collagenase and the loss of physical crosslinks at higher temperatures. To increase the longer-term shape stability of printed scaffolds, a mixture of GelMA and tyramine-conjugated 8-arm PEG (8PEGTA) was used to create filaments composed of an interpenetrating network (IPN). Photo-crosslinking during filament deposition of the GelMA and subsequent enzymatic crosslinking of the 8PEGTA were applied to the printed 3D scaffolds. Although both crosslinking mechanisms are radical based, they operate without interference of each other. Rheological data of bulk hydrogels showed that the IPN was an elastic hydrogel, having a storage modulus of 6 kPa, independent of temperature in the range of 10 - 40°C. Tensile and compression moduli were 110 kPa and 80 kPa, respectively. On enzymatic degradation in the presence of collagenase, the gelatin content of the IPN fully degraded in 7 days, leaving a stable secondary crosslinked 8PEGTA network. Using a BioMaker bioprinter, hydrogels without and with human osteosarcoma cells (hMG-63) were printed. On culturing for 21 days, hMG-63 in the GelMA/8PEGTA IPN showed a high cell viability (>90%). Thus, the presence of the photoinitiator, incubation with H2O2, and mechanical forces during printing did not hamper cell viability. This study shows that the GelMA/8PEGTA ink is a good candidate to generate cell-laden bioinks for extrusion-based printing of constructs for tissue engineering applications.
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To improve the mechanical performance of hyaluronic acid (HA)-based hydrogels, we prepared novel hybrid hydrogels consisting of hydrophilic HA and hydrophobic poly(trimethylene carbonate) (PTMC). Both polymers were functionalized with methacrylic anhydride, yielding HAMA and PTMC-tMA. Hybrid networks with different ratios of PTMC-tMA:HAMA were prepared by photo-cross-linking, using DMSO pH 2.7 as a common solvent for both macromers. The hybrid networks had high gel contents. The hydrophilicity of the networks increased with increasing HAMA content. The networks consisted of the intended amounts of both macromers. The suture retention strength and compression modulus of the networks increased with increasing PTMC-tMA content. While the 100% HAMA network could not be sutured, the 50:50 PTMC-tMA:HAMA network had a suture retention strength of 5.3 N/mm. This is comparable to that of natural vascular tissues. Also the compression modulus (867 kPa) was significantly higher than that of the 100% HAMA network (13 kPa). Moreover, the networks were compatible with human mesenchymal stem cells. In conclusion, these resilient PTMC-tMA:HAMA networks are promising new biomaterials for tissue regeneration.
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Applying biodegradable osteosyntheses avoids the disadvantages of titanium osteosyntheses. However, foreign-body reactions remain a major concern and evidence of complete resorption is lacking. This study compared the physico-chemical properties, histological response and radiographs of four copolymeric biodegradable osteosynthesis systems in a goat model with 48-months follow-up. The systems were implanted subperiosteally in both tibia and radius of 12 Dutch White goats. The BioSorb FX [poly(70LLA-co-30DLLA)], Inion CPS [poly([70-78.5]LLA-co-[16-24]DLLA-co-4TMC)], SonicWeld Rx [poly(DLLA)], LactoSorb [poly(82LLA-co-18GA)] systems and a negative control were randomly implanted in each extremity. Samples were assessed at 6-, 12-, 18-, 24-, 36-, and 48-month follow-up. Surface topography was performed using scanning electron microscopy (SEM). Differential scanning calorimetry and gel permeation chromatography were performed on initial and explanted samples. Histological sections were systematically assessed by two blinded researchers using (polarized) light microscopy, SEM and energy-dispersive X-ray analysis. The SonicWeld Rx system was amorphous while the others were semi-crystalline. Foreign-body reactions were not observed during the complete follow-up. The SonicWeld Rx and LactoSorb systems reached bone percentages of negative controls after 18 months while the BioSorb Fx and Inion CPS systems reached these levels after 36 months. The SonicWeld Rx system showed the most predictable degradation profile. All the biodegradable systems were safe to use and well-tolerated (i.e., complete implant replacement by bone, no clinical or histological foreign body reactions, no [sterile] abscess formation, no re-interventions needed), but nanoscale residual polymeric fragments were observed at every system's assessment.
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A new generation of sophisticated tissue engineering scaffolds are developed using the periodicity of trigonometric equations to generate triply periodic minimal surfaces (TPMS). TPMS architectures display minimal surface energy that induce typical pore features and surface curvatures. Here we described a series of TPMS geometries and developed a procedure to build such scaffolds by stereolithography using biocompatible and biodegradable photosensitive resins.
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Estereolitografia , Engenharia Tecidual/instrumentação , Alicerces Teciduais/química , Implantes Absorvíveis , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Osso e Ossos/fisiologia , Desenho Assistido por Computador , Reagentes de Ligações Cruzadas/química , Humanos , Poliésteres/síntese química , Poliésteres/química , Porosidade , Propriedades de Superfície , Engenharia Tecidual/métodosRESUMO
As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or pre-clinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.
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Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that Staphylococcus aureus can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections.
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OBJECTIVE: Bone infections are challenging to treat because of limited capability of systemic antibiotics to accumulate at the bone site. To enhance therapeutic action, systemic treatments are commonly combined with local antibiotic-loaded materials. Nevertheless, available drug carriers have undesirable properties, including inappropriate antibiotic release profiles and nonbiodegradability. To alleviate such limitations, we aim to develop a drug delivery system (DDS) for local administration that can interact strongly with bone mineral, releasing antibiotics at the infected bone site. METHODS: Biodegradable polyesters (poly (ε-caprolactone) or poly (D,l-lactic acid)) were selected to fabricate antibiotic-loaded microspheres by oil in water emulsion. Antibiotic release and antimicrobial effects on Staphylococcus aureus were assessed by zone of inhibition measurements. Microsphere bone affinity was increased by functionalising the bisphosphonate drug alendronate to the microsphere surface using carbodiimide chemistry. Effect of bone targeting microspheres on bone homeostasis was tested by looking at the resorption potential of osteoclasts exposed to the developed microspheres. RESULTS: In vitro, the antibiotic release profile from the microspheres was shown to be dependent on the polymer used and the microsphere preparation method. Mineral binding assays revealed that microsphere surface modification with alendronate significantly enhanced interaction with bone-like materials. Additionally, alendronate functionalised microspheres did not differentially affect osteoclast mineral resorption in vitro, compared with nonfunctionalised microspheres. CONCLUSION: We report the development and characterisation of a DDS which can release antibiotics in a sustained manner. Surface-grafted alendronate groups enhanced bone affinity of the microsphere construct, resulting in a bone targeting DDS. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The DDS presented can be loaded with hydrophobic antibiotics, representing a potential, versatile and biodegradable candidate to locally treat bone infection.
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Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long-term large animal models. An ovine AF injury model was developed using cervical spinal levels and a biopsy-type AF defect to assess composite tissue engineering repair in 1-month and 12-month studies. The repair used a fibrin hydrogel crosslinked with genipin (FibGen) to seal defects, poly(trimethylene carbonate) (PTMC) scaffolds to replace lost AF tissue, and polyurethane membranes to prevent herniation. In the 1-month study, PTMC scaffolds sealed with FibGen herniated with polyurethane membranes. When applied alone, FibGen integrated with the surrounding AF tissue without herniation, showing promise for long-term studies. The 12-month long-term study used only FibGen which showed fibrous healing, biomaterial resorption and no obvious hydrogel-related complications. However, the 2 mm biopsy punch injury condition also exhibited fibrotic healing at 12 months. Both untreated and FibGen treated groups showed equivalency with no detectable differences in histological grades of proteoglycans, cellular morphology, IVD structure and blood vessel formation, biomechanical properties including torque range and axial range of motion, Pfirrmann grade, IVD height, and quantitative scores of vertebral body changes from clinical computed tomography. The biopsy-type injury caused endplate defects with a high prevalence of osteophytes in all groups and no nucleus herniation, indicating that the biopsy-type injury requires further refinement, such as reduction to a slit-type defect that could penetrate the full depth of the AF without damaging the endplate. Results demonstrate translational feasibility of FibGen for AF repair to seal AF defects, although future study with a more refined injury model is required to validate the efficacy of FibGen before translation.
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The orbital floor (OF) is an anatomical location in the craniomaxillofacial (CMF) region known to be highly variable in shape and size. When fractured, implants commonly consisting of titanium meshes are customized by plying and crude hand-shaping. Nevertheless, more precise customized synthetic grafts are needed to meticulously reconstruct the patients' OF anatomy with better fidelity. As alternative to titanium mesh implants dedicated to OF repair, we propose a flexible patient-specific implant (PSI) made by stereolithography (SLA), offering a high degree of control over its geometry and architecture. The PSI is made of biodegradable poly(trimethylene carbonate) (PTMC) loaded with 40 wt % of hydroxyapatite (called Osteo-PTMC). In this work, we developed a complete work-flow for the additive manufacturing of PSIs to be used to repair the fractured OF, which is clinically relevant for individualized medicine. This work-flow consists of (i) the surgical planning, (ii) the design of virtual PSIs and (iii) their fabrication by SLA, (iv) the monitoring and (v) the biological evaluation in a preclinical large-animal model. We have found that once implanted, titanium meshes resulted in fibrous tissue encapsulation, whereas Osteo-PMTC resulted in rapid neovascularization and bone morphogenesis, both ectopically and in the OF region, and without the need of additional biotherapeutics such as bone morphogenic proteins. Our study supports the hypothesis that the composite osteoinductive Osteo-PTMC brings advantages compared to standard titanium mesh, by stimulating bone neoformation in the OF defects. PSIs made of Osteo-PTMC represent a significant advancement for patients whereby the anatomical characteristics of the OF defect restrict the utilization of traditional hand-shaped titanium mesh.
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Procedimentos de Cirurgia Plástica , Estereolitografia , Animais , Durapatita , Humanos , Órbita , Próteses e Implantes , Telas Cirúrgicas , TitânioRESUMO
For the study of polymer networks, having access to polymer networks with a controlled and well-defined microscopic network structure is of great importance. However, typically, such networks are difficult to synthesize. In this work, a simple, effective, and widely applicable method is presented for synthesizing polymer networks with a well-defined network structure. This is done by the functionalization of polymeric diols using a diisocyanate, and their subsequent trimerization. Using hexamethylene diisocyanate and hydroxyl-group-terminated poly(ε-caprolactone) and poly(ethylene glycol), it is shown that both hydrophobic and hydrophilic poly(urethane-isocyanurate) networks with a well-defined network structure can readily be synthesized. By using in situ infrared spectroscopy, it is shown that the trimerization of isocyanate endgroups is clearly the predominant reaction pathway of network formation, supporting the proposed mechanism and network structure. The resulting networks possess excellent mechanical properties in both the dry and in the wet state.
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Materiais Biocompatíveis/química , Isocianatos/química , Polímeros/química , Teste de Materiais , Polietilenoglicóis/química , Poliuretanos/químicaRESUMO
One of the key challenges for neural tissue engineering is to exploit functional materials to guide and support nerve regeneration. Currently, reduced graphene oxide (rGO), which is well-known for its unique electrical and mechanical properties, has been incorporated into biocompatible polymers to manufacture functional scaffolds for nerve tissue engineering. However, rGO has poor dispersity in polymer matrix, which limits its further application. Here, we replaced rGO with rGO-graft-PTMC. The rGO-graft-PTMC was firstly prepared by grafting trimethylene carbonate (TMC) oligomers onto rGO. Subsequently, PTMC/rGO-graft-PTMC composite fibrous mats were fabricated by electrospinning of a dispersion of PTMC and rGO-graft-PTMC. The loading of rGO-graft-PTMC could reach up to 6 wt% relative to PTMC. Scanning electron microscopy images showed that the morphologies and average diameters of PTMC/rGO-graft-PTMC composite fibrous mats were affected by the content of rGO-graft-PTMC. Additionally, the incorporation of rGO-graft-PTMC resulted in enhanced thermal stability and hydrophobicity of PTMC fibers. Biological results demonstrated that PC12 cells showed higher cell viability on PTMC/rGO-graft-PTMC fibers of 2.4, 4.0 and 6.0 wt% rGO-graft-PTMC compared to pure PTMC fibers. These results suggest that PTMC/rGO-graft-PTMC composite fibrous structures hold great potential for neural tissue engineering.
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Dioxanos/química , Grafite/química , Regeneração Nervosa , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Adesão Celular , Sobrevivência Celular , Eletroquímica , Teste de Materiais/métodos , Óxidos/química , Células PC12 , Polímeros/química , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , TermogravimetriaRESUMO
Stereolithography-assisted fabrication of hydrogels of carboxybetaine methacrylamide (CBMAA) and a α,ω-methacrylate poly(d,l-lactide-block-ethylene glycol-block- d,l-lactide) (MA-PDLLA-PEG-PDLLA-MA) telechelic triblock macromer is presented. This technique allows printing complex structures with gyroid interconnected porosity possessing extremely high specific area. Hydrogels are characterized by infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and laser scanning confocal microscopy (LSCM). The copolymerization with zwitterionic comonomer leads hydrogels with high equilibrium water content (EWC), up to 700% while maintaining mechanical robustness. The introduction of carboxybetaine yields excellent resistance to nonspecific protein adsorption while providing a facile way for specific biofunctionalization with a model protein, fluorescein isothiocyanate labeled bovine serum albumin (BSA). The homogeneous protein immobilization across the hydrogel pores prove the accessibility to the innermost pore volumes. The remarkably low protein adsorption combined with the interconnected nature of the porosity allowing fast diffusion of nutrient and waste product and the mimicry of bone trabecular, makes the hydrogels presented here highly attractive for tissue engineering.
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Hidrogéis/química , Metacrilatos/química , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Bovinos , PorosidadeRESUMO
Biomaterial-associated infection (BAI) is a major cause of the failure of biomaterials/medical devices. Staphylococcus aureus is one of the major pathogens in BAI. Current experimental BAI mammalian animal models such as mouse models are costly and time-consuming, and therefore not suitable for high throughput analysis. Thus, novel animal models as complementary systems for investigating BAI in vivo are desired. In the present study, we aimed to develop a zebrafish embryo model for in vivo visualization and intravital analysis of bacterial infection in the presence of biomaterials based on fluorescence microscopy. In addition, the provoked macrophage response was studied. To this end, we used fluorescent protein-expressing S. aureus and transgenic zebrafish embryos expressing fluorescent proteins in their macrophages and developed a procedure to inject bacteria alone or together with microspheres into the muscle tissue of embryos. To monitor bacterial infection progression in live embryos over time, we devised a simple but reliable method of microscopic scoring of fluorescent bacteria. The results from microscopic scoring showed that all embryos with more than 20 colony-forming units (CFU) of bacteria yielded a positive fluorescent signal of bacteria. To study the potential effects of biomaterials on infection, we determined the CFU numbers of S. aureus with and without 10 µm polystyrene microspheres (PS10) as model biomaterials in the embryos. Moreover, we used the ObjectJ project file "Zebrafish-Immunotest" operating in ImageJ to quantify the fluorescence intensity of S. aureus infection with and without PS10 over time. Results from both methods showed higher numbers of S. aureus in infected embryos with microspheres than in embryos without microspheres, indicating an increased infection susceptibility in the presence of the biomaterial. Thus, the present study shows the potential of the zebrafish embryo model to study BAI with the methods developed here.
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Infecções Estafilocócicas , Staphylococcus aureus , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados , Materiais Biocompatíveis , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Fluorescência , Macrófagos , Microesferas , Poliestirenos , Peixe-Zebra/microbiologiaRESUMO
Graphene-graft-polymer has been used to improve the compatibility between graphene and a polymer matrix, and to further enhance electrical, mechanical and biological properties of polymer/graphene composites. In this study, poly(trimethylene carbonate) (PTMC) was successfully grafted onto graphene surface via 'grafting from' method. Reduced graphene oxide (rGO) initiator was synthesized by azido ethanol reaction with graphene oxide (GO) at high temperature. This resulted in thermal reduction of the GO and stable hydroxyl groups on the graphene surface. Subsequently, rGO initiator was used for the ring-opening polymerization of TMC monomer. rGO-graft-PTMC composites with PTMC molecular weights of 430, 480, 2150 and 7030 g mol-1 were successfully synthesized using different amounts of TMC. Single layer graphene nanosheets remained after graft polymerization by this method. rGO-graft-PTMC dispersions in chloroform were stable. The rGO-graft-PTMC composites with PTMC molecular weights of 430-7030 g mol-1 had electrical conductivities ranging from 0.2 to 0.016 s cm-1. To investigate the biocompatibility of rGO-graft-PTMC, PTMC-based films containing rGO-graft-PTMC were prepared and used in cell culturing experiments. The composite films showed good biocompatibility with PC12 neuronal cells. It is concluded that rGO-graft-PTMC composite is a promising material for the preparation of nerve regeneration conduits.
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Materiais Biocompatíveis/química , Dioxanos/química , Regeneração Nervosa , Polímeros/química , Alicerces Teciduais , Animais , Condutividade Elétrica , Eletricidade , Grafite , Teste de Materiais , Peso Molecular , Neurônios/fisiologia , Células PC12 , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Engenharia Tecidual/métodosRESUMO
Bone defect repair is a challenging clinical problem in musculoskeletal system, especially in orthopaedic disorders such as steroid associated osteonecrosis (SAON). Magnesium (Mg) as a biodegradable metal with properly mechanical properties has been investigating for a long history. In this study, Mg powder, poly (lactide-co-glycolide) (PLGA), ß-tricalcium phosphate (ß-TCP) were the elements to formulate a novel porous PLGA/TCP/Mg (PTM) scaffolds using low temperature rapid prototyping (LT-RP) technology. The physical characterization of PTM scaffold and Mg ions release were analyzed in vitro. The osteogenic and angiogenic properties of PTM scaffolds, as well as the biosafety after implantation were assessed in an established SAON rabbit model. Our results showed that the PTM scaffold possessed well-designed bio-mimic structure and improved mechanical properties. Findings of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and micro-computed tomography (micro CT)-based angiography indicated that PTM scaffold could increase blood perfusion and promote new vessel ingrowth at 4 weeks after surgery, meanwhile, a plenty of newly formed vessels with well-architective structure were observed at 8 weeks. Correspondingly, at 12 weeks after surgery, micro-CT, histological and mechanical properties analysis showed that PTM could significant enhance new bone formation and strengthen newly formed bone mechanical properties. The mean bone volume in PTM group was 56.3% greater than that in PT group. Biosafety assessments from 0 to 12 weeks after implantation did not induce increase in serum Mg ions concentration, and immune response, liver and kidney function parameters were all at normal level. These findings suggested that the PTM scaffold had both osteogenic and angiogenic abilities which were synergistic effect in enhancing new bone formation and strengthen newly formed bone quality in SAON. In summary, PTM scaffolds are promising composite biomaterials for repairing challenging bone defect that would have great potential for its clinical translation.
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Fosfatos de Cálcio/química , Magnésio/química , Osteogênese , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Fêmur/irrigação sanguínea , Fêmur/lesões , Fêmur/fisiologia , Magnésio/uso terapêutico , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/uso terapêutico , Porosidade , Impressão Tridimensional , CoelhosRESUMO
Photo-crosslinked synthetic biodegradable polymer networks are highly interesting materials for utilization in biomedical applications such as drug delivery, cell encapsulation and tissue engineering scaffolds. Varying the architecture, chemistry, degree of functionalization and molecular weight of the macromer precursor molecules results in networks with a wide range of physical- and mechanical properties, crosslinking densities, degradation characteristics and thus in potential applications. Photo-crosslinked networks can easily be prepared and have the possibility to entrap a wide range of (biologically active) substances and cells. Additionally, spatial and temporal control over the crosslinking process when using additive manufacturing processes, allows for the preparation of network structures with complex shapes. Photo-crosslinked networks have been used to prepare drug delivery devices, as these networks allow for drug delivery in a controlled way over a prolonged period of time. Furthermore, additive manufacturing techniques such as extrusion-based additive manufacturing and stereolithography have been used to prepare photo-crosslinked tissue engineering scaffolds. This allows for the preparation of designed porous structures with precise control over the pore size and pore architecture and optimal mechanical properties. In particular for stereolithography, a wide variety of resins based on biodegradable photo-crosslinkable macromers has been developed.
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Materiais Biocompatíveis/síntese química , Plásticos Biodegradáveis/síntese química , Reagentes de Ligações Cruzadas/química , Processos Fotoquímicos , Animais , Linhagem Celular , Portadores de Fármacos/química , Humanos , Fenômenos Mecânicos , Polimerização , Porosidade , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(É-caprolactone)-b-poly(ethylene glycol)-b-poly(É-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30 and 70 mol%. These showed excellent mechanical properties not only when dry, but also when hydrated: TPUs prepared from PCL-b-PEG-b-PCL with PEG of Mn 6 kg/mol (PCL7-PEG6-PCL7) took up 122 wt.% upon hydration and had an E-modulus of 52 ± 10 MPa, a tensile strength of 17 ± 2 MPa, and a strain at break of 1553 ± 155% in the hydrated state. They had a fracture energy of 17976 ± 3011 N/mm² and a high tearing energy of 72 kJ/m². TPUs prepared using PEG with Mn of 10 kg/mol (PCL5-PEG10-PCL5) took up 534% water and were more flexible. When wet, they had an E-modulus of 7 ± 2 MPa, a tensile strength of 4 ± 1 MPa, and a strain at break of 147 ± 41%. These hydrogels had a fracture energy of 513 ± 267 N/mm² and a tearing energy of 16 kJ/m². The latter TPU was first extruded into filaments and then processed into designed porous hydrogel structures by 3D-printing. These hydrogels can be used in 3D printing of tissue engineering scaffolds with high fracture toughness.
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BACKGROUND: Poly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photo-fabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes. METHODS: In this context, we propose here, as a proof of concept, to load a drug model (dexamethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films' properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays. RESULTS: The polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation. CONCLUSION: This study demonstrates the potential of polymer-polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.