114 research outputs found

    A critical review on polydopamine surface-modified scaffolds in musculoskeletal regeneration

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    Increasing concern about age-related diseases, particularly musculoskeletal injuries and orthopedic conditions, highlights the need for strategies such as tissue engineering to address them. Surface modification has been developed to create pro-healing interfaces, personalize scaffolds and provide novel medicines. Polydopamine, a mussel-inspired adhesive polymer with highly reactive functional groups that adhere to nearly all substrates, has gained attention in surface modification strategies for biomaterials. Polydopamine was primarily developed to modify surfaces, but its effectiveness has opened up promising approaches for further applications in bioengineering as carriers and nanoparticles. This review focuses on the recent discoveries of the role of polydopamine as a surface coating material, with focus on the properties that make it suitable for tackling musculoskeletal disorders. We report the evolution of using it in research, and discuss papers involving the progress of this field. The current research on the role of polydopamine in bone, cartilage, muscle, nerve, and tendon regeneration is discussed, thus giving comprehensive overview about the function of polydopamine both in-vitro and in-vivo. Finally, the report concludes presenting the critical challenges that must be addressed for the clinical translation of this biomaterial while exploring future perspectives and research opportunities in this area

    Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

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    Osteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients’ quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds - from monophasic to multiphasic constructs - is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements

    Eularian wall film model for predicting dynamic cell culture process to evaluate scaffold design in a perfusion bioreactor

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    In tissue engineering field, it is important to develop a suitable numerical model to evaluate scaffold geometry design. The experimental evaluation of the effect of each specific scaffold parameter on tissue regeneration requires large cost and long time expend. Dynamic cell culture is commonly used for generating tissues which could replace damaged tissues. A perfusion bioreactor model is developed which is able to simulate dynamic cell culture, to evaluate scaffold quality. The wall-film model is used to simulate cell attachment with the assumption that cells could be seen as liquid drops. In the process of cell attachment, the cells could impinge to a solid surface and form a liquid film which were considered as cell attached on the scaffold surface. Two types of cell-scaffold interactions were involved in numerical models including trap model and Stanton-Rutland (Cell impinge model—CIM) model. For trap model, all cells impinged the scaffold are seen as attached. For Stanton-Rutland model, four regimes of cell-scaffold interaction are involved in the cell attachment, including stick, rebound, spread, and splash, and only stick and spread are seen as attached. By comparison with two different numerical methods, the results showed that CIM model result is more related to the experimental results than trap model, which indicated that four regimes of cell-scaffold interaction occurred in cell attachment process. By evaluating two different geometry scaffold's cells seeding by these two models, the results further indicated that this model are able to use for assessing the scaffold design

    Determination of an Initial Stage of the Bone Tissue Ingrowth Into Titanium Matrix by Cell Adhesion Model

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    For achieving early intervention treatment to help patients delay or avoid joint replacement surgery, a personalized scaffold should be designed coupling the effects of mechanical, fluid mechanical, chemical, and biological factors on tissue regeneration, which results in time- and cost-consuming trial-and-error analyses to investigate the in vivo test and related experimental tests. To optimize the fluid mechanical and material properties to predict osteogenesis and cartilage regeneration for the in vivo and clinical trial, a simulation approach is developed for scaffold design, which is composed of a volume of a fluid model for simulating the bone marrow filling process of the bone marrow and air, as well as a discrete phase model and a cell impingement model for tracking cell movement during bone marrow fillings. The bone marrow is treated as a non-Newtonian fluid, rather than a Newtonian fluid, because of its viscoelastic property. The simulation results indicated that the biofunctional bionic scaffold with a dense layer to prevent the bone marrow flow to the cartilage layer and synovia to flow into the trabecular bone area guarantee good osteogenesis and cartilage regeneration, which leads to high-accuracy in vivo tests in sheep . This approach not only predicts the final bioperformance of the scaffold but also could optimize the scaffold structure and materials by their biochemical, biological, and biomechanical properties

    On the use of continuous spectrum and discrete-mode differential models to predict contraction-flow pressure drops for Boger fluids

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    Over recent years, there has been slow but steady progress towards the qualitative numerical prediction of observed behaviour when highly elastic Boger fluids flow in contraction geometries. This has led to an obvious desire to seek quantitative agreement between prediction and experiment, a subject which is addressed in the current paper. We conclude that constitutive models of non-trivial complexity are required to make headway in this regard. However, we suggest that the desire to move from qualitative to quantitative agreement between theory and experiment is making real progress. In the present case with differential models, this has involved the introduction of a generalized continuous spectrum model. This is based on direct data input from material functions and rheometrical measurements. The class of such models assumes functional separability across shear and extensional deformation, through two master functions, governing independently material-time and viscous-response. The consequences of such a continuous spectrum representation are compared and contrasted against discrete-mode alternatives, via an averaged single-mode approximation and a multi-modal approximation. The effectiveness of each chosen form is gauged by the quality of match to complex flow response and experimental measurement. Here, this is interpreted in circular contraction-type flows with Boger fluids, where large experimental pressure-drop data are available and wide disparity between different fluid responses has been recorded in the past. Findings are then back-correlated to base-material response from ideal viscometric flow

    On the morphological deviation in additive manufacturing of porous Ti6Al4V scaffold: a design consideration

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    Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (-3.0% excess) for vertical struts to 92.8 μm (-8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (-3.0% excess) to 168.7 μm (-21.1% excess). Compressive Young's modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young's modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds

    Bilayered scaffold with 3D printed stiff subchondral bony compartment to provide constant mechanical support for long-term cartilage regeneration

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    BACKGROUND/OBJECTIVE: We seek to figure out the effect of stable and powerful mechanical microenvironment provided by Ti alloy as a part of subchondral bone scaffold on long-term cartilage regeneration. METHODS: we developed a bilayered osteochondral scaffold based on the assumption that a stiff subchondral bony compartment would provide stable mechanical support for cartilage regeneration and enhance subchondral bone regeneration. The subchondral bony compartment was prepared from 3D printed Ti alloy, and the cartilage compartment was created from a freeze-dried collagen sponge, which was reinforced by poly-lactic-co-glycolic acid (PLGA). RESULTS: In vitro evaluations confirmed the biocompatibility of the scaffold materials, while in vivo evaluations demonstrated that the mechanical support provided by 3D printed Ti alloy layer plays an important role in the long-term regeneration of cartilage by accelerating osteochondral formation and its integration with the adjacent host tissue in osteochondral defect model at rabbit femoral trochlea after 24 weeks. CONCLUSION: Mechanical support provided by 3D printing Ti alloy promotes cartilage regeneration by promoting subchondral bone regeneration and providing mechanical support platform for cartilage synergistically. TRANSITIONAL POTENTIAL STATEMENT: The raw materials used in our double-layer osteochondral scaffolds are all FDA approved materials for clinical use. 3D printed titanium alloy scaffolds can promote bone regeneration and provide mechanical support for cartilage regeneration, which is very suitable for clinical scenes of osteochondral defects. In fact, we are conducting clinical trials based on our scaffolds. We believe that in the near future, the scaffold we designed and developed can be formally applied in clinical practice

    miR-455-5p downregulation promotes inflammation pathways in the relapse phase of relapsing-remitting multiple sclerosis disease

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    MicroRNA-455-5p (miR-455-5p) seems to have an anti-inflammatory role in the immune system since its expression is induced by IL-10 cytokine. Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the central nervous system that is caused by an autoimmune inflammatory attack against the myelin insulation of neurons. The expression level of miR-455-5p and its role in MS pathogenesis has yet to be elucidated. We found that miR-455-5p expression was highly correlated with disease severity in MS patients. miR-455-5p expression inversely correlates with its inflammatory-predicted targets (MyD88 and REL) in relapse- and remitting-phase patients. Luciferase assays confirm that MyD88 and REL are direct targets of miR-455-5p. This study represents the first report of the miR-455-5p acts as an anti-inflammatory role in MS, at least partially through targeting MyD88 and REL. This study may provide important information for the use of miR-455-5p as a novel strategy to improve the severity of disease and control inflammation and attack in MS patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

    Transverse propagation of action potentials between parallel chains of cardiac muscle and smooth muscle cells in PSpice simulations

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    BACKGROUND: We previously examined transverse propagation of action potentials between 2 and 3 parallel chain of cardiac muscle cells (CMC) simulated using the PSpice program. The present study was done to examine transverse propagation between 5 parallel chains in an expanded model of CMC and smooth muscle cells (SMC). METHODS: Excitation was transmitted from cell to cell along a strand of 5 cells not connected by low-resistance tunnels (gap-junction connexons). The entire surface membrane of each cell fired nearly simultaneously, and nearly all the propagation time was spent at the cell junctions, the junctional delay time being about 0.3 – 0.5 ms (CMC) or 0.8 – 1.6 ms (SMC). A negative cleft potential (V(jc)) develops in the narrow junctional clefts, whose magnitude depends on the radial cleft resistance (R(jc)), which depolarizes the postjunctional membrane (post-JM) to threshold. Propagation velocity (θ) increased with amplitude of V(jc). Therefore, one mechanism for the transfer of excitation from one cell to the next is by the electric field (EF) that is generated in the junctional cleft when the pre-JM fires. In the present study, 5 parallel stands of 5 cells each (5 × 5 model) were used. RESULTS: With electrical stimulation of the first cell of the first strand (cell A1), propagation rapidly spread down that chain and then jumped to the second strand (B chain), followed by jumping to the third, fourth, and fifth strands (C, D, E chains). The rapidity by which the parallel chains became activated depended on the longitudinal resistance of the narrow extracellular cleft between the parallel strands (R(ol2)); the higher the R(ol2 )resistance, the faster the θ. The transverse resistance of the cleft (R(or2)) had almost no effect. Increasing R(jc )decreases the total propagation time (TPT) over the 25-cell network. When the first cell of the third strand (cell C1) was stimulated, propagation spread down the C chain and jumped to the other two strands (B and D) nearly simultaneously. CONCLUSIONS: Transverse propagation of excitation occurred at multiple points along the chain as longitudinal propagation was occurring, causing the APs in the contiguous chains to become bunched up. Transverse propagation was more erratic and labile in SMC compared to CMC. Transverse transmission of excitation did not require low-resistance connections between the chains, but instead depended on the value of R(ol2). The tighter the packing of the chains facilitated transverse propagation
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