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Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration.

ABSTRACT: Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

SUBMITTER: Chen P

PROVIDER: S-EPMC6525998 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Desktop-Stereolithography 3D Printing of a Polyporous Extracellular Matrix Bioink for Bone Defect Regeneration.

Project description:IntroductionDecellularized tendon extracellular matrix (tECM) perfectly provides the natural environment and holds great potential for bone regeneration in Bone tissue engineering (BTE) area. However, its densifying fiber structure leads to reduced cell permeability. Our study aimed to combine tECM with polyethylene glycol diacrylate (PEGDA) to form a biological scaffold with appropriate porosity and strength using stereolithography (SLA) technology for bone defect repair.MethodsThe tECM was produced and evaluated. Mesenchymal stem cell (MSC) was used to evaluate the biocompatibility of PEGDA/tECM bioink in vitro. Mineralization ability of the bioink was also evaluated in vitro. After preparing 3D printed polyporous PEGDA/tECM scaffolds (3D-pPES) via SLA, the calvarial defect generation capacity of 3D-pPES was assessed.ResultsThe tECM was obtained and the decellularized effect was confirmed. The tECM increased the swelling ratio and porosity of PEGDA bioink, both cellular proliferation and biomineralization in vitro of the bioink were significantly optimized. The 3D-pPES was fabricated. Compared to the control group, increased cell migration efficiency, up-regulation of osteogenic differentiation RNA level, and better calvarial defect repair in rat of the 3D-pPES group were observed.ConclusionThis study demonstrates that the 3D-pPES may be a promising strategy for bone defect treatment.

| S-EPMC7677189 | biostudies-literature

Desktop-Stereolithography 3D-Printing of a Poly(dimethylsiloxane)-Based Material with Sylgard-184 Properties.

Project description:The advantageous physiochemical properties of poly(dimethylsiloxane) (PDMS) have made it an extremely useful material for prototyping in various technological, scientific, and clinical areas. However, PDMS molding is a manual procedure and requires tedious assembly steps, especially for 3D designs, thereby limiting its access and usability. On the other hand, automated digital manufacturing processes such as stereolithography (SL) enable true 3D design and fabrication. Here the formulation, characterization, and SL application of a 3D-printable PDMS resin (3DP-PDMS) based on commercially available PDMS-methacrylate macromers, a high-efficiency photoinitiator and a high-absorbance photosensitizer, is reported. Using a desktop SL-printer, optically transparent submillimeter structures and microfluidic channels are demonstrated. An optimized blend of PDMS-methacrylate macromers is also used to SL-print structures with mechanical properties similar to conventional thermally cured PDMS (Sylgard-184). Furthermore, it is shown that SL-printed 3DP-PDMS substrates can be rendered suitable for mammalian cell culture. The 3DP-PDMS resin enables assembly-free, automated, digital manufacturing of PDMS, which should facilitate the prototyping of devices for microfluidics, organ-on-chip platforms, soft robotics, flexible electronics, and sensors, among others.

| S-EPMC6286193 | biostudies-literature

Silk Fibroin Bioink for 3D Printing in Tissue Regeneration: Controlled Release of MSC extracellular Vesicles.

Project description:Sodium alginate (SA)-based hydrogels are often employed as bioink for three-dimensional (3D) scaffold bioprinting. They offer a suitable environment for cell proliferation and differentiation during tissue regeneration and also control the release of growth factors and mesenchymal stem cell secretome, which is useful for scaffold biointegration. However, such hydrogels show poor mechanical properties, fast-release kinetics, and low biological performance, hampering their successful clinical application. In this work, silk fibroin (SF), a protein with excellent biomechanical properties frequently used for controlled drug release, was blended with SA to obtain improved bioink and scaffold properties. Firstly, we produced a printable SA solution containing SF capable of the conformational change from Silk I (random coil) to Silk II (β-sheet): this transition is a fundamental condition to improve the scaffold's mechanical properties. Then, the SA-SF blends' printability and shape fidelity were demonstrated, and mechanical characterization of the printed hydrogels was performed: SF significantly increased compressive elastic modulus, while no influence on tensile response was detected. Finally, the release profile of Lyosecretome-a freeze-dried formulation of MSC-secretome containing extracellular vesicles (EV)-from scaffolds was determined: SF not only dramatically slowed the EV release rate, but also modified the kinetics and mechanism release with respect to the baseline of SA hydrogel. Overall, these results lay the foundation for the development of SA-SF bioinks with modulable mechanical and EV-release properties, and their application in 3D scaffold printing.

| S-EPMC9959026 | biostudies-literature

Osteochondral Autograft Transfer Technique for Glenoid Osteochondral Defect.

Project description:Glenoid osteochondral defects can be a significant source of pain and disability in an active population. Many treatments are available, but most joint-preserving procedures are limited to debridement, abrasion chondroplasty, or marrow-stimulation techniques, all of which depend on healthy underlying bone and none of which address underlying bony pathology. Osteochondral autograft transfer has been a successful form of treatment for lesions in the knee, elbow, and ankle, especially when subchondral bone is involved. We describe an arthroscopic method of treating glenoid osteochondral lesions with an osteochondral autograft transfer using a graft from the patient's ipsilateral knee. This technique addresses both cartilage and osseous pathology with minimal morbidity and provides a good biological restorative option for patients with isolated glenoid osteochondral defects.

| S-EPMC5123990 | biostudies-literature

The Influence of Printing Parameters and Cell Density on Bioink Printing Outcomes.

Project description:Bioink printability persists as a limiting factor toward many bioprinting applications. Printing parameter selection is largely user-dependent, and the effect of cell density on printability has not been thoroughly investigated. Recently, methods have been developed to give greater insight into printing outcomes. This study aims to further advance those methods and apply them to study the effect of printing parameters (feedrate and flowrate) and cell density on printability. Two printed structures, a crosshatch and five-layer tube, were established as printing standards and utilized to determine the printing outcomes. Acellular bioinks were printed using a testing matrix of feedrates of 37.5, 75, 150, 300, and 600 mm/min and flowrates of 21, 42, 84, 168, and 336 mm3/min. Structures were also printed with cell densities of 5, 10, 20, and 40 × 106 cell/mL at 150 mm/min and 84 mm3/min. Only speed ratios (defined as flowrate divided by feedrate) from 0.07 to 2.24 mm2 were suitable for analysis. Increasing speed ratio dramatically increased the height, width, and wall thickness of tubular structures, but did not influence radial accuracy. For crosshatch structures, the area of pores and the frequency of broken filaments were decreased without impacting pore shape (Pr). Within speed ratios, feedrate and flowrate had negligible, inconsistent effects. Cell density did not affect any printing outcomes despite slight rheological changes. Printing outcomes were dominated by the speed ratio, with feedrate, flowrate, and cell density having little impact on printing outcomes when controlling for speed ratio within the ranges tested. The relevance of these results to other bioinks and printing conditions requires continued investigation by the bioprinting community, as well as highlight speed ratio as a key variable to report and suggest that rheology is a more sensitive measure than printing outcomes.

| S-EPMC7780841 | biostudies-literature

Biobased Acrylate Photocurable Resin Formulation for Stereolithography 3D Printing.

Project description:To facilitate the ongoing transition toward a circular economy, the availability of renewable materials for additive manufacturing becomes increasingly important. Here, we report the successful fabrication of complex shaped prototypes from biobased acrylate photopolymer resins, employing a commercial stereolithography apparatus (SLA) 3D printer. Four distinct resins with a biobased content ranging from 34 to 67% have been developed. All formulations demonstrated adequate viscosity and were readily polymerizable by the UV-laser-based SLA process. Increasing the double-bond concentration within the resin results in stiff and thermally resilient 3D printed products. High-viscosity resins lead to high-resolution prototypes with a complex microarchitecture and excellent surface finishing, comparable to commercial nonrenewable resins. These advances can facilitate the wide application of biobased resins for construction of new sustainable products via stereolithographic 3D printing methods.

| S-EPMC6641428 | biostudies-literature

Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs.

Project description:Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, which can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, we developed a gold nanorod (GNR) incorporated gelatin methacryloyl (GelMA)-based bioink for printing 3D functional cardiac tissue constructs. The GNR concentration was adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentration of GNR, the nanocomposite bioink had a low viscosity, similar to pristine inks, which allowed for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution was possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells showed improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridged the electrically resistant pore walls of polymers, improved the cell-to-cell coupling, and promoted synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.

| S-EPMC6181228 | biostudies-literature

Dendritic Hydrogel Bioink for 3D Printing of Bacterial Microhabitat.

Project description:A glucose-modified dendritic hydrogel is used as a bioink for bacterial encapsulation. This biocompatible hydrogel is a potentially suitable alternative to conventional alginate hydrogel for bacterial encapsulation, as it readily forms gel in the presence of Na+ or K+ ions without any additional stimuli such as pH, temperature, sonication, or the presence of divalent metal ions. We created a bacterial microhabitat by adding the gelator to phosphate-buffered saline containing live bacteria at physiological pH and using an additive three-dimensional (3D) printing technique. The bacteria remained viable and metabolically active within the 3D printed bacterial microhabitat, as shown with confocal laser scanning microscopy (CLSM) and scanning electrochemical microscopy (SECM).

| S-EPMC7266169 | biostudies-literature

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Project description:4D printing has the potential to create complex 3D geometries which are able to react to environmental stimuli opening new design possibilities. However, the vast majority of 4D printing approaches use polymer based materials, which limits the operational temperature. Here, we present a novel multi-metal electrochemical 3D printer which is able to fabricate bimetallic geometries and through the selective deposition of different metals, temperature responsive behaviour can thus be programmed into the printed structure. The concept is demonstrated through a meniscus confined electrochemical 3D printing approach with a multi-print head design with nickel and copper used as exemplar systems but this is transferable to other deposition solutions. Improvements in deposition speed (34% (Cu)-85% (Ni)) are demonstrated with an electrospun nanofibre nib compared to a sponge based approach as the medium for providing hydrostatic back pressure to balance surface tension in order to form a electrolyte meniscus stable. Scanning electron microscopy, X-ray computed tomography and energy dispersive X-ray spectroscopy shows that bimetallic structures with a tightly bound interface can be created, however convex cross sections are created due to uneven current density. Analysis of the thermo-mechanical properties of the printed strips shows that mechanical deformations can be generated in Cu-Ni strips at temperatures up to 300 °C which is due to the thermal expansion coefficient mismatch generating internal stresses in the printed structures. Electrical conductivity measurements show that the bimetallic structures have a conductivity between those of nanocrystalline copper (5.41 × 106 S.m-1) and nickel (8.2 × 105 S.m-1). The potential of this novel low-cost multi-metal 3D printing approach is demonstrated with the thermal actuation of an electrical circuit and a range of self-assembling structures.

| S-EPMC6408427 | biostudies-literature

Stereolithography 3D Printing of Lignin-Reinforced Composites with Enhanced Mechanical Properties.

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| S-EPMC6893962 | biostudies-literature

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