Photo-crosslinkable hydrogels, in particular gelatin methacryloyl (GelMa), are gaining increasing importance in biofabrication and tissue engineering. While GelMa is often described as mechanically ...'tunable', clear relationships linking the photocrosslinking conditions to reaction rates, and the resulting mechanical properties, have not been described. Meanwhile the conditions employed in the literature are disparate, and difficult to compare. In this work, in situ rheological measurements were used to quantify the relative rate of reaction of GelMa hydrogels with respect to light intensity, exposure time and photo-initiator concentration. In addition the UV degradation of the photo-initiator Irgacure 2959 was measured by UV-vis spectroscopy, and used to estimate the rate of free radical production as a function of light exposure. Using these data an expression was derived which predicts the mechanical properties of GelMa hydrogels produced across a wide range of crosslinking conditions. The model was validated through fabrication of a GelMa gradient which matched predicted properties. Human mesenchymal stem cells encapsulated in crosslinked GelMa exhibited high (>90%) viability post encapsulation, however metabolic activity over one week was influenced by the intensity of light used during crosslinking. The expressions described may be used to aid rational choices of GelMa photocrosslinking conditions, especially in cell encapsulation experiments where minimising the cytotoxic elements in the reaction is a priority.
Three-dimensional (3D) bioprinting is driving major innovations in the area of cartilage tissue engineering. Extrusion-based 3D bioprinting necessitates a phase change from a liquid bioink to a ...semi-solid crosslinked network achieved by a photo-initiated free radical polymerization reaction that is known to be cytotoxic. Therefore, the choice of the photocuring conditions has to be carefully addressed to generate a structure stiff enough to withstand the forces phisiologically applied on articular cartilage, while ensuring adequate cell survival for functional chondral repair. We recently developed a handheld 3D printer called "Biopen". To progress towards translating this freeform biofabrication tool into clinical practice, we aimed to define the ideal bioprinting conditions that would deliver a scaffold with high cell viability and structural stiffness relevant for chondral repair. To fulfill those criteria, free radical cytotoxicity was confined by a co-axial Core/Shell separation. This system allowed the generation of Core/Shell GelMa/HAMa bioscaffolds with stiffness of 200KPa, achieved after only 10 seconds of exposure to 700 mW/cm
of 365 nm UV-A, containing >90% viable stem cells that retained proliferative capacity. Overall, the Core/Shell handheld 3D bioprinting strategy enabled rapid generation of high modulus bioscaffolds with high cell viability, with potential for in situ surgical cartilage engineering.
Purpose
Bone tumours must be surgically excised in one piece with a margin of healthy tissue. The unique nature of each bone tumour case is well suited to the use of patient-specific implants, with ...additive manufacturing allowing production of highly complex geometries. This work represents the first assessment of the combination of surgical robotics and patient-specific additively manufactured implants.
Methods
The development and evaluation of a robotic system for bone tumour excision, capable of milling complex osteotomy paths, is described. The developed system was evaluated as part of an animal trial on 24 adult male sheep, in which robotic bone excision of the distal femur was followed by placement of patient-specific implants with operative time evaluated. Assessment of implant placement accuracy was completed based on post-operative CT scans.
Results
A mean overall implant position error of 1.05 ± 0.53 mm was achieved, in combination with a mean orientation error of 2.38 ± 0.98°. A mean procedure time (from access to implantation, excluding opening and closing) of 89.3 ± 25.25 min was observed, with recorded surgical time between 58 and 133 min, with this approximately evenly divided between robotic (43.9 ± 15.32) and implant-based (45.4 ± 18.97) tasks.
Conclusions
This work demonstrates the ability for robotics to achieve repeatable and precise removal of complex bone volumes of the type that would allow en bloc removal of a bone tumour. These robotically created volumes can be precisely filled with additively manufactured patient-specific implants, with minimal gap between cut surface and implant interface.
For decades, the study of tissue-engineered skeletal muscle has been driven by a clinical need to treat neuromuscular diseases and volumetric muscle loss. The in vitro fabrication of muscle offers ...the opportunity to test drug-and cell-based therapies, to study disease processes, and to perhaps, one day, serve as a muscle graft for reconstructive surgery. This study developed a biofabrication technique to engineer muscle for research and clinical applications. A bioprinting protocol was established to deliver primary mouse myoblasts in a gelatin methacryloyl (GelMA) bioink, which was implanted in an in vivo chamber in a nude rat model. For the first time, this work demonstrated the phenomenon of myoblast migration through the bioprinted GelMA scaffold with cells spontaneously forming fibers on the surface of the material. This enabled advanced maturation and facilitated the connection between incoming vessels and nerve axons in vivo without the hindrance of a scaffold material. Immunohistochemistry revealed the hallmarks of tissue maturity with sarcomeric striations and peripherally placed nuclei in the organized bundles of muscle fibers. Such engineered muscle autografts could, with further structural development, eventually be used for surgical reconstructive purposes while the methodology presented here specifically has wide applications for in vitro and in vivo neuromuscular function and disease modelling.
Abstract While micro-FE simulations have become a standard tool in computational biomechanics, the choice of appropriate material properties is still a relevant topic, typically involving empirical ...grey value-to-elastic modulus relations. We here derive the voxel-specific volume fractions of mineral, collagen, and water, from tissue-independent bilinear relations between mineral and collagen content in extracellular bone tissue (J. Theor. Biol. 287: 115, 2011), and from the measured X-ray attenuation information quantified in terms of grey values. The aforementioned volume fractions enter a micromechanics representation of bone tissue, as to deliver voxel-specific stiffness tensors. In order to check the relevance of this strategy, we convert a micro Computer Tomograph of a mouse femur into a regular Finite Element mesh, apply forces related to the dead load of a standing mouse, and then compare simulation results based on voxel-specific heterogeneous elastic properties to results based on homogeneous elastic properties related to the spatial average over the solid bone matrix compartment, of the X-ray attenuation coefficients. The element-specific strain energy density illustrates that use of homogeneous elastic properties implies overestimation of the organ stiffness. Moreover, the simulation reveals large tensile normal stresses throughout the femur neck, which may explain the mouse femur neck's trabecular morphology being quite different from the human case, where the femur neck bears compressive forces and bending moments.
Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three‐dimensional (3D) printing is an exciting and innovative ...biofabrication technology that enables the surgeon to deliver tissue‐engineering techniques at the time and location of need. We have created a hand‐held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single‐session surgery. This pilot study assessed the ability of the biopen to repair a full‐thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical‐sized full‐thickness chondral defect was created in the weight‐bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand‐held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench‐based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra‐ or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real‐time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.
To quantify the moulding ability of Plaster of Paris and polyester cast materials as assessed by the novel use of peripheral quantitative computed tomography.
A prospective crossover study was ...performed in 25 healthy volunteers aged 18–65 years. Participants’ non-dominant wrist was immobilized using a synthetic polyester cast followed by a Plaster of Paris cast with three point moulding to simulate reduction of a dorsally angulated distal radius fracture. The novel use of peripheral quantitative computed tomography was used to measure the closeness of fit of each cast on an axial tomographic slice.
Plaster of Paris casts were able to achieve a closer mould than polyester when measured between the bone and the cast (p=0.002), as well as between the skin and the cast (p=0.001). There was no difference when stratified on BMI. Using pQCT assessment, a closely moulded fit was able to be more consistently achieved when using Plaster of Paris when compared to polyester casts of the distal radius.
III.
Abstract Bone is a dynamic and hierarchical porous material whose spatial and temporal mechanical properties can vary considerably due to differences in its microstructure and due to remodeling. ...Hence, a multiscale analytical approach, which combines bone structural information at multiple scales to the remodeling cellular activities, could form an efficient, accurate and beneficial framework for the prognosis of changes in bone properties due to, e.g., bone diseases. In this study, an analytical formulation of bone remodeling integrated with multiscale micromechanical models is proposed to investigate the effects of structural changes at the nanometer level (collagen scale) on those at higher levels (tissue scale). Specific goals of this study are to derive a mechanical stimulus sensed by the osteocytes using a multiscale framework, to test the accuracy of the multiscale model for the prediction of bone density, and to demonstrate its multiscale capabilities by predicting changes in bone density due to changes occurring at the molecular level. At each different level, the bone composition was modeled as a two-phase material which made it possible to: 1) find a closed-form solution for the energy-based mechanical stimulus sensed by the osteocytes and 2) describe the anisotropic elastic properties at higher levels as a function of the stiffness of the elementary components (collagen, hydroxyapatite and water) at lower levels. The accuracy of the proposed multiscale model of bone remodeling was tested first by comparing the analytical bone volume fraction predictions to those obtained from the corresponding μFE-based computational model. Differences between analytical and numerical predictions were less than 1% while the computational time was drastically reduced, namely by a factor of 1 million. In a further analysis, the effects of changes in collagen and hydroxyapatite volume fractions on the bone remodeling process were simulated, and it was found that such changes considerably affect the bone density at the millimeter scale. In fact, smaller tissue density induces remodeling activities leading to finally higher overall bone density. The multiscale analytical model proposed in this study potentially provides an accurate and efficient tool for simulating patient-specific bone remodeling, which might be of importance in particular for the hip and spine, where an accurate assessment of bone micro-architecture is not possible.
A Robotic Tunnel Drainage Inspection Rover Hofer, Wolfgang; Zagar, Bernhard G.; Schachinger, Tobias ...
Transportation research procedia (Online),
2023, 2023-00-00, Letnik:
72
Journal Article
Odprti dostop
Drainage pipes in tunnels are very complicated to service but still need rather frequent inspections in order to detect the initiation of deposited scales stemming from carbonate that tends to ...precipitate when the pH-value of the mountain water rises with the release of gaseous carbon dioxide CO2 due to a decreasing water pressure. The drainages enable to design tunnels without resistance to ground water pressure. We present the development of a robot able to autonomously navigate through tunnel drainage pipe systems inspecting for these carbonate scale deposits, and can demonstrate that the currently available test platform is able to traverse autonomously, in between two recharging stops in manholes, a few hundred meters of tunnel pipes thereby acquiring on a localized basis various environmental parameters like pH-value, the water's conductivity, temperature, carbon dioxide concentration in addition to documenting the pipes’ condition with respect to scaling via a video clip that is recorded along with an estimated position in the pipe.
In recent years, new technologies based on 3D bioprinting have emerged as ideal tools with which to arrange cells and biomaterials in three dimensions and so achieve tissue engineering's original ...goals. The simplest and most widely used form of bioprinting is based on pneumatic extrusion, where 3D structures are built up by drawing patterns of cell-laden or non-cell-laden material through a robotically manipulated syringe. Developing and characterizing new biomaterials for 3D bioprinting (i.e., bioinks) is critical for the progress of the field. This chapter describes a series of protocols for developing, optimizing, and testing new bioinks for extrusion-based 3D bioprinting.
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