| 1. |
- Bondesson, Johan, 1991, et al.
(author)
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Definition of Tubular Anatomic Structures from Arbitrary Stereo Lithographic Surface
- 2017
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In: Initiative Seminar Engineering Health, 8-9 November 2017, Chalmers.
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Conference paper (other academic/artistic)abstract
- An accurate description of anatomies and dynamics of vessels is crucial to understand their characteristics and improve surgical techniques, thus it is the basis, in addition to surgeon experience, on which stent design and operation procedures rely. The process of producing this description is user intensive, and recent improvement in image processing of medical3D imaging allows for a more automated workflow. However, there is a need to bridge the gap from a processed geometry to a robust mathematical computational grid. By sequentially segmenting a tubular anatomic structure, here defined by a stereo lithographic (STL) surface, an initial centerline is formed by connecting centroids of orthogonal cross-sectional contours along the length of the structure. Relying on the initial centerline, a set of non-overlapping 2D cross sectional contours are defined along the centerline, a centerline which is updated after the 2D contours are produced. After a second iteration of producing 2D contours and updating the centerline, a full description of the structure is created. Our method for describing vessel geometry shows good coherence to existing method. The main advantages of our method include the possibility of having arbitrary triangulated STL surface input, automated centerline definition, safety against intersecting cross-sectional contours and automatic clean-up of local kinks and wrinkles.
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| 2. |
- Palmquist, Anders, 1977, et al.
(author)
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Complex geometry and integrated macro-porosity: Clinical applications of electron beam melting to fabricate bespoke bone-anchored implants
- 2023
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In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 156, s. 125-145
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Research review (peer-reviewed)abstract
- The last decade has witnessed rapid advancements in manufacturing technologies for biomedical implants. Additive manufacturing (or 3D printing) has broken down major barriers in the way of producing complex 3D geometries. Electron beam melting (EBM) is one such 3D printing process applicable to metals and alloys. EBM offers build rates up to two orders of magnitude greater than comparable laser-based technologies and a high vacuum environment to prevent accumulation of trace elements. These features make EBM particularly advantageous for materials susceptible to spontaneous oxidation and nitrogen pick-up when exposed to air (e.g., titanium and titanium-based alloys). For skeletal reconstruction(s), anatomical mimickry and integrated macro-porous architecture to facilitate bone ingrowth are undoubtedly the key features of EBM manufactured implants. Using finite element modelling of physiological loading conditions, the design of a prosthesis may be further personalised. This review looks at the many unique clinical applications of EBM in skeletal repair and the ground-breaking innovations in prosthetic rehabilitation. From a simple acetabular cup to the fifth toe, from the hand-wrist complex to the shoulder, and from vertebral replacement to cranio-maxillofacial reconstruction, EBM has experienced it all. While sternocostal reconstructions might be rare, the repair of long bones using EBM manufactured implants is becoming exceedingly frequent. Despite the various merits, several challenges remain yet untackled. Nevertheless, with the capability to produce osseointegrating implants of any conceivable shape/size, and permissive of bone ingrowth and functional loading, EBM can pave the way for numerous fascinating and novel applications in skeletal repair, regeneration, and rehabilitation. Statement of significance: Electron beam melting (EBM) offers unparalleled possibilities in producing contaminant-free, complex and intricate geometries from alloys of biomedical interest, including Ti6Al4V and CoCr. We review the diverse range of clinical applications of EBM in skeletal repair, both as mass produced off-the-shelf implants and personalised, patient-specific prostheses. From replacing large volumes of disease-affected bone to complex, multi-material reconstructions, almost every part of the human skeleton has been replaced with an EBM manufactured analog to achieve macroscopic anatomical-mimickry. However, various questions regarding long-term performance of patient-specific implants remain unaddressed. Directions for further development include designing personalised implants and prostheses based on simulated loading conditions and accounting for trabecular bone microstructure with respect to physiological factors such as patient's age and disease status.
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| 3. |
- Johansson, Martin L, et al.
(author)
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Non-invasive sampling procedure revealing the molecular events at different abutments of bone-anchored hearing systems–A prospective clinical pilot study
- 2022
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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the molecular activities in different compartments around the bone-anchored hearing system (BAHS) with either electropolished or machined abutments and to correlate these activities with clinical and microbiological findings. Materials and methods: Twelve patients received machined or electropolished abutments after implant installation of BAHS. Peri-abutment fluid and tissue were collected from baseline to 12 months. Gene expression of cytokines and factors related to tissue healing and inflammation, regeneration and remodelling, as well as bacterial recognition were determined using quantitative-polymerase chain reaction (qPCR). The clinical status was evaluated using the Holgers scoring system, and bacterial colonisation was investigated by culturing. Results: The gene expression of inflammatory cytokines (IL-8, IL-1β, and IL-10) and bacteria-related Toll-like receptors (2 and 4) was higher in the peri-abutment fluid than at baseline and in the peri-abutment tissue at 3 and 12 months. Conversely, the expression of genes related to tissue regeneration (Coll1a1 and FOXO1) was higher in the tissue samples than in the peri-abutment fluid at 3 and 12 months. Electropolished abutments triggered higher expression of inflammatory cytokines (IL-8 and IL-1β) (in peri-abutment fluid) and regeneration factor FOXO1 (in peri-abutment tissue) than machined abutments. Several cytokine genes in the peri-abutment fluid correlated positively with the detection of aerobes, anaerobes and Staphylococcus species, as well as with high Holger scores. Conclusion: This study provides unprecedented molecular information on the biological processes of BAHS. Despite being apparently healed, the peri-abutment fluid harbours prolonged inflammatory activity in conjunction with the presence of different bacterial species. An electropolished abutment surface appears to be associated with stronger proinflammatory activity than that with a machined surface. The analysis of the peri-abutment fluid deserves further verification as a non-invasive sampling and diagnostic procedure of BAHS.
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| 4. |
- Pirozzi, Ileana, et al.
(author)
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Circulatory Support : Artificial Muscles for the Future of Cardiovascular Assist Devices
- 2023
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In: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095.
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Journal article (peer-reviewed)abstract
- Artificial muscles enable the design of soft implantable devices which are poised to transform the way we mechanically support the heart today. Heart failure is a prevalent and deadly disease, which is treated with the implantation of rotary blood pumps as the only alternative to heart transplantation. The clinically used mechanical devices are associated with severe adverse events, which are reflected here in a comprehensive list of critical requirements for soft active devices of the future: low power, no blood contact, pulsatile support, physiological responsiveness, high cycle life, and less-invasive implantation. In this review, we investigate and critically evaluate prior art in artificial muscles for their applicability in the short and long term. We highlight the main challenges regarding the effectiveness, controllability, and implantability of recently proposed actuators and explore future perspectives for attachment, physiological responsiveness, durability, and biodegradability as well as equitable design considerations.
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| 5. |
- Lammi, Mikko J., 1961-, et al.
(author)
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Regulation of oxygen tension as a strategy to control chondrocytic phenotype for cartilage tissue engineering and regeneration
- 2024
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In: Bioengineering. - : MDPI. - 2306-5354. ; 11:3
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Research review (peer-reviewed)abstract
- Cartilage defects and osteoarthritis are health problems which are major burdens on health care systems globally, especially in aging populations. Cartilage is a vulnerable tissue, which generally faces a progressive degenerative process when injured. This makes it the 11th most common cause of global disability. Conservative methods are used to treat the initial phases of the illness, while orthopedic management is the method used for more progressed phases. These include, for instance, arthroscopic shaving, microfracturing and mosaicplasty, and joint replacement as the final treatment. Cell-based implantation methods have also been developed. Despite reports of successful treatments, they often suffer from the non-optimal nature of chondrocyte phenotype in the repair tissue. Thus, improved strategies to control the phenotype of the regenerating cells are needed. Avascular tissue cartilage relies on diffusion for nutrients acquisition and the removal of metabolic waste products. A low oxygen content is also present in cartilage, and the chondrocytes are, in fact, well adapted to it. Therefore, this raises an idea that the regulation of oxygen tension could be a strategy to control the chondrocyte phenotype expression, important in cartilage tissue for regenerative purposes. This narrative review discusses the aspects related to oxygen tension in the metabolism and regulation of articular and growth plate chondrocytes and progenitor cell phenotypes, and the role of some microenvironmental factors as regulators of chondrocytes.
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| 6. |
- Ortiz Catalan, Max Jair, 1982, et al.
(author)
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Patterned Stimulation of Peripheral Nerves Produces Natural Sensations With Regards to Location but Not Quality
- 2019
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In: IEEE Transactions on Medical Robotics and Bionics. - 2576-3202. ; 1:3, s. 199-203
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Journal article (peer-reviewed)abstract
- Sensory feedback is crucial for dexterous manipulation and sense of ownership. Electrical stimulation of severed afferent fibers due to an amputation elicits referred sensations in the missing limb. However, these sensations are commonly reported with a concurrent “electric” or “tingling” character (paresthesia). In this paper, we examined the effect of modulating different pulse parameters on the quality of perceived sensations. Three subjects with above-elbow amputation were implanted with cuff electrodes and stimulated with a train of pulses modulated in either amplitude, width, or frequency (“patterned stimulation”). Pulses were shaped using a slower carrier wave or via quasi-random generation. Subjects were asked to evaluate the natural quality of the resulting sensations using a numeric rating scale. We found that the location of the percepts was distally referred and somatotopically congruent, but their quality remained largely perceived as artificial despite employing patterned modulation. Sensations perceived as arising from the missing limb are intuitive and natural with respect to their location and, therefore, useful for functional restoration. However, our results indicate that sensory transformation from paresthesia to natural qualia seems to require more than patterned stimulation.
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| 7. |
- Cardemil, Carina, et al.
(author)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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In: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Journal article (peer-reviewed)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 8. |
- Enejder, Annika, 1969, et al.
(author)
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SHG Imaging for Tissue Engineering Applications
- 2016
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In: Second Harmonic Generation Imaging. - : CRC Press. - 9781439849156 - 9781439849149 ; , s. 409-426
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Book chapter (other academic/artistic)abstract
- Treatment of lost tissue oen relies on transplantations, either of donor or of autologous tissue. Both alternatives have limitations; there is for example a limited supply of donor transplants, which also require immunosuppression therapy with possible side eects. Transplanted autologous tissue may lack some of the functions of the original tissue and the procedure may also introduce complications at the donor site. In some cases, articial substitutes manufactured from nonbiological materials can be used, for example, synthetic polymer blood vessels or joint replacement prostheses. However, these replacements have drawbacks such as risk for infections, limited material durability, and lack of mechanisms for repair, growth, and remodeling. For these reasons, development of advanced articial tissue constructs with adaptive capabilities is desirable.
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| 9. |
- Isaksson-Daun, Johan
(author)
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A Sound Approach Toward a Mobility Aid for Blind and Low-Vision Individuals
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Reduced independent mobility of blind and low-vision individuals (BLVIs) cause considerable societal cost, burden on relatives, and reduced quality of life for the individuals, including increased anxiety, depression symptoms, need of assistance, risk of falls, and mortality. Despite the numerous electronic travel aids proposed since at least the 1940’s, along with ever-advancing technology, the mobility issues persist. A substantial reason for this is likely several and severe shortcomings of the field, both in regards to aid design and evaluation.In this work, these shortcomings are addressed with a generic design model called Desire of Use (DoU), which describes the desire of a given user to use an aid for a given activity. It is then applied on mobility of BLVIs (DoU-MoB), to systematically illuminate and structure possibly all related aspects that such an aid needs to aptly deal with, in order for it to become an adequate aid for the objective. These aspects can then both guide user-centered design as well as choice of test methods and measures.One such measure is then demonstrated in the Desire of Use Questionnaire for Mobility of Blind and Low-Vision Individuals (DoUQ-MoB), an aid-agnostic and comprehensive patient-reported outcome measure. The question construction originates from the DoU-MoB to ensure an encompassing focus on mobility of BLVIs, something that has been missing in the field. Since it is aid-agnostic it facilitates aid comparison, which it also actively promotes. To support the reliability of the DoUQ-MoB, it utilizes the best known practices of questionnaire design and has been validated once with eight orientation and mobility professionals, and six BLVIs. Based on this, the questionnaire has also been revised once.To allow for relevant and reproducible methodology, another tool presented herein is a portable virtual reality (VR) system called the Parrot-VR. It uses a hybrid control scheme of absolute rotation by tracking the user’s head in reality, affording intuitive turning; and relative movement where simple button presses on a controller moves the virtual avatar forward and backward, allowing for large-scale traversal while not walking physically. VR provides excellent reproducibility, making various aggregate movement analysis feasible, while it is also inherently safe. Meanwhile, the portability of the system facilitates testing near the participants, substantially increasing the number of potential blind and low-vision recruits for user tests.The thesis also gives a short account on the state of long-term testing in the field; it being short is mainly due to that there is not much to report. It then provides an initial investigation into possible outcome measures for such tests by taking instruments in use by Swedish orientation and mobility professionals as a starting point. Two of these are also piloted in an initial single-session trial with 19 BLVIs, and could plausibly be used for long-term tests after further evaluation.Finally, a discussion is presented regarding the Audomni project — the development of a primary mobility aid for BLVIs. Audomni is a visuo-auditory sensory supplementation device, which aims to take visual information and translate it to sound. A wide field-of-view, 3D-depth camera records the environment, which is then transformed to audio through the sonification algorithms of Audomni, and finally presented in a pair of open-ear headphones that do not block out environmental sounds. The design of Audomni leverages the DoU-MoB to ensure user-centric development and evaluation, in the aim of reaching an aid with such form and function that it grants the users better mobility, while the users still want to use it.Audomni has been evaluated with user tests twice, once in pilot tests with two BLVIs, and once in VR with a heterogenous set of 19 BLVIs, utilizing the Parrot-VR and the DoUQ-MoB. 76 % of responders (13 / 17) answered that it was very or extremely likely that they would want use Audomni along with their current aid. This might be the first result in the field demonstrating a majority of blind and low-vision participants reporting that they actually want to use a new electronic travel aid. This shows promise that eventual long-term tests will demonstrate an increased mobility of blind and low-vision users — the overarching project aim. Such results would ultimately mean that Audomni can become an aid that alleviates societal cost, reduces burden on relatives, and improves users’ quality of life and independence.
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| 10. |
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| 11. |
- Márquez, Juan Carlos, et al.
(author)
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Textrode functional straps for bioimpedance measurements-experimental results for body composition analysis
- 2013
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In: European Journal of Clinical Nutrition. - : Nature Publishing Group. - 0954-3007 .- 1476-5640. ; 67:Suppl 1, s. 22-27
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Journal article (peer-reviewed)abstract
- Background/Objectives:Functional garments for physiological sensing purposes have been used in several disciplines, that is, sports, firefighting, military and medicine. In most of the cases, textile electrodes (textrodes) embedded in the garment are used to monitor vital signs and other physiological measurements. Electrical bioimpedance (EBI) is a non-invasive and effective technology that can be used for the detection and supervision of different health conditions.EBI technology could make use of the advantages of garment integration; however, a successful implementation of EBI technology depends on the good performance of textrodes. The main drawback of textrodes is a deficient skin-electrode interface that produces a high degree of sensitivity to signal disturbances. This sensitivity can be reduced with a suitable selection of the electrode material and an intelligent and ergonomic garment design that ensures an effective skin-electrode contact area.Subjects/Methods:In this work, textrode functional straps for total right side EBI measurements for body composition are presented, and its measurement performance is compared against the use of Ag/AgCl electrodes. Shieldex sensor fabric and a tetra-polar electrode configuration using the ImpediMed spectrometer SFB7 in the frequency range of 3-500 kHz were used to obtain and analyse the impedance spectra and Cole and body composition parameters.Results:The results obtained show stable and reliable measurements; the slight differences obtained with the functional garment do not significantly affect the computation of Cole and body composition parameters.Conclusions:The use of a larger sensor area, a high conductive material and an appropriate design can compensate, to some degree, for the charge transfer deficiency of the skin-electrode interface.
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| 12. |
- Capece, Sabrina, et al.
(author)
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A general strategy for obtaining biodegradable polymer shelled microbubbles as theranostic devices
- 2013
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In: Chemical Communications. - 1359-7345 .- 1364-548X. ; 49:51, s. 5763-5765
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Journal article (peer-reviewed)abstract
- Fabrication of multifunctional ultrasound contrast agents (UCAs) has been recently addressed by several research groups. A versatile strategy for the synthesis of UCA precursors in the form of biodegradable vesicles with a biocompatible crosslinked polymer shell is described. Upon ultrasound irradiation, acoustic droplet vaporization transforms such particles into microbubbles behaving as UCAs. This proof of concept entails the features of a potential theranostic microdevice.
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| 13. |
- Surmeneva, Maria, et al.
(author)
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Investigation of the HA film deposited on the porous Ti6Al4V alloy prepared via additive manufacturing
- 2015
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In: IOP Conference Series. - IOP.
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Conference paper (peer-reviewed)abstract
- This study is focused on the use of radio frequency magnetron sputtering to modify the surface of porous Ti6Al4V alloy fabricated via additive manufacturing technology. The hydroxyapatite (HA) coated porous Ti6Al4V alloy was studied in respect with its chemical and phase composition, surface morphology, water contact angle and hysteresis, and surface free energy. Thin nanocrystalline HA film was deposited while its structure with diamond-shaped cells remained unchanged. Hysteresis and water contact angle measurements revealed an effect of the deposited HA films, namely an increased water contact angle and contact angle hysteresis. The increase of the contact angle of the coating-substrate system compared to the uncoated substrate was attributed to the multiscale structure of the resulted surfaces.
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| 14. |
- Andersson, Helene, 1983, et al.
(author)
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Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films
- 2013
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 48:1-2, s. 240-248
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Journal article (peer-reviewed)abstract
- Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the films after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.
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| 15. |
- Grishenkov, Dmitry, 1983-, et al.
(author)
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In search of the optimal ultrasound heart perfusion imaging platform
- 2015
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In: Journal of ultrasound in medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 34:9, s. 1599-1605
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Journal article (peer-reviewed)abstract
- ObjectiveQuantification of the myocardial perfusion by contrast echocardiography (CEC) remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled.MethodsTo contribute towards an improvement, we developed a CEC perfusion imaging platform based on isolated rat heart coupled to the ultrasound scanner. Perfusion was assessed using three different types of contrast agent: dextran-based Promiten®, phospholipid-shelled SonoVue®, and polymer-shelled MB-pH5-RT. The myocardial video-intensity was monitored over time from contrast administration to peak and two characteristic constants were calculated using exponential fit (A representing capillary volume and b representing inflow velocity).ResultsAcquired experimental evidence demonstrates that the application of all three types of contrast agent allow ultrasonic estimation of myocardial perfusion in the isolated rat heart. Video-intensity maps show that an increase in contrast concentration increases the late plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to Axb, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by the flowmeter attached to the aortic cannula.ConclusionsThe described CEC perfusion imaging platform holds promise for standardized evaluation and optimization of ultrasound contrast perfusion imaging where real time inflow curves at low acoustic power semi-quantitatively reflect coronary flow.
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| 16. |
- Kothapalli, Veera Venkata Satya Naray, 1985-, et al.
(author)
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Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent : An acoustic characterization and optical visualization
- 2014
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In: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - 0885-3010 .- 1525-8955. ; 62:3, s. 451-462
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Journal article (peer-reviewed)abstract
- This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.
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| 17. |
- Martinez Avila, Hector, 1985
(author)
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Biofabrication, Biomechanics and Biocompatibility of Nanocellulose-based Scaffolds for Auricular Cartilage Regeneration
- 2015
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Doctoral thesis (other academic/artistic)abstract
- In about 2:10,000 births the external part of the ear, the auricle, is severely malformed or absent. Furthermore, tumors and trauma can cause defects to the auricle. For patients with dysplasia of the auricle, and especially for children, an inconspicuous outer appearance with life-like auricles is important for their psychological and emotional well being as well as their psycho-social development. Auricular reconstruction remains a great challenge due to the complexity of surgical reconstruction using rib cartilage. Despite the advances in stem cell technology and biomaterials, auricular cartilage tissue engineering (TE) is still in an early stage of development due to critical requirements demanding appropriate mechanical properties and shape stability of the tissue-engineered construct. This thesis has focused on developing patient-specific tissue-engineered auricles for one-step surgery using a novel biomaterial, bacterial nanocellulose (BNC), seeded with human nasoseptal chondrocytes (hNC) and bone marrow mononuclear cells (MNC).Biomechanical properties of human auricle cartilage were measured and used as a benchmark for tuning BNC properties. In order to meet the biomechanical requirements, a scaffold with bilayer architecture composed of a dense BNC support layer and a macroporous structure was designed. Firstly, the biocompatibility of the dense BNC layer was investigated, demonstrating a minimal foreign body response according to standards set forth in ISO 10993. Secondly, different methods to create macroporous BNC scaffolds were studied and the redifferentiation capacity of hNCs was evaluated in vitro; revealing that macroporous BNC scaffolds support cell ingrowth, proliferation and neocartilage formation. The bilayer BNC scaffold was biofabricated and tested for endotoxins and cytotoxicity before evaluating in long-term 3D culture, and subsequently in vivo for eight weeks—in an immunocompromised animal model. The results demonstrated that the non-pyrogenic and non- cytotoxic bilayer BNC scaffold offers a good mechanical stability and maintains a structural integrity, while providing a porous 3D environment that is suitable for hNCs and MNCs to produce neocartilage, in vitro and in vivo. Furthermore, patient-specific auricular BNC scaffolds with bilayer architecture were biofabricated and seeded with autologous rabbit auricular chondrocytes (rAC) for implantation in an immunocompetent rabbit model for six weeks. The results demonstrated the shape stability of the rAC-seeded scaffolds and neocartilage depositions in the immunocompetent autologous grafts. 3D bioprinting was also evaluated for biofabrication of patient-specific, chondrocyte-laden auricular constructs using a bioink composed of nanofibrillated cellulose and alginate. Bioprinted auricular constructs showed an excellent shape and size stability after in vitro culture. Moreover, this bioink supports redifferentiation of hNCs while offering excellent printability, making this a promising approach for auricular cartilage TE. Furthermore, the use of bioreactors is essential for the development of tissue-engineered cartilage in vitro. Thus, a compression bioreactor was utilized to apply dynamic mechanical stimulation to cell-seeded constructs as a means to enhance production of extracellular matrix in vitro.In this work, a potential clinical therapy for auricular reconstruction using tissue-engineered auricles is demonstrated; where BNC is proposed as a promising non-degradable biomaterial with good chemical and mechanical stability for auricular cartilage TE. Although the primary focus of this thesis is on auricular reconstruction, the methods developed are also applicable in the regeneration of other cartilage tissues such as those found in the nose, trachea, spine and articular joints.
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| 18. |
- Pettersen, Emily, 1996, et al.
(author)
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Enhancing osteoblast survival through pulsed electrical stimulation and implications for osseointegration
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Electrical stimulation has been suggested as a means for promoting the direct structural and functional bonding of bone tissue to an artificial implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for inducing an electric field with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72 h at two different pulse amplitudes (10 mu A and 20 mu A) and at two different frequencies (50 Hz and 100 Hz). We found that asymmetric charge-balanced pulsed electrical stimulation improved cell survival and collagen production in a dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nerve stimulation has the potential to improve cell survival and may provide a promising approach to improve peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available.
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| 19. |
- Wu, Dan, 1990-, et al.
(author)
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Young’s modulus of trabecular bone at the tissue level : A review
- 2018
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In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 78, s. 1-12
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Research review (peer-reviewed)abstract
- The tissue-level Young’s modulus of trabecular bone is important for detailed mechanical analysis of bone and bone-implant mechanical interactions. However, the heterogeneity and small size of the trabecular struts complicate an accurate determination. Methods such as micro-mechanical testing of single trabeculae, ultrasonic testing, and nanoindentation have been used to estimate the trabecular Young’s modulus. This review summarizes and classifies the trabecular Young’s moduli reported in the literature. Information on species, anatomic site, and test condition of the samples has also been gathered. Advantages and disadvantages of the different methods together with recent developments are discussed, followed by some suggestions for potential improvement, for future work. In summary, this review provides a thorough introduction to the approaches used for determining trabecular Young’s modulus, highlights important considerations when applying these methods and summarizes the reported Young’s modulus for follow-up studies on trabecular properties.
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| 20. |
- Seijsing, Fredrik, et al.
(author)
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Recombinant spider silk coatings functionalized with enzymes targeting bacteria and biofilms
- 2020
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In: MicrobiologyOpen. - : Wiley. - 2045-8827. ; 9:4
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Journal article (peer-reviewed)abstract
- Bacteria forming biofilms on surgical implants is a problem that might be alleviated by the use of antibacterial coatings. In this article, recombinant spider silk was functionalized with the peptidoglycan degrading endolysin SAL-1 from the staphylococcal bacteriophage SAP-1 and the biofilm-matrix-degrading enzyme Dispersin B from Aggregatibacter actinomycetemcomitans using direct genetic fusion and/or covalent protein–protein fusion catalyzed by Sortase A. Spider silk assembly and enzyme immobilization was monitored using quartz crystal microbalance analysis. Enzyme activity was investigated both with a biochemical assay using cleavage of fluorescent substrate analogues and bacterial assays for biofilm degradation and turbidity reduction. Spider silk coatings functionalized with SAL-1 and Disperin B were found to exhibit bacteriolytic effect and inhibit biofilm formation, respectively. The strategy to immobilize antibacterial enzymes to spider silk presented herein show potential to be used as surface coatings of surgical implants and other medical equipment to avoid bacterial colonization.
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| 21. |
- Biswas, Tuser, 1988-, et al.
(author)
-
Digital inkjet printing of antimicrobial lysozyme on pretreated polyester fabric
- 2022
-
Conference paper (peer-reviewed)abstract
- Lysozyme was inkjet printed on two different polyester fabrics considering several challenges of printing enzymes on synthetic fabric surfaces. Wettability of both the fabrics were improved by alkaline pre-treatment resulting reduction in water contact angle to 60±2 from 95°±3 and to 80°±2 from 115°±2 for thinner and coarser fabric respectively. Activity of lysozyme in the prepared ink was 9240±34 units/ml and reduced to 5946±23 units/ml as of collected after jetting process (before printing on fabric). The formulated ink was effectively inkjet printed on alkali treated polyester fabric for antimicrobial applications. Retention of higher activity of the printed fabric requires further studies on enzyme-fibre binding mechanisms and understanding protein orientation on fabric surface after printing
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| 22. |
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| 23. |
- Oskarsdotter, Kristin, 1995, et al.
(author)
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Autologous endothelialisation by the stromal vascular fraction on laminin-bioconjugated nanocellulose-alginate scaffolds
- 2023
-
In: Biomedical Materials (Bristol). - 1748-605X .- 1748-6041. ; 18:4
-
Journal article (peer-reviewed)abstract
- Establishing a vascular network in biofabricated tissue grafts is essential for ensuring graft survival. Such networks are dependent on the ability of the scaffold material to facilitate endothelial cell adhesion; however, the clinical translation potential of tissue-engineered scaffolds is hindered by the lack of available autologous sources of vascular cells. Here, we present a novel approach to achieving autologous endothelialisation in nanocellulose-based scaffolds by using adipose tissue-derived vascular cells on nanocellulose-based scaffolds. We used sodium periodate-mediated bioconjugation to covalently bind laminin to the scaffold surface and isolated the stromal vascular fraction and endothelial progenitor cells (EPCs; CD31+CD45−) from human lipoaspirate. Additionally, we assessed the adhesive capacity of scaffold bioconjugation in vitro using both adipose tissue-derived cell populations and human umbilical vein endothelial cells. The results showed that the bioconjugated scaffold exhibited remarkably higher cell viability and scaffold surface coverage by adhesion regardless of cell type, whereas control groups comprising cells on non-bioconjugated scaffolds exhibited minimal cell adhesion across all cell types. Furthermore, on culture day 3, EPCs seeded on laminin-bioconjugated scaffolds showed positive immunofluorescence staining for the endothelial markers CD31 and CD34, suggesting that the scaffolds promoted progenitor differentiation into mature endothelial cells. These findings present a possible strategy for generating autologous vasculature and thereby increase the clinical relevance of 3D-bioprinted nanocellulose-based constructs.
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| 24. |
- Hansson, Magnus L., et al.
(author)
-
Artificial spider silk supports and guides neurite extension in vitro
- 2021
-
In: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:11
-
Journal article (peer-reviewed)abstract
- Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs.
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| 25. |
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| 26. |
- Procter, Philip, et al.
(author)
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Designing A Commercial Biomaterial For A Specific Unmet Clinical Need – : An Adhesive Odyssey
- 2018
-
Conference paper (peer-reviewed)abstract
- There are clinical situations in fracture repair, e.g. osteochondral fragments, where current implant hardware is insufficient. The proposition of an adhesive enabling fixation and healing has been considered but no successful candidate has emerged thus far. The many preclinical and few clinical attempts include fibrin glue, mussel adhesive and even “Kryptonite” (US bone void filler). The most promising recent attempts are based on phosphorylating amino acids, part of a common cellular adhesion mechanism linking mussels, caddis fly larvae, and mammals. Rapid high bond strength development in the wetted fatty environment of fractured bone, that is sustained during biological healing, is challenging to prove both safety and efficacy. Additionally, there are no “predicate” preclinical animal and human models which led the authors to develop novel evaluations for an adhesive candidate “OsStictm” based on calcium salts and amino acids. Adhesive formulations were evaluated in both soft (6/12 weeks) and hard tissue (3,7,10,14 & 42 days) safety studies in murine models. The feasibility of a novel adhesiveness test, initially proven in murine cadaver femoral bone, is being assessed in-vivo (3,7,10,14 & 42 days) in bilateral implantations with a standard tissue glue as the control. In parallel an ex-vivo human bone model using freshly harvested human donor bone is under development to underwrite the eventual clinical application of such an adhesive. This is part of a risk mitigation project bridging between laboratory biomaterial characterisation and a commercial biomaterial development where safety and effectiveness have to meet today´s new medical device requirements.
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| 27. |
- Pujari-Palmer, Michael, et al.
(author)
-
A Novel Class of Injectable Bioceramics That Glue Tissues and Biomaterials
- 2018
-
In: Materials. - : MDPI AG. - 1996-1944. ; 11:12
-
Journal article (peer-reviewed)abstract
- Calcium phosphate cements (CPCs) are clinically effective void fillers that are capable of bridging calcified tissue defects and facilitating regeneration. However, CPCs are completely synthetic/inorganic, unlike the calcium phosphate that is found in calcified tissues, and they lack an architectural organization, controlled assembly mechanisms, and have moderate biomechanical strength, which limits their clinical effectiveness. Herein, we describe a new class of bioinspired CPCs that can glue tissues together and bond tissues to metallic and polymeric biomaterials. Surprisingly, alpha tricalcium phosphate cements that are modified with simple phosphorylated amino acid monomers of phosphoserine (PM-CPCs) bond tissues up to 40-fold stronger (2.5-4 MPa) than commercial cyanoacrylates (0.1 MPa), and 100-fold stronger than surgical fibrin glue (0.04 MPa), when cured in wet-field conditions. In addition to adhesion, phosphoserine creates other novel properties in bioceramics, including a nanoscale organic/inorganic composite microstructure, and templating of nanoscale amorphous calcium phosphate nucleation. PM-CPCs are made of the biocompatible precursors calcium, phosphate, and amino acid, and these represent the first amorphous nano-ceramic composites that are stable in liquids.
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| 28. |
- Shah, Furqan A., et al.
(author)
-
Bioactive glass and glass-ceramic scaffolds for bone tissue engineering
- 2018
-
In: Bioactive Glasses (Second Edition). - 9780081009369 ; , s. 201-33
-
Book chapter (other academic/artistic)abstract
- Bioactive glasses and glass-ceramics are a diverse group of materials possessing a unique set of physicochemical properties that make them useful for bone repair. Scaffolds for bone tissue engineering are subject to many requirements including biocompatibility, osteogenesis, biodegradability, and mechanical competence, all of which must be considered in the design features. This chapter addresses various scaffold fabrication techniques for melt-derived and sol-gel-derived compositions, polymer-based organic-inorganic composites, calcium phosphate-based inorganic-inorganic composites, bioactive bone cements, scaffolds based on glass compositions containing specific therapeutic ions, and hybrid materials where the organic and inorganic phases interact at the molecular level. The most important achievements, challenges and potential solutions, as well as the most promising areas of future research involving bioactive glasses and glass-ceramics for bone tissue engineering are presented.
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| 29. |
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| 30. |
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| 31. |
- Wang, Nan, 1988, et al.
(author)
-
Improved Interfacial Bonding Strength and Reliability of Functionalized Graphene Oxide for Cement Reinforcement Applications
- 2020
-
In: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 26:29, s. 6561-6568
-
Journal article (peer-reviewed)abstract
- Poor bonding strength between nanomaterials and cement composites inevitably lead to the failure of reinforcement. Herein, a novel functionalization method for the fabrication of functionalized graphene oxide (FGO), which is capable of forming highly reliable covalent bonds with cement hydration products, and therefore, suitable for use as an efficient reinforcing agent for cement composites, is discussed. The bonding strength between cement and aggregates was improved more than 21 times with the reinforcement of FGO. The fabricated FGO also demonstrated many important features, including high reliability in cement pastes, good dispersibility, and efficient structural refinement of cement hydration products. With the incorporation of FGO, cement mortar samples demonstrated up to 40 % increased early and ultimate strength. Such results make the fast demolding and manufacture of light constructions become highly possible, and show strong advantages on improving productivity, saving cost, and reducing CO2 emissions in practical applications.
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| 32. |
- Pettersen, Emily, 1996, et al.
(author)
-
Electrical stimulation to promote osseointegration of bone anchoring implants: a topical review
- 2022
-
In: Journal of Neuroengineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 19:1
-
Journal article (peer-reviewed)abstract
- Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.
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| 33. |
- Metreveli, Giorgi, et al.
(author)
-
A Size-Exclusion Nanocellulose Filter Paper for Virus Removal
- 2014
-
In: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 10:3, s. 1546-1550
-
Journal article (peer-reviewed)abstract
- This is the first time a 100% natural, unmodified nanofibrous polymer-based membrane is demonstrated capable of removing viruses solely based on the size-exclusion principle, with log10 reduction value (LRV) ≥ 6.3 as limited by the assay lower detection limit and the feed virus titre, thereby matching the performance of industrial synthetic polymer virus removal filters.
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| 34. |
- Eriksson, Siw, et al.
(author)
-
Three-dimensional Fabrics as Medical Textiles
- 2015
-
In: Advances in 3D Textiles. - : Woodhead Publishing Limited. - 9781782422143 - 9781782422198 ; , s. 305-340
-
Book chapter (other academic/artistic)abstract
- The number of 3D textile applications in medicine is rapidly increasing as new technology and procedures are introduced in health care. A first estimate of current medical applications of both general and 3D textiles is presented based on the medical devices classification system established by the US Food and Drug Administration. The textile specifics for these applications are covered from a textile technique perspective where the different 3D weaving as well as knitting, braiding and non-woven techniques are described and how their properties they can contribute in medical applications. In addition, emerging opportunities based on smart textiles as part of textile systems are described on a general level. The strong application areas of 3D medical textiles, i.e. wound management, vascular grafting and scaffolding for tissue engineering are covered in detail both from the medical and textiles perspective. Finally, some future lines of development are suggested and a short discussion on how new 3D textiles applications can be developed in close cooperation between the textile industry and the health care sector is presented.
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| 35. |
- Vladescu, Alina, et al.
(author)
-
Influence of the electrolyte’s pH on the properties of electrochemically deposited hydroxyapatite coating on additively manufactured Ti64 alloy
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
-
Journal article (peer-reviewed)abstract
- Properties of the hydroxyapatite obtained by electrochemical assisted deposition (ED) are dependenton several factors including deposition temperature, electrolyte pH and concentrations, appliedpotential. All of these factors directly influence the morphology, stoichiometry, crystallinity,electrochemical behaviour, and particularly the coating thickness. Coating structure together withsurface micro- and nano-scale topography significantly influence early stages of the implant biointegration.The aim of this study is to analyse the effect of pH modification on the morphology,corrosion behaviour and in vitro bioactivity and in vivo biocompatibility of hydroxyapatite preparedby ED on the additively manufactured Ti64 samples. The coatings prepared in the electrolytes withpH = 6 have predominantly needle like morphology with the dimensions in the nanometric scale(~30 nm). Samples coated at pH = 6 demonstrated higher protection efficiency against the corrosiveattack as compared to the ones coated at pH = 5 (~93% against 89%). The in vitro bioactivity resultsindicated that both coatings have a greater capacity of biomineralization, compared to the uncoatedTi64. Somehow, the coating deposited at pH = 6 exhibited good corrosion behaviour and highbiomineralization ability. In vivo subcutaneous implantation of the coated samples into the white rats for up to 21 days with following histological studies showed no serious inflammatory process.
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| 36. |
- Marques, Filipe, et al.
(author)
-
Absorbable cyst brushes
- 2023
-
In: Biomedical microdevices (Print). - : Springer Nature. - 1387-2176 .- 1572-8781. ; 25:3
-
Journal article (peer-reviewed)abstract
- Cytobrushes are used for low-invasive sample collection and screening in multiple diseases, with a significant impact on early detection, prevention, and diagnosis. This study focuses on improving the safety of cell brushing in hard-to-reach locations by exploring brush construction from absorbable materials. We investigated the efficacy of loop brushes made of absorbable suture wires of Chirlac, Chirasorb, Monocryl, PDS II, Vicryl Rapid, Glycolon, and Catgut during their operation in conjunction with fine-needle aspiration in an artificial cyst model. PDS II brushes demonstrated the highest efficiency, while Monocryl and Catgut also provided a significant brushing effect. Efficient brushes portrayed higher flexural rigidity than their counterparts, and their efficiency was inversely proportional to their plastic deformation by the needle. Our results open avenues for safer cell biopsies in hard-to-reach locations by utilizing brushes composed of absorbable materials.
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| 37. |
- Shchukarev, Andrey, et al.
(author)
-
Surface characterization of insulin-coated Ti6Al4V medical implants conditioned in cell culture medium: An XPS study
- 2017
-
In: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 216, s. 33-38
-
Journal article (peer-reviewed)abstract
- © 2017 Elsevier B.V.Surface characterization of insulin-coated Ti6Al4V medical implants, after incubation in α-minimum essential medium (α-MEM), was done by X-ray photoelectron spectroscopy (XPS), in order to analyze the insulin behavior at the implant – α-MEM interface. In the absence of serum proteins in cell culture medium, the coated insulin layer remained intact, but experienced a time-dependent structural transformation exposing hydrophobic parts of the protein toward the solution. The presence of fetal bovine serum (FBS) in the medium resulted in partial substitution of insulin by serum proteins. In spite of some insulin release, the remaining coated layer demonstrated a direct surface effect by stabilizing the structure of protein competitors, and by supporting the accumulation of calcium and phosphate ions at the interface. A structurally stable protein layer with incorporated calcium and phosphate ions at the implant–tissue interface could be an important prerequisite for enhanced bone formation.
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| 38. |
- Leal, José, et al.
(author)
-
Guide to Leveraging Conducting Polymers and Hydrogels for Direct Current Stimulation
- 2023
-
In: Advanced Materials Interfaces. - : John Wiley & Sons. - 2196-7350. ; 10:8
-
Journal article (peer-reviewed)abstract
- The tunable electrical properties of conducting polymers (CPs), their biocompatibility, fabrication versatility, and cost-efficiency make them an ideal coating material for stimulation electrodes in biomedical applications. Several biological processes like wound healing, neuronal regrowth, and cancer metastasis, which rely on constant electric fields, demand electrodes capable of delivering direct current stimulation (DCs) for long times without developing toxic electrochemical reactions. Recently, CPs such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) have demonstrated outstanding capability for delivering DCs without damaging cells in culture while not requiring intermediate buffers, contrary to the current research setups relying on noble-metals and buffering bridges. However, clear understanding of how electrode design and CP synthesis influence DCs properties of these materials has not been provided until now. This study demonstrates that various PEDOT-based CP coatings and hydrogels on rough electrodes can deliver DCs without substantial changes to the electrode and the noticeable development of chemical by-products depending on the electrode area and polymer thickness. A comprehensive analysis of the tested coatings is provided according to the desired application and available resources, alongside a proposed explanation for the observed electrochemical behavior. The CPs tested herein can pave the way toward the widespread implementation of DCs as a therapeutic stimulation paradigm.
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| 39. |
- Jonsson, Amanda, et al.
(author)
-
Therapy using implanted organic bioelectronics
- 2015
-
In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 1:4
-
Journal article (peer-reviewed)abstract
- Many drugs provide their therapeutic action only at specific sites in the body, but are administered in ways that cause the drug’s spread throughout the organism. This can lead to serious side effects. Local delivery from an implanted device may avoid these issues, especially if the delivery rate can be tuned according to the need of the patient. We turned to electronically and ionically conducting polymers to design a device that could be implanted and used for local electrically controlled delivery of therapeutics. The conducting polymers in our device allow electronic pulses to be transduced into biological signals, in the form of ionic and molecular fluxes, which provide a way of interfacing biology with electronics. Devices based on conducting polymers and polyelectrolytes have been demonstrated in controlled substance delivery to neural tissue, biosensing, and neural recording and stimulation. While providing proof of principle of bioelectronic integration, such demonstrations have been performed in vitro or in anesthetized animals. Here, we demonstrate the efficacy of an implantable organic electronic delivery device for the treatment of neuropathic pain in an animal model. Devices were implanted onto the spinal cord of rats, and 2 days after implantation, local delivery of the inhibitory neurotransmitter g-aminobutyric acid (GABA) was initiated. Highly localized delivery resulted in a significant decrease in pain response with low dosage and no observable side effects. This demonstration of organic bioelectronics-based therapy in awake animals illustrates a viable alternative to existing pain treatments, paving the way for future implantable bioelectronic therapeutics. 2015 © The Authors.
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| 40. |
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| 41. |
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| 42. |
- Pirozzi, Ileana, et al.
(author)
-
RVEX : Right Ventricular External Device for Biomimetic Support and Monitoring of the Right Heart
- 2022
-
In: Advanced Materials Technologies. - : Wiley. - 2365-709X. ; 7:8, s. 2101472-2101472
-
Journal article (peer-reviewed)abstract
- Right ventricular (RV) failure remains a significant burden for patients with advanced heart failure, especially after major cardiac surgeries such as implantation of left ventricular assist devices. Device solutions that can assist the complex biological function of heart muscle without the disadvantages of bulky designs and infection-prone drivelines remain an area of pressing clinical need, especially for the right ventricle. In addition, devices that incur contact between blood and artificial surfaces mandate long-term use of blood-thinning medications, carrying increased risks for the patients. This work describes the design of a biomimetic, elastic sleeve to support RV-specific motion via tuned regional mechanical properties. The RV external device (RVEX) in computational models as well as benchtop models and ex vivo (i.e., explanted heart) setups are evaluated to characterize the device and predict functional benefit. Additionally, long-term implantation potential is demonstrated in mice. Finally, the ability to sensorize the RVEX device to yield resistive self-sensing capabilities to continuously monitor ventricular deformation, as demonstrated in benchtop experiments and in live animal surgeries, is proposed.
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| 43. |
- Karlsson, Joakim, 1984-, et al.
(author)
-
Surface oxidation behavior of Ti-6Al-4V manufactured by Electron Beam Melting (EBM®)
- 2015
-
In: Journal of Manufacturing Processes. - : Elsevier BV. - 1526-6125. ; 17, s. 120-126
-
Journal article (peer-reviewed)abstract
- Additive manufacturing is an emerging manufacturing technology that enables production of patient specific implants, today primarily out of titanium. For optimal functionality and proper integration between the titanium implant and the body tissues surface properties, such as surface oxide thickness is of particular importance, as it is primarily the surface of the material which interacts with the body. Hence, in this study the surface oxidation behavior of titanium parts manufactured by Electron Beam Melting (EBM®) is investigated using the surface sensitive techniques ToF-SIMS and AES. Oxide thicknesses comparable to those found on conventionally machined surfaces are found by both analysis techniques. However, a build height dependency is discovered for different locations of the EBM® manufactured parts due to the presence of trapped moisture in the machine and temperature gradients in the build.
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| 44. |
- Alenezi, Ali, et al.
(author)
-
Osseointegration effects of local release of strontium ranelate from implant surfaces in rats
- 2019
-
In: Journal of Materials Science: Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 30:10, s. 116-
-
Journal article (peer-reviewed)abstract
- BACKGROUND : Numerous studies have reported the beneficial effects of strontium on bone growth, particularly by stimulating osteoblast proliferation and differentiation. Thus, strontium release around implants has been suggested as one possible strategy to enhance implant osseointegration. AIM : This study aimed to evaluate whether the local release of strontium ranelate (Sr-ranelate) from implants coated with mesoporous titania could improve bone formation around implants in an animal model. MATERIALS AND METHODS : Mesoporous titania (MT) thin coatings were formed utilizing the evaporation induced self-assembly (EISA) method using Pluronic (P123) with or without the addition of poly propylene glycol (PPG) to create materials with two different pore sizes. The MT was deposited on disks and mini-screws, both made of cp Ti grade IV. Scanning electron microscopy (SEM) was performed to characterize the MT using a Leo Ultra55 FEG instrument (Zeiss, Oberkochen, Germany). The MT was loaded with Sr-ranelate using soaking and the drug uptake and release kinetics to and from the surfaces were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) utilizing a Q-sense E4 instrument. For the in vivo experiment, 24 adult rats were analyzed at two time points of implant healing (2 and 6 weeks). Titanium implants shaped as mini screws were coated with MT films and divided into two groups; supplied with Sr-ranelate (test group) and without Sr-ranelate (control group). Four implants (both test and control) were inserted in the tibia of each rat. The in vivo study was evaluated using histomorphometric analyses of the implant/bone interphase using optical microscopy. RESULTS : SEM images showed the successful formation of evenly distributed MT films covering the entire surface with pore sizes of 6 and 7.2 nm, respectively. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm MT, which was about 3 times more than the observed amount on the 6 nm MT (1200 ng/cm2). Both groups showed sustained release of Sr-ranelate from MT coated disks. The histomorphometric analysis revealed no significant differences in bone implant contact (BIC) and bone area (BA) between the implants with Sr-ranelate and implants in the control groups after 2 and 6 weeks of healing (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks; BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups between 2 and 6 weeks. CONCLUSION : This study could not confirm any positive effects of Sr-ranelate on implant osseointegration.
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| 45. |
- Walladbegi, Java, et al.
(author)
-
Three-dimensional bioprinting using a coaxial needle with viscous inks in bone tissue engineering - An in vitro study
- 2020
-
In: Annals of Maxillofacial Surgery. - : Medknow. - 2249-3816 .- 2231-0746. ; 10:2, s. 370-376
-
Journal article (peer-reviewed)abstract
- Introduction: Vascularized autologous tissue grafts are considered 'gold standard' for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells. Materials and Methods: In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay. Results: Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours. Discussion: Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.
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| 46. |
- Li, Zhen, et al.
(author)
-
Single cell analysis of proliferation and movement of cancer and normal-like cells on nanowire array substrates
- 2018
-
In: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-7518 .- 2050-750X. ; 6:43, s. 7042-7049
-
Journal article (peer-reviewed)abstract
- Nanowires are presently investigated in the context of various biological and medical applications. In general, these studies are population-based, which results in sub-populations being overlooked. Here, we present a single cell analysis of cell cycle and cell movement parameters of cells seeded on nanowires using digital holographic microscopy for time-lapse imaging. MCF10A normal-like human breast epithelial cells and JIMT-1 breast cancer cells were seeded on glass, flat gallium phosphide (GaP), and on vertical GaP nanowire arrays. The cells were monitored individually using digital holographic microscopy for 48 h. The data show that cell division is affected in cells seeded on flat GaP and nanowires compared to glass, with much fewer cells dividing on the former two substrates compared to the latter. However, MCF10 cells that are dividing on glass and flat GaP substrates have similar cell cycle time, suggesting that distinct cell subpopulations are affected differently by the substrates. Altogether, the data highlight the importance of performing single cell analysis to increase our understanding of the versatility of cell behavior on different substrates, which is relevant in the design of nanowire applications.
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| 47. |
- Harris, J. Milton, et al.
(author)
-
Tuning drug release from polyoxazoline-drug conjugates
- 2019
-
In: European Polymer Journal. - : Elsevier BV. - 0014-3057. ; 120
-
Research review (peer-reviewed)abstract
- Poly(2-oxazoline)-drug conjugates with drugs attached via releasable linkages are being developed for drug delivery. Such conjugates with pendent ester linkages that covalently bind drugs to the polymer backbone exhibit significantly slower hydrolytic release rates in plasma than the corresponding PEG- and dextran-drug conjugates. The slow drug release rates in-vitro of these POZ-drug conjugates contribute to extended in-vivo pharmacokinetic profiles. In some instances, the release kinetics may be relatively sustained and ideal for once-a-week subcutaneous injection, whereas the native drug by itself may only have an in-vivo half-life of a few hours. The origin of this unusual kinetic and pharmacokinetic behavior is proposed here to involve folding of the POZ conjugate such that the relatively hydrophobic drug forms a central core, and the relatively hydrophilic polymer wraps around the core and slows enzymatic attack on the drug-polymer chemical linkage. Here we present evidence supporting this hypothesis and demonstrate how the hypothesis can be used to tune hydrolytic release rates and pharmacokinetics. Evidence for the folding hypothesis is taken from hydrolysis kinetics of a range of drugs in plasma, pharmacokinetics of a range of drugs following subcutaneous injection in laboratory animals, and nuclear magnetic resonance (NMR) studies showing folding of the POZ-rotigotine molecule. The drugs included in this study to test the hypothesis are: rotigotine, buprenorphine, dexanabinol, cannabidiol (CBD), Delta(9)-tetrahydrocannabinol (THC) and cannabigerol (CBG).
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| 48. |
- de Oliveira Barud, Hélida Gomes, et al.
(author)
-
Bacterial Nanocellulose in Dentistry: Perspectives and Challenges
- 2021
-
In: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 26:1
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Research review (peer-reviewed)abstract
- Bacterial cellulose (BC) is a natural polymer that has fascinating attributes, such as biocompatibility, low cost, and ease of processing, being considered a very interesting biomaterial due to its options for moldability and combination. Thus, BC-based compounds (for example, BC/collagen, BC/gelatin, BC/fibroin, BC/chitosan, etc.) have improved properties and/or functionality, allowing for various biomedical applications, such as artificial blood vessels and microvessels, artificial skin, and wounds dressing among others. Despite the wide applicability in biomedicine and tissue engineering, there is a lack of updated scientific reports on applications related to dentistry, since BC has great potential for this. It has been used mainly in the regeneration of periodontal tissue, surgical dressings, intraoral wounds, and also in the regeneration of pulp tissue. This review describes the properties and advantages of some BC studies focused on dental and oral applications, including the design of implants, scaffolds, and wound-dressing materials, as well as carriers for drug delivery in dentistry. Aligned to the current trends and biotechnology evolutions, BC-based nanocomposites offer a great field to be explored and other novel features can be expected in relation to oral and bone tissue repair in the near future.
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| 49. |
- Joffre, Thomas, 1987-, et al.
(author)
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Characterization of interfacial stress transfer ability in acetylation-treated wood fibre composites using X-ray microtomography
- 2017
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In: Industrial crops and products (Print). - : Elsevier BV. - 0926-6690 .- 1872-633X. ; 95, s. 43-49
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Journal article (peer-reviewed)abstract
- The properties of the fibre/matrix interface contribute to stiffness, strength and fracture behaviour of fibre-reinforced composites. In cellulosic composites, the limited affinity between the hydrophilic fibres and the hydrophobic thermoplastic matrix remains a challenge, and the reinforcing capability of the fibres is hence not fully utilized. A direct characterisation of the stress transfer ability through pull-out tests on single fibres is extremely cumbersome due to the small dimension of the wood fibres. Here a novel approach is proposed: the length distribution of the fibres sticking out of the matrix at the fracture surface is approximated using X-ray microtomography and is used as an estimate of the adhesion between the fibres and the matrix. When a crack grows in the material, the fibres will either break or be pulled-out of the matrix depending on their adhesion to the matrix: good adhesion between the fibres and the matrix should result in more fibre breakage and less pull-out of the fibres than poor adhesion. The effect of acetylation on the adhesion between the wood fibres and the PLA matrix was evaluated at different moisture contents using the proposed method. By using an acetylation treatment of the fibres it was possible to improve the strength of the composite samples soaked in the water by more than 30%.
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| 50. |
- Lindahl, Carl, et al.
(author)
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Biomimetic calcium phosphate coating of additively manufactured porous CoCr implants
- 2015
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In: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 353, s. 40-47
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Journal article (peer-reviewed)abstract
- The aim of this work was to study the feasibility to use a biomimetic method to prepare biomimetic hydroxyapatite (HA) coatings on CoCr substrates with short soaking times and to characterize the properties of such coatings. A second objective was to investigate if the coatings could be applied to porous CoCr implants manufactured by electron beam melting (EBM). The coating was prepared by immersing the pretreated CoCr substrates and EBM implants into the phosphate-buffered solution with Ca2+ in sealed plastic bottles, kept at 60 degrees C for 3 days. The formed coating was partially crystalline, slightly calcium deficient and composed of plate-like crystallites forming roundish flowers in the size range of 300-500 nm. Cross-section imaging showed a thickness of 300-500 nm. In addition, dissolution tests in Tris-HCl up to 28 days showed that a substantial amount of the coating had dissolved, however, undergoing only minor morphological changes. A uniform coating was formed within the porous network of the additive manufactured implants having similar thickness and morphology as for the flat samples. In conclusion, the present coating procedure allows coatings to be formed on CoCr and could be used for complex shaped, porous implants made by additive manufacturing.
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