| 1. |
- Omar, Omar, et al.
(författare)
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In situ bone regeneration of large cranial defects using synthetic ceramic implants with a tailored composition and design
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:43, s. 26660-26671
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Tidskriftsartikel (refereegranskat)abstract
- The repair of large cranial defects with bone is a major clinical challenge that necessitates novel materials and engineering solutions. Three-dimensionally (3D) printed bioceramic (BioCer) implants consisting of additively manufactured titanium frames enveloped with CaP BioCer or titanium control implants with similar designs were implanted in the ovine skull and at s.c. sites and retrieved after 12 and 3 mo, respectively. Samples were collected for morphological, ultrastructural, and compositional analyses using histology, electron microscopy, and Raman spectroscopy. Here, we show that BioCer implants provide osteoinductive and microarchitectural cues that promote in situ bone regeneration at locations distant from existing host bone, whereas bone regeneration with inert titanium implants was confined to ingrowth from the defect boundaries. The BioCer implant promoted bone regeneration at nonosseous sites, and bone bonding to the implant was demonstrated at the ultrastructural level. BioCer transformed to carbonated apatite in vivo, and the regenerated bone displayed a molecular composition indistinguishable from that of native bone. Proof-of-principle that this approach may represent a shift from mere reconstruction to in situ regeneration was provided by a retrieved human specimen, showing that the BioCer was transformed into well-vascularized osteonal bone, with a morphology, ultrastructure, and composition similar to those of native human skull bone.
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| 2. |
- Procter, Philip, et al.
(författare)
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Designing A Commercial Biomaterial For A Specific Unmet Clinical Need – : An Adhesive Odyssey
- 2018
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Konferensbidrag (refereegranskat)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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| 3. |
- Pujari-Palmer, Michael, et al.
(författare)
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A Novel Class of Injectable Bioceramics That Glue Tissues and Biomaterials
- 2018
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 11:12
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Skjöldebrand, Charlotte, et al.
(författare)
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Si-Fe-C-N Coatings for Biomedical Applications : A Combinatorial Approach
- 2020
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Ingår i: Materials. - : MDPI. - 1996-1944 .- 1996-1944. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Ceramic coatings may prolong the lifetime of joint implants. Certain ions and wear debris may however lead to negative biological effects. SiN-based materials may substantially reduce these effects, but still need optimization for the application. In this study, a combinatorial deposition method enabled an efficient evaluation of a range of Si-Fe-C-N coating compositions on the same sample. The results revealed compositional gradients of Si (26.0-33.9 at.%), Fe (9.6-20.9 at.%), C (8.2-13.9 at.%) and N (39.7-47.2 at.%), and low oxygen contaminations (0.3-0.6 at.%). The mechanical properties varied with a hardness (H) ranging between 13.7-17.3 GPa and an indentation modulus (M) between 190-212 GPa. Both H and M correlated with the Si (H and M increased as Si increased) and Fe (H and M decreased as Fe increased) content. A slightly columnar morphology was observed in cross-sections, as well as a surface roughness in the nm range. A cell study revealed adhering pre-osteogenic MC3T3 cells, with a morphology similar to that of cells seeded on a tissue culture plastic control. The investigated coatings could be considered for further investigation due to the ability to tune their mechanical properties while maintaining a smooth surface, together with their promising in vitro cell response.
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| 5. |
- Katsaros, Ioannis, et al.
(författare)
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Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties
- 2022
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Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983 .- 2079-4983. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si3N4 surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si3N4 implants while maintaining the bacteriostatic properties.
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| 6. |
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| 7. |
- Ghajeri, Farnaz, et al.
(författare)
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The Influence of Residuals Combining Temperature and Reaction Time on Calcium Phosphate Transformation in a Precipitation Process
- 2022
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Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983 .- 2079-4983. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Precipitation is one of the most common processes to synthesize hydroxyapatite, which is the human body’s mineral forming bone and teeth, and the golden bioceramic material for bone repair. Generally, the washing step is important in the precipitation method to remove the residuals in solution and to stabilize the phase transformation. However, the influence of residuals in combination with the reaction temperature and time, on calcium phosphate formation, is not well studied. This could help us with a better understanding of the typical synthesis process. We used a fixed starting ion concentration and pH in our study and did not adjust it during the reaction. XRD, FTIR, ICP-OES, and SEM have been used to analyze the samples. The results showed that combining residuals with both reaction temperature and time can significantly influence calcium phosphate formation and transformation. Dicalcium phosphate dihydrate formation and transformation are sensitive to temperature. Increasing temperature (60◦C) can inhibit the formation of acidic calcium phosphate or transform it to other phases, and further the particle size. It was also observed that high reaction temperature (60◦C) results in higher precipitation efficiency than room temperature. A low ion concentration combining reaction temperature and time could still significantly influence the calcium phosphate transformation during the drying. © 2022 by the authors.
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| 8. |
- Persson, Johan, et al.
(författare)
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Stiffness and strength of cranioplastic implant systems in comparison to cranial bone
- 2018
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 46:3, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to evaluate skull replacement options after decompressive craniectomy by systematically investigating which combination of geometrical properties and material selection would result in a mechanical response comparable in stiffness to that of native skull bone and a strength as high or higher than the same. Materials and methods: The study was conducted using a Finite Element Model of the top part of a human skull. Native skull bone, autografts and commercial implants made of PEEK, solid titanium, two titanium meshes and a titanium-ceramic composite were modeled under a set load to evaluate deformation and maximum stress. Results: The computational result showed a large variation of the strength and effective stiffness of the autografts and implants. The stiffness of native bone varied by a factor of 20 and the strength by a factor of eight. The implants span the entire span of the native skull, both in stiffness and strength. Conclusion: All the investigated implant materials had a potential for having the same effective stiffness as the native skull bone. All the materials also had the potential to be as strong as the native bone. To match inherent properties, the best choice of material and thickness is thus patient specific, depending on the quality of the patient's native bone.
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| 9. |
- Pujari-Palmer, Michael, et al.
(författare)
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Influence of cement compressive strength and porosity on augmentation performance in a model of orthopedic screw pull-out
- 2018
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier. - 1751-6161 .- 1878-0180. ; 77, s. 624-633
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Tidskriftsartikel (refereegranskat)abstract
- Disease and injuries that affect the skeletal system may require surgical intervention and internal fixation, i.e. orthopedic plate and screw insertion, to stabilize the injury and facilitate tissue repair. If the surrounding bone quality is poor the screws may migrate, or the bone may fail, resulting in screw pull-out. Though numerous studies have shown that cement augmentation of the interface between bone and implant can increase screw holding strength in bone, the physical properties of cement that influence pull-out force have not been investigated. The present study sought to determine how the physical properties of calcium phosphate cements (CPCs), and the strength of the biological or synthetic material surrounding the augmented screw, affected the corresponding orthopedic screw pull-out force in urethane foam models of healthy and osteoporotic bone (Sawbones). In the simplest model, where only the bond strength between screw thread and cement (without Sawbone) was tested, the correlation between pull-out force and cement compressive strength (R2 = 0.79) was weaker than correlation with total cement porosity (R2 = 0.89). In open pore Sawbone that mimics “healthy” cancellous bone density the stronger cements produced higher pull-out force (50-60% increase). Higher strength, lower porosity, cements also produced higher pull-out forces (50-190% increase) in Sawbones with cortical fixation if the failure strength of the cortical material was similar to (bovine tibial bone), or greater than (metal shell), actual cortical bone. This result is of particular clinical relevance where fixation with a metal plate implant is indicated, as the nearby metal can simulate a thicker cortical shell and, thereby, increase the pull-out force of screws augmented with stronger cements. The improvement in pull-out force was apparent even at low augmentation volumes of 0.5 ml (50% increase), which suggest that in clinical situations where augmentation volume is limited the stronger, lower porosity CPCs may still produce a significant improvement in screw holding strength. When correlations of all the tested models were compared both cement porosity and compressive strength accurately predicted pull-out force (R2=1.00, R2=0.808), though prediction accuracy depended upon the strength of the material surrounding the Sawbone. The correlations strength was low for bone with no, or weak, cortical fixation. Higher strength and lower porosity CPCs also produced greater pull-out force (1-1.5 kN) than commercial CPC (0.2-0.5kN), but lower pull-out force than PMMA (2-3 kN). The results of this study suggest that the likelihood of screw fixation failure may be reduced by selecting calcium phosphate cements with lower porosity and higher bulk strength, in patients with healthy bone mineral density and/or sufficient cortical thickness. This is of particular clinical relevance when fixation with metal plates is indicated, or where the augmentation volume is limited.
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| 10. |
- Skjöldebrand, Charlotte, 1989-, et al.
(författare)
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Biocompatibility of co-sputtered Si-Fe-C-N coatings
- 2018
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION: Hip joint arthroplasty is a common and increasingly frequent procedure that can relieve pain and restore mobility for individuals with e.g. severe osteoarthritis. While the procedure is common and to a large extent considered successful there is a need to prolong the lifespan of the implants to meet the need of a more active patient group, living longer. One of the main limiting factors behind the implant lifetime is the generation of particulate and ionic wear debris that causes an activation of the immune system. This debris originates in the articulating surfaces and one attempt to minimize the generation of debris is to deposit a ceramic coating on metal implant parts. The hard ceramic coatings, such as silicon nitride, could improve the wear resistance as well as act as a barrier for metal ion release.1,2 The silicon nitride coatings in this study were co-deposited with Fe and C in order to increase the deposition rate and tune the dissolution rate.METHODS: The coatings were deposited using reactive magnetron sputtering onto silicon wafer substrates. The Si target (99.99% purity) was powered with pulsed DC at 200 W, 200 kHz and 2 µs. The Fe target (99.99% purity) and C target (99.99% purity) were powered by DC aggregates at 25 W and 65 W respectively. The targets were positioned at an angle (38.81˚) and no rotation was used during deposition. Nitrogen was introduced as a reactive gas in addition to the inert Ar at a ratio of 0.3. The deposition time was 10 000 s.Based on the intended compositional gradients five points (4 corners in a square spaced 40 mm apart and the middle) on the sample were selected. No two points on the sample are identical and could be treated like individual samples.The composition was determined using ERDA and the surface properties were estimated with atomic force microscopy (AFM) in non-contact mode.The biocompatibility was assessed in vitro with osteo-progenitor cells from mouse (MC3T3)..RESULTS: The ERDA investigation revealed clear compositional gradients. The Si content ranged from 26 at.% in point 4 to 34 at.% in point 1. The Fe content changed in a complementary manner with a maximum of 20 at.% in point 4 and a minimum of 10 at.% in point 1. The carbon content ranged from 8 at.% in point 1 to 14 in point 4. In addition to the expected gradients the N content ranged from 40 at.% to 47 at.%.Despite the differences in composition the surface appearance and roughness remained similar for all the points (1-5) (Figure 1).The cell study showed surviving cells that adhered to the Si-N-Fe-C surface for all five points.DISCUSSION & CONCLUSIONS: Co-sputtering yielded compositional gradients along the silicon wafer. The unexpected gradient of N-content – N was present as a gas - is likely due to the ability of Si to form nitrides as seen from the low enthalpy of formation for Si3N4 (-743 kJ/mol). The low surface roughness is likely a consequence of the smooth Si-wafer substrate, it is however reasonable to assume that a polished metal substrate would also yield low surface roughness. The adhesion of the cells indicates biocompatibility. In summary the low surface roughness combined with the biocompatibility make the coatings interesting for further investigations. REFERENCES1. Pettersson, M. et al. (2016) Mater. Sci. Eng. C. Mater. Biol. Appl. 62, 497–505 .2. Pettersson, M. et al. (2013) J. Mech. Behav. Biomed. Mater. 25, 41–7. ACKNOWLEDGEMENTS: The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under the LifeLongJoints Project, Grant Agreement no. GA-310477.
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