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Larsson, Sune
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Publications (10 of 106) Show all publications
Procter, P., Pujari-Palmer, M., Hulsart Billström, G., Insley, G., Larsson, S. & Engqvist, H. (2018). A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue. In: : . Paper presented at 34th Annual Meeting of Orthopaedic Trauma association, October 17 – 20, 2018, Kissimmee (Orlando), FL, USA.
Open this publication in new window or tab >>A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue
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2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Keywords
Tissue adhesive, biomaterial, calcium phosphate
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-366372 (URN)
Conference
34th Annual Meeting of Orthopaedic Trauma association, October 17 – 20, 2018, Kissimmee (Orlando), FL, USA
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-03-06Bibliographically approved
Larsson, S. (2018). Clavicula fractures: considerations when plating. Injury, 49(suppl. 1), S24-S28
Open this publication in new window or tab >>Clavicula fractures: considerations when plating
2018 (English)In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 49, no suppl. 1, p. S24-S28Article in journal (Refereed) Published
Abstract [en]

The preferred treatment of clavicula midshaft fractures in adults has gone from being very conservative into surgery being frequently recommended. However, based on recent meta-analysis favorable outcome with internal fixation is not as consistent as previously reported. Probably due to a combination of indications for surgery becoming too wide and surgery being performed by a wider group of surgeons. When using plating for clavicula fractures there are several considerations to consider to improve outcome while reducing the risk for complications. Traditionally a horizontal approach along the clavicula is used as it provides good exposure. However, this incision is associated with a high risk for permanent anterior chest wall numbness that might be very disturbing for patients. A vertical incision can instead be used. Plates are traditionally placed in a superior position. An alternative can be an anterior-inferior position that allows better soft tissue coverage, less risk for hardware protrusion, longer screws can be used and the risk for damaging the underlying neurovascular bundle is reduced. Angle-stable screw-plate systems has not in a convincing way shown any benefit in clavicula fractures. In part because most patients have good bone quality where conventional screws will be sufficient.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Clavicula fractures, Internal fixation, Plate fixation, Complications, Adults
National Category
Orthopaedics Surgery
Identifiers
urn:nbn:se:uu:diva-360547 (URN)10.1016/S0020-1383(18)30298-5 (DOI)000437774800006 ()29929688 (PubMedID)
Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2018-09-20Bibliographically approved
Christersson, A., Larsson, S. & Sandén, B. (2018). Clinical outcome after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: A prospective randomized study. Scandinavian Journal of Surgery, 107(1), 82-90
Open this publication in new window or tab >>Clinical outcome after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: A prospective randomized study
2018 (English)In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 107, no 1, p. 82-90Article in journal (Refereed) Published
Abstract [en]

Introduction: this study aimed to evaluate clinical results after plaster cast fixation for 10 days versus 1 month of moderately displaced and reduced distal radius fractures.Material and Methods: in a prospective randomized study, 109 patients with moderately displaced and conservatively treated distal radius fractures (age ≥50 years) were randomized 10 days after reduction to either removal of the plaster cast and immediate mobilization (active group) or to continued plaster cast fixation for another 3 weeks (control group). Grip strength, pincer strength, range of motion, and pain were assessed at 1, 4, and 12 months after reduction. Clinical outcome was evaluated using three functional assessment scores at 12 months.Results: treatment failed in 3/54 (6%) patients in the active group. one of these patients had the plaster cast reinstituted because of feelings of instability. the fractures in the other two patients displaced severely after mobilization and were therefore treated surgically. for the remaining 51 patients in the active group, the range of wrist motion was slightly better at 1 month compared with the controls, but there were no differences in grip or pincer strength or pain at the 1-month follow-up. there were no differences between the active and control group in any outcome at 4 or 12 months, including functional assessment scores at 12 months.Conclusion: treatment with mobilization 10 days after reduction of moderately displaced distal radius fractures resulted in a few treatment failures compared with none among controls. the only functional benefit for the remaining patients was a small and transient increase in range of motion at the 1-month follow-up. plaster cast removal 10 days after reduction in moderately displaced distal radius fractures is therefore not recommended.

National Category
Orthopaedics Surgery
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-334618 (URN)10.1177/1457496917731184 (DOI)000429935400013 ()
Available from: 2017-11-24 Created: 2017-11-24 Last updated: 2018-07-18Bibliographically approved
Procter, P., Pujari-Palmer, M., Hulsart Billström, G., Larsson, S., Insley, G. & Engqvist, H. (2018). Designing A Commercial Biomaterial For A Specific Unmet Clinical Need –: An Adhesive Odyssey. In: : . Paper presented at 26th EORS Annual Meeting 25th – 28th September 2018, Galway, Ireland.
Open this publication in new window or tab >>Designing A Commercial Biomaterial For A Specific Unmet Clinical Need –: An Adhesive Odyssey
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2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

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.

Keywords
Tissue adhesive, biomaterial, calcium phosphate
National Category
Medical Materials Composite Science and Engineering Ceramics Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-366369 (URN)
Conference
26th EORS Annual Meeting 25th – 28th September 2018, Galway, Ireland
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2019-03-06Bibliographically approved
Lindahl, K., Astrom, E., Dragomir, A., Symoens, S., Coucke, P., Larsson, S., . . . Kindmark, A. (2018). Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy. Bone, 114, 268-277
Open this publication in new window or tab >>Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
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2018 (English)In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 114, p. 268-277Article in journal (Refereed) Published
Abstract [en]

Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.

Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.

Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.

Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.

Keywords
Osteogenesis imperfecta, Recessive, Collagen type 1, Glycosaminoglycan, OASIS, CREB3L1
National Category
Orthopaedics Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-362634 (URN)10.1016/j.bone.2018.06.019 (DOI)000441369000029 ()29936144 (PubMedID)
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2019-04-02Bibliographically approved
Mei, X., Atturo, F., Wadin, K., Larsson, S., Agrawal, S., Ladak, H. M., . . . Rask-Andersen, H. (2018). Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration. Upsala Journal of Medical Sciences, 123(3), 131-142
Open this publication in new window or tab >>Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration
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2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 131-142Article in journal (Refereed) Published
Abstract [en]

Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.

Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.

Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.

Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Human, micro-computerized tomography, synchrotron phase contrast imaging, temporal bone, Uppsala collection
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-368772 (URN)10.1080/03009734.2018.1492654 (DOI)000446977000001 ()30204028 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Hulsart Billström, G., Selvaraju, R., Estrada, S., Lubberink, M., Asplund, V., Bergman, K., . . . Antoni, G. (2018). Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept. Journal of Controlled Release, 285, 178-186
Open this publication in new window or tab >>Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept
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2018 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, p. 178-186Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

Keywords
Bone morphogenetic protein 2, Bone tissue engineering, Hydrogel, Micro computed tomography, Positron emission tomography, Single-photon emission computed tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356465 (URN)10.1016/j.jconrel.2018.07.012 (DOI)000441737400015 ()30005906 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 262948
Note

G. Hulsart-Billström and R. K. Selvaraju contributed equally to this work and should be regarded as joint first authors.

Available from: 2018-07-28 Created: 2018-07-28 Last updated: 2018-10-10Bibliographically approved
Augat, P. & Larsson, S. (2018). Plating of fractures: current treatments and complications. Injury, 49, S1-S1
Open this publication in new window or tab >>Plating of fractures: current treatments and complications
2018 (English)In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 49, p. S1-S1Article in journal, Editorial material (Other academic) Published
National Category
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-365269 (URN)10.1016/S0020-1383(18)30293-6 (DOI)000437774800001 ()29929683 (PubMedID)
Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2018-11-19Bibliographically approved
Christersson, A., Larsson, S. & Sörensen, J. (2018). Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT.. EJNMMI Research, 8, Article ID 65.
Open this publication in new window or tab >>Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT.
2018 (English)In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 8, article id 65Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Localizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent. Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6-8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.

RESULTS: A likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.

CONCLUSIONS: Dual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.

Keywords
Chronic osteomyelitis, FDG-PET/CT, NaF-PET/CT, Preoperative planning, Surgical treatment
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-357426 (URN)10.1186/s13550-018-0426-0 (DOI)000439318100002 ()30032355 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-10-03Bibliographically approved
Yan, H., Casalini, T., Hulsart Billström, G., Wang, S., Oommen, O. P., Salvalaglio, M., . . . Varghese, O. P. (2018). Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. Biomaterials, 161, 190-202
Open this publication in new window or tab >>Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
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2018 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 161, p. 190-202Article in journal (Refereed) Published
Abstract [en]

Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.

National Category
Polymer Chemistry
Identifiers
urn:nbn:se:uu:diva-343820 (URN)10.1016/j.biomaterials.2018.01.041 (DOI)000427100300017 ()29421555 (PubMedID)
Funder
Swedish Foundation for Strategic Research , 139400126, 139400127EU, FP7, Seventh Framework Programme, NMP3-LA-2011-262948
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-03-01 Created: 2018-03-01 Last updated: 2018-05-16Bibliographically approved
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