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- Gallinetti, Sara, 1985-, et al.
(författare)
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A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement
- 2017
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Ingår i: Journal of The Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 75, s. 495-503
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate cements (CPCs) are extensively used as synthetic bone grafts, but their poor toughness limits their use to non-load-bearing applications. Reinforcement through introduction of fibers and yarns has been evaluated in various studies but always resulted in a decrease in elastic modulus or bending strength when compared to the CPC matrix. The aim of the present work was to improve the interfacial adhesion between fibers and matrix to obtain tougher biocompatible fiber-reinforced calcium phosphate cements (FRCPCs). This was done by adding a polymer solution to the matrix, with chemical affinity to the reinforcing chitosan fibers, namely trimethyl chitosan (TMC). The improved wettability and chemical affinity of the chitosan fibers with the TMC in the liquid phase led to an enhancement of the interfacial adhesion. This resulted in an increase of the work of fracture (several hundred-fold increase), while the elastic modulus and bending strength were maintained similar to the materials without additives. Additionally the TMC-modified CPCs showed suitable biocompatibility with an osteoblastic cell line.
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- Gallinetti, Sara, 1985-, et al.
(författare)
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Titanium reinforced calcium phosphate improves bone formation and osteointegration in ovine calvaria defects : a comparative 52 weeks study
- 2021
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Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- In a 52 week ovine calvaria implantation model, the restoration of cranial defects with a bare titanium mesh (Ti-mesh) and a titanium mesh embedded in a calcium phosphate (CaP-Ti) were evaluated in seven animals. During the study, no major clinical abnormalities were observed, and all sheep presented a normal neurologic assessment. Blood and cerebrospinal fluid analysis, made at termination, did not show any abnormalities. No indentation of the soft tissue was observed for either test article; however, the Ti-mesh burr-hole covers were associated with filling of the calvarial defect by fibrous tissue mainly. Some bone formation was observed at the bottom of the created defect, but no significant bone was formed in the proximity of the implant. The defect sites implanted with CaP-Ti were characterized by a moderate degradation of the calcium phosphate (CaP) that was replaced by mature bone tissue. Calcium-phosphate-filled macrophages were observed in all animals, indicating that they might play a vital role in osteogenesis. The newly formed bone was present, especially at the bony edges of the defect and on the dura side. Integration of the Ti-mesh in a CaP improved bone formation and osteointegration in comparison to a bare Ti-mesh.
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| 14. |
- Gasser, T. Christian, et al.
(författare)
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Collagen fiber orientation in Abdominal Aortic Aneurysms wall
- 2010
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Konferensbidrag (refereegranskat)abstract
- Introduction Collagen is the most abundant protein in mammals and gives mechanical strength, stiffness and toughness to biological tissues like skin, tendon, bone, and vasculature [1]. Collagen fibrils of about 0.1 micrometers in diameters are the basic building blocks of fibrous collagenous tissues and their organization into suprafibrilar structures determines the tissue’s macroscopic mechanical properties. For example, detailed data regarding the organization of strong bundles of collagen might be critical to predict the onset of tissue failure, as it is clinically motivated by a rupture risk assessment of Abdominal Aortic Aneurysm (AAA). Previously proposed structural constitutive models for soft biological tissues [2, 3] integrated information regarding the collagen orientation, and regardless of their popularity, the requested microstructural information is not yet available in the open literature. Method and Materials The present study investigated the collagen formation in 12 AAA wall specimens stemming from 9 patients and harvested during elective aneurysm repair at Karolinska University Hospital, Stockholm, Sweden. Specimens of about 1.0 x 1.0 centimeter were squeezed between Plexiglas plates and fixated in formaldehyde for 24 hours. Fixated specimens were dehydrated and embedded in paraffin (Tissue Tek VIP 3000, Sakura)and sliced at a thickness of 7.0 micrometers (HM 360, Microm). To reinforce the birefringend properties of collagen the slices were stained with Picrus Sirius red before three-dimensional collagen fiber orientations were identified in a polarized light microscope (BX 50, Olympus) equipped with an Universal Rotary Stage (Zeiss). Specifically, the collagen orientations were measured at 36 points at each slice, where three slices across the thickness of the AAA wall were considered. The derived structural information was included in two different structural constitutive models and reported macroscopic mechanical data [4] was used to estimate mechanical parameters of the constitutive formulations. Results and Conclusions Collagen fiber orientation in the AAA wall is considerably spread out and no difference amongst medial and adventitial layers could be identified; a result in line with the layered structure of, e.g., cerebral aneurysms [5] but in clear contrast to the structural differences amongst the layers of normal arteries [6]. Collagen fibers in the AAA wall are predominantly aligned in circumferential direction, which might explain its higher stiffness along that direction [4]. Naturally, the complex collagen formation cannot be captured by a single (or two) families of collagen fibers and associated constitutive models are not applicable. Collagen turnover is thought to be mediated by the local stress or strain state [7] and the supra-physiological stresses in the AAA wall might cause the identified pathological collagen orientation. References [1] P. Fratzl, editor. Springer-Verlag, New York, 2008. [2] T. C. Gasser, et. al. J. R. Soc. Interface, 3:15–35, 2006. [3] S. Federico and T. C. Gasser. J. R.Soc. Interface, 2009. [4] J. P. Vande Geest et al.. J Biomech. 39, 1324--1334, 2006. [5] P. B. Canham, et al.. Neurological Res., 21, 618--626, 1999. [6] P. B. Canham, et al. Cardiovasc. Res. 23, 973-982, 1989. [7] J. D. Humphrey, Springer-Verlag, New York, 2002.
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| 15. |
- Gasser, T. Christian, et al.
(författare)
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Spatial orientation of collagen fibers in the abdominal aortic aneurysm's wall and its relation to wall mechanics
- 2012
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 8:8, s. 3091-3103
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Tidskriftsartikel (refereegranskat)abstract
- Collagen is the most abundant protein in mammals and provides the abdominal aortic aneurysm (AAA) wall with mechanical strength, stiffness and toughness. Specifically, the spatial orientation of collagen fibers in the wall has a major impact on its mechanical properties. Apart from valuable microhistological information, this data can be integrated by histomechanical constitutive models thought to improve biomechanical simulations, i.e. to improve the biomechanical rupture risk assessment of AAAs. Tissue samples (n = 24) from the AAA wall were harvested during elective AAA repair, fixated, embedded, sectioned and investigated by polarized light microscopy. The birefringent properties of collagen were reinforced by picrosirius red staining and the three-dimensional collagen fiber orientations were identified with a universal rotary stage. Two constitutive models for collagen fibers were used to integrate the identified structural information in a macroscopic AAA wall model. The collagen fiber orientation in the AM wall was widely dispersed and could be captured by a Bingham distribution function (kappa(1) = 11.6, kappa(2) = 9.7). The dispersion was much larger in the tangential plane than in the cross-sectional plane, and no significant difference between the medial and adventitial layers could be identified. The layered directional organization of collagen in normal aortas was not evident in the AAA. The collagen organization identified, combined with constitutive descriptions of collagen fibers that depend on its orientation, explain the anisotropic (orthotropic) mechanical properties of the AAA wall. The mechanical properties of collagen fibers depend largely on their undulation, which is an important structural parameter that requires further experimental investigation.
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| 16. |
- Hulsart-Billstrom, Gry, 1982-, et al.
(författare)
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Guiding bone formation using semi‐onlay calcium phosphate implants in an ovine calvarial model
- 2022
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 16:5, s. 435-447
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Tidskriftsartikel (refereegranskat)abstract
- The restoration of cranio-maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof-of-concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium-reinforced porous calcium phosphate (CaP) implants (n = 12) over the frontal bone in a sheep model (n = 6). The animals were euthanized after week 13 and the specimens were subject to micro-computed tomography (μCT) and comprehensive histological analysis. Histology showed that the space between implant and the recipient bone was filled with a higher percentage of newly formed bone (NFB) versus soft tissue with a median of 53% and 47%, respectively. Similar results were obtained from the μ-CT analysis, with a median of 56% NFB and 44% soft tissue filling the void. Noteworthy, significantly higher bone-implant contact was found for the CaP (78%, range 14%–94%) versus the Titanium (29%, range 0%–75%) portion of the implant exposed to the surrounding bone. The histological analysis indicates that the CaP replacement by bone is driven by macrophages over time, emphasized by material-filled macrophages found in close vicinity to the CaP with only a small number of single osteoclasts found actively remodeling the NFB. This study shows that CaP based implants can be assembled with the help of additive manufacturing to guide vertical bone formation without decortification or administration of growth factors. Furthermore, it highlights the potential disadvantage of a seamless fit between the implant and the recipient's bone.
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- Lewin, Susanne, et al.
(författare)
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Monetite-based composite cranial implants demonstrate long-term clinical volumetric balance by concomitant bone formation and degradation
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 128, s. 502-513
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Tidskriftsartikel (refereegranskat)abstract
- The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation. In this study, the volumetric change at the implant site was quantified longitudinally by clinical computed tomography (CT). The retrospective CT datasets had been acquired postoperatively ( n = 10), in 1-year ( n = 9) and 3-year ( n = 5) follow-ups. In the 1-year follow-up, the total volumetric change at the implant site was-8 +/- 8%. A volumetric increase (bone formation) was found in the implant-bone interface, and a volumetric decrease was observed in the central region (CaP degradation). In the subjects with 2-or 3-year follow-ups, the rate of volumetric decrease slowed down or plateaued. The reported degradation rate is lower than previous clinical studies on monetite, likely due to the presence of pyrophosphate in the monetite-based CaP-formulation. A 31-months retrieval specimen analysis demonstrated that parts of the CaP had been remodeled into bone. The CaP phase composition remained stable, with 6% transformation into hydroxyapatite. In conclusion, this study demonstrates successful bone-bonding between the CaP-material and the recipient bone, as well as a long-term volumetric balance in cranial defects repaired with the monetitebased composite implant, which motivates further clinical use. The developed methods could be used in future studies for correlating spatiotemporal information regarding bone regeneration and CaP degradation to e.g. patient demographics. Statement of significance In bone defect reconstructions, the use of calcium phosphate (CaP) bioceramics ideally results in a volumetric balance between bone formation and CaP degradation. Clinical data on the volumetric balance is nevertheless lacking, especially for monetite-based CaPs. Here, this concept is investigated for a composite cranial implant. The implant volumes were quantified from clinical CT-data: postoperatively, one year and three years postoperatively. In total,-8 +/- 8% ( n = 9) volumetric change was observed after one year. But the change plateaued, with only 2% additional decrease at the 3-year follow-up ( n = 5), indicating a lower CaP degradation rate. Osseointegration was seen at the bone-implant interface, with a 9 +/- 7% volumetric change after one year. This study presented the first quantitative spatiotemporal CT analysis of monetite-based CaPs.
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- Lopes, Viviana, et al.
(författare)
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Human Whole Blood Interactions with Craniomaxillofacial Reconstruction Materials : Exploring In Vitro the Role of Blood Cascades and Leukocytes in Early Healing Events
- 2023
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Ingår i: Journal of Functional Biomaterials. - : MDPI AG. - 2079-4983. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated early interactions between three alloplastic materials (calcium phosphate (CaP), titanium alloy (Ti), and polyetheretherketone (PEEK) with human whole blood using an established in vitro slide chamber model. After 60 min of contact with blood, coagulation (thrombin-antithrombin complexes, TAT) was initiated on all test materials (Ti > PEEK > CaP), with a significant increase only for Ti. All materials showed increased contact activation, with the KK-AT complex significantly increasing for CaP (p < 0.001), Ti (p < 0.01), and PEEK (p < 0.01) while only CaP demonstrated a notable rise in KK-C1INH production (p < 0.01). The complement system had significant activation across all materials, with CaP (p < 0.0001, p < 0.0001) generating the most pronounced levels of C3a and sC5b-9, followed by Ti (p < 0.001, p < 0.001) and lastly, PEEK (p < 0.001, p < 0.01). This activation correlated with leukocyte stimulation, particularly myeloperoxidase release. Consequently, the complement system may assume a more significant role in the early stages post implantation in response to CaP materials than previously recognized. Activation of the complement system and the inevitable activation of leukocytes might provide a more favorable environment for tissue remodeling and repair than has been traditionally acknowledged. While these findings are limited to the early blood response, complement and leukocyte activation suggest improved healing outcomes, which may impact long-term clinical outcomes.
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| 22. |
- Malmberg, Per, 1974, et al.
(författare)
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Targeted ToF-SIMS Analysis of Macrophage Content from a Human Cranial Triphasic Calcium Phosphate Implant
- 2021
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 4:9, s. 6791-6798
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play a key role in determining the fate of implanted biomaterials, especially for biomaterials such as calcium phosphates (CaPs) where these cells play a vital role in material resorption and osteogenesis, as shown in different models, including clinical samples. Although substantial consideration is given to the design and validation of different CaPs, relatively little is known about their material-cell interaction. Specifically, the intracellular content of different CaP phases remains to be assessed, even though CaP-filled macrophages have been observed in several studies. In this study, 2D/3D ToF-SIMS imaging and multivariate analysis were directly applied on the histology samples of an explant to reveal the content of macrophages. The cellular content of the macrophages was analyzed to distinguish three CaP phases, monetite, beta-tricalcium phosphate, and pyrophosphate, which are all part of the monetite-based CaP implant composition under study. ToF-SIMS combined with histology revealed that the content of the identified macrophages was most similar to that of the pyrophosphate phase. This study is the first to uncover distinct CaP phases in macrophages from a human multiphasic CaP explant by targeted direct cell content analysis. The uncovering of pyrophosphate as the main phase found inside the macrophages is of great importance to understand the impact of the selected material in the process of biomaterial-instructed osteogenesis.
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| 23. |
- Sundblom, Jimmy, 1981-, et al.
(författare)
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Gentamicin loading of calcium phosphate implants : implications for cranioplasty
- 2019
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Ingår i: Acta Neurochirurgica. - : SPRINGER WIEN. - 0001-6268 .- 0942-0940. ; 161:6, s. 1255-1259
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurgical site infections (SSI) are a significant risk in cranioplasty, with reported rates of around 8-9%. The most common bacteria associated with these nosocomial infections are of the Staphylococcus species, which have the ability to form biofilm. The possibility to deliver antibiotics, such as gentamicin, locally rather than systemically could potentially lower the early postoperative SSI. Various antibiotic dosages are being applied clinically, without any true consensus on the effectiveness.MethodsDrug release from calcium phosphate (CaP), polyetheretherketone (PEEK), and titanium (Ti) samples was evaluated. Microbiological studies with Staphylococcus aureus (SA) and Staphylococcus epidermidis (SE) including strains from clinical infection were used to establish clinically relevant concentrations.ResultsThe CaP samples were able to retain and release gentamicin overtime, whereas the Ti and PEEK samples did not show any drug uptake or release. A gentamicin loading concentration of 400g/ml was shown to be effective in in vitro microbiological studies with both SA and SE.ConclusionsOut of the three materials studied, only CaP could be loaded with gentamicin. An initial loading concentration of 400g/ml appears to establish an effective gentamicin concentration, possibly translating into a clinical benefit in cranioplasty.
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