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Pujari-Palmer, Michael
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Publications (10 of 18) Show all publications
Liu, X., Pujari-Palmer, M., Wenner, D., Procter, P., Insley, G. & Engqvist, H. (2019). Adhesive Cements That Bond Soft Tissue Ex Vivo. Materials, 12(15), Article ID 2473.
Open this publication in new window or tab >>Adhesive Cements That Bond Soft Tissue Ex Vivo
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2019 (English)In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 15, article id 2473Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to evaluate the soft tissue bond strength of a newly developed, monomeric, biomimetic, tissue adhesive called phosphoserine modified cement (PMC). Two types of PMCs were evaluated using lap shear strength (LSS) testing, on porcine skin: a calcium metasilicate (CS1), and alpha tricalcium phosphate (alpha TCP) PMC. CS1 PCM bonded strongly to skin, reaching a peak LSS of 84, 132, and 154 KPa after curing for 0.5, 1.5, and 4 h, respectively. Cyanoacrylate and fibrin glues reached an LSS of 207 kPa and 33 kPa, respectively. alpha TCP PMCs reached a final LSS of approximate to 110 kPa. In soft tissues, stronger bond strengths were obtained with alpha TCP PMCs containing large amounts of amino acid (70-90 mol%), in contrast to prior studies in calcified tissues (30-50 mol%). When alpha TCP particle size was reduced by wet milling, and for CS1 PMCs, the strongest bonding was obtained with mole ratios of 30-50% phosphoserine. While PM-CPCs behave like stiff ceramics after setting, they bond to soft tissues, and warrant further investigation as tissue adhesives, particularly at the interface between hard and soft tissues.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
tissue adhesive, phosphoserine, phosphoserine modified cement, biomaterial, bioceramic, lap shear, bone cement, silicate, calcium phosphate, self-setting
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-393904 (URN)10.3390/ma12152473 (DOI)000482576900134 ()31382566 (PubMedID)
Funder
Swedish Research Council, RMA15-0110
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2019-10-18 Created: 2019-10-18 Last updated: 2019-10-18Bibliographically approved
Yu, Y., Guo, H., Pujari-Palmer, M., Stevensson, B., Grins, J., Engqvist, H. & Eden, M. (2019). Advanced solid-state H-1/P-31 NMR characterization of pyrophosphate-doped calcium phosphate cements for biomedical applications: The structural role of pyrophosphate. Ceramics International, 45(16), 20642-20655
Open this publication in new window or tab >>Advanced solid-state H-1/P-31 NMR characterization of pyrophosphate-doped calcium phosphate cements for biomedical applications: The structural role of pyrophosphate
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2019 (English)In: Ceramics International, ISSN 0272-8842, E-ISSN 1873-3956, Vol. 45, no 16, p. 20642-20655Article in journal (Refereed) Published
Abstract [en]

From a suite of advanced magic-angle spinning (MAS) NMR spectroscopy and powder X-ray diffraction (PXRD) experiments, we present a comprehensive structural analysis of pyrophosphate-bearing calcium phosphate cements that are investigated for bone-inductive biomedical implants. The cements consist mainly of poorly ordered monetite (CaHPO4), along with minor Ca orthophosphate phases, and two distinct pyrophosphate constituents: crystalline beta-Ca2P2O7 and amorphous calcium pyrophosphate (ACPP), the latter involving one water bearing portion and another anhydrous component. Independent 2D MAS NMR experiments evidenced close contacts between the amorphous pyrophosphates and the monetite phase, where ACPP is proposed to form a thin layer coating the monetite particles. Heteronuclear H-1-P-31 and homonuclear P-31-P-31 correlation NMR experimentation enabled us to detect, identify, and quantify even minor cement constituents (less than or similar to 2 mol%) that could not be ascertained by the Rietveld method. Quantitative phase analyses of the cements, as determined independently by P-31 NMR and PXRD, are contrasted and discussed.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Bioceramics, Monetite cement, DCPA, Amorphous calcium pyrophosphate, P-31 NMR, H-1 NMR, 2D homonuclear/heteronuclear correlation, NMR spectroscopy, Rietveld refinement, Cement structure
National Category
Ceramics
Identifiers
urn:nbn:se:uu:diva-395715 (URN)10.1016/j.ceramint.2019.07.047 (DOI)000488148100128 ()
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
Sladkova, M., Cheng, J., Palmer, M., Chen, S., Lin, C., Xia, W., . . . de Peppo, G. M. (2019). Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells. Tissue Engineering. Part A, 25(3-4), 288-301
Open this publication in new window or tab >>Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells
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2019 (English)In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 25, no 3-4, p. 288-301Article in journal (Refereed) Published
Abstract [en]

Bone engineering makes it possible to grow unlimited amounts of viable tissue products for basic and applied research, and for clinical applications. A common trend in tissue engineering is the use of decellularized tissue matrices as scaffolding materials, which display structural, mechanical, and biological attributes typical of the native tissue. Due to the limited availability and high cost of human samples, decellularized tissue matrices are typically derived from animal sources. It is unclear, however, whether interspecies differences in tissue parameters will influence the quality of tissue grafts that are engineered using human stem cells. In this study, decellularized cow and human bone scaffolds were compared for engineering bone grafts using human induced pluripotent stem cell-derived mesodermal progenitor cells. After seeding, the cell-scaffold constructs were cultured for 5 weeks in osteogenic medium under dynamic conditions in perfusion bioreactors. The architectural and chemical properties of the scaffolds were studied using microscopic, spectroscopic, and thermogravimetric techniques, while cell behavior and formation of mineralized tissue were assessed using a combination of molecular assays, histological methods, and imaging technologies. The results show that while scaffolds derived from cow and human bone differ somewhat in architecture and composition, both equally support cell viability, tissue growth, and formation of a mineralized bone matrix. Taken together, the results suggest that scaffolds derived from cow bone represent a suitable and convenient alternative to engineer human bone grafts for various biomedical applications.

Keywords
biomaterial scaffold, bone engineering, induced pluripotent stem cells, mesenchymal stem cells, osteogenic differentiation, tissue decellularization
National Category
Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-369891 (URN)10.1089/ten.tea.2018.0149 (DOI)000448565100001 ()30129897 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-12-10Bibliographically approved
Atif, A. R., Pujari-Palmer, M., Tenje, M. & Mestres, G. (2019). Evaluation of Ionic Interactions of Bone Cement-on-Chip. In: : . Paper presented at 1st European Organ-on-Chips Society Conference, Graz, July 2-3, 2019.
Open this publication in new window or tab >>Evaluation of Ionic Interactions of Bone Cement-on-Chip
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

INTRODUCTION: Biomaterials are synthetic materials that can be incorporated into the body to replace an impaired physiological function. Apatite calcium phosphate cements (CPCs), used for bone regeneration, give calcium-deficient hydroxyapatite (CDHA) as an end-product after a dissolution-precipitation reaction during fabrication. CDHA has a tendency to uptake calcium and release phosphate into cell culture medium. Potentially, this leads to depletion of calcium ions in solution, which can be detrimental to cell survival. The aim of this work is to embed CDHA in a microfluidic system and evaluate ion exchange at different flow rates.

METHODS: CPC paste was cast into a 0.8mm pocket within a Polydimethylsiloxane (PDMS, cured at 60°C for 2h) mould. CPCs were set in 0.9% w/v NaCl at 37°C for 10 days resulting in CDHA. The PDMS containing the CDHA was then bonded to glass, leaving a 0.5mm channel gap. Minimum Essential Media (MEM, 1ml) was pumped through the channel at low (2µl/min), medium (8µl/min) and high (14µl/min) flow rates. A CDHA disc (ø=15mm, h=2mm) was immersed in MEM (1ml) at static conditions (0µl/min) for 24h. Stock Media was taken as control. Calcium and phosphorus concentrations were analysed using Inductively Coupled Plasma Optical Emission Spectroscopy.

RESULTS & CONCLUSIONS: CDHA was successfully embedded in a microfluidic chip (Fig. 1A). Observed [Ca] and [P] levels were closer to levels in stock MEM at higher flow rates (Fig. 1B). We anticipate that osteoblast viability will improve when grown under flow, as opposed to static conditions, due to continuous replenishment of cell medium.

National Category
Medical Materials
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-393088 (URN)
Conference
1st European Organ-on-Chips Society Conference, Graz, July 2-3, 2019
Funder
Swedish Research Council, 2017-05051Swedish Research Council Formas, 2016-00781Knut and Alice Wallenberg Foundation, 2016-0112Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, 1841
Available from: 2019-09-16 Created: 2019-09-16 Last updated: 2019-09-16Bibliographically approved
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
Pujari-Palmer, M., Guo, H., Wenner, D., Autefage, H., Spicer, C. D., Stevens, M. M., . . . Engqvist, H. (2018). A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials. Materials, 11(12), Article ID 2492.
Open this publication in new window or tab >>A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials
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2018 (English)In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 11, no 12, article id 2492Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
cement, tissue adhesive, phosphoserine, self-assembly, amorphous calcium phosphate (ACP), correlation nuclear magnetic resonance (NMR) spectroscopy, bioinspired, biomaterial
National Category
Composite Science and Engineering Ceramics Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-369970 (URN)10.3390/ma11122492 (DOI)000456419200150 ()30544596 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RMA15-0110
Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2019-02-18Bibliographically approved
Fu, L., Xiong, Y., Carlsson, G., Palmer, M., Örn, S., Zhu, W., . . . Xia, W. (2018). Biodegradable Si3N4 bioceramic sintered with Sr, Mg and Si for spinal fusion: Surface characterization and biological evaluation. Applied Materials Today, 12, 260-275
Open this publication in new window or tab >>Biodegradable Si3N4 bioceramic sintered with Sr, Mg and Si for spinal fusion: Surface characterization and biological evaluation
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2018 (English)In: Applied Materials Today, ISSN 2352-9407, Vol. 12, p. 260-275Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (Si3N4) is an industrial ceramic used in spinal fusion and maxillofacial reconstructionbecause of its excellent mechanical properties and good biocompatibility. This study compares the sur-face properties, apatite formation ability, bacterial infection, cell-biomaterial interactions, and in vivotoxicity (zebrafish) of newly developed Si3N4 bioceramics (sintered with bioactive sintering additivesSrO, MgO and SiO2) with two standard biomaterials; titanium (Ti) and traditional Si3N4 bioceramics (sin-tered with standard sintering additives Al2O3 and Y2O3). In general, Si3N4 bioceramics (both the newlydeveloped and the traditional) displayed less in vitro bacterial affinity than Ti, which may arise fromdifferences in the surface properties between these two types of material. The newly developed Si3N4bioceramics developed lower biofilm coverage and thinner biofilm, compared to traditional Si3N4 bioce-ramics. The effects of ionic dissolution products (leach) on proliferation and differentiation of MC3T3-E1cell were also investigated. Ionic dissolution products containing moderate amount of Sr, Mg and Siions (approximately 4.72 mg/L, 3.26 mg/L and 3.67 mg/L, respectively) stimulated osteoblast prolifera-tion during the first 2 days in culture. Interestingly, ionic dissolution products from the traditional Si3N4bioceramics that contained small amount of Si and Y ions achieved the greatest stimulatory effect foralkaline phosphatase activity after 7 days culture. The toxicity of ionic dissolution products was investi-gated in a putative developmental biology model: zebrafish (Danio rerio). No toxicity, or developmentalabnormalities, was observed in zebrafish embryos exposed to ionic dissolution products, for up to 144 hpost fertilization. These newly developed Si3N4 bioceramics with bioactive sintering additives show greatpotential as orthopedic implants, for applications such as spinal fusion cages. Future work will focus onevaluation of the newly developed Si3N4 bioceramics using a large animal model.

Keywords
Si3N4 bioceramic, Spinal fusion, Biocompatibility, Bioactive ions, Zebrafish
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-356522 (URN)10.1016/j.apmt.2018.06.002 (DOI)000443213700023 ()
Funder
Carl Tryggers foundation
Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2019-06-26Bibliographically approved
Atif, A. R., Carter, S.-S., Pujari-Palmer, M., Tenje, M. & Mestres, G. (2018). Bone Cement Embedded in a Microfluidic Device. In: : . Paper presented at Micronano System Workshop (MSW), May 13-15, 2018, Aalto University, Espoo, Finland.
Open this publication in new window or tab >>Bone Cement Embedded in a Microfluidic Device
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2018 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Calcium phosphate cements (CPCs) have a great potential in the treatment of bone disorders due to their excellent biocompatibility. Although CPCs are promising when implanted in vivo, there is poor correlation between in vitro and in vivo studies. This could be because most conventional in vitro systems lack a 3D architecture, or dynamic conditions (i.e. a continuous refreshment stream). The aim of this work is to embed CPCs into a microfluidic system and evaluate ion and protein exchange at different flow rates.

Keywords
Calcium Phosphate Cements, Microfluidic Chip, Continuous flow, Biomaterial Evaluation, Bone implants, Cells
National Category
Other Materials Engineering Engineering and Technology
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-363447 (URN)
Conference
Micronano System Workshop (MSW), May 13-15, 2018, Aalto University, Espoo, Finland
Funder
Swedish Research Council Formas, 2016-00781Knut and Alice Wallenberg Foundation, WAF 2016-0112Swedish Research Council, 2017-05051
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-12-04Bibliographically 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
Sladkova, M., Pujari-Palmer, M., Öhman, C., Cheng, J., Al-Ansari, S., Saad, M., . . . de Peppo, G. M. (2018). Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds. Journal of Tissue Engineering and Regenerative Medicine, 12(3), 715-726
Open this publication in new window or tab >>Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds
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2018 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 12, no 3, p. 715-726Article in journal (Refereed) Published
Abstract [en]

Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials, but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study, we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from bone marrow (BMSC). Biomimetic decellularized bone scaffolds were used as reference material in all experiments. The results demonstrate that, irrespective of their macroporosity, the CPC scaffolds tested in this study support attachment, viability, and growth of iPSC-MP and BMSC cells similarly to decellularized bone. Importantly, the tested materials sustained differentiation of the cells as evidenced by increased expression of osteogenic markers and formation of a mineralized tissue. In conclusion, the results of this study suggest that the CPC scaffolds fabricated using our method are suitable to engineer bone grafts from different cell sources and could lead to the development of safe and more affordable tissue grafts for reconstructive dentistry and orthopaedics and in vitro models for basic and applied research.

National Category
Other Medical Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-335996 (URN)10.1002/term.2491 (DOI)000427137100061 ()28635177 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-06-04Bibliographically approved
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