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Mestres, G., Perez, R. A., d'Elía, N. & Barbe, L. (2019). Advantages of microfluidic systems for studying cell-biomaterial interactions: focus on bone regeneration applications. Biomedical Physics & Engineering Express, 5(3), Article ID 032001.
Öppna denna publikation i ny flik eller fönster >>Advantages of microfluidic systems for studying cell-biomaterial interactions: focus on bone regeneration applications
2019 (Engelska)Ingår i: Biomedical Physics & Engineering Express, ISSN 2057-1976, Vol. 5, nr 3, artikel-id 032001Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

The poor correlation between in vitro and in vivo studies emphasises the lack of a reliable methodology for testing the biological properties of biomaterials in the bone tissue regeneration field. Moreover, the success of clinical trials is not guaranteed even with promising results in vivo. Therefore, there is a need for a more physiologically relevant in vitro model to test the biological properties of biomaterials. Microfluidics, which is a field concerning the manipulation and control of liquids at the submillimetre scale, can use channel geometry, cell confinement and fluid flow to recreate a physiological-like environment. This technology has already proven to be a powerful tool in studying the biological response of cells in defined environments, since chemical and mechanical inputs as well as cross-talk between cells can be finely controlled. Moving a step further in complexity, biomaterials can be integrated into microfluidic systems to evaluate biomaterial-cell interactions. The biomaterial- microfluidics combination has the potential to produce more physiologically relevant models to better screen the biological interactions established between biomaterials and cells. This review is divided into two main sections. First, several possible cell-based assays for bone regeneration studies in microfluidic systems are discussed. Second, and the ultimate goal of the review, is to discuss how the gap between in vitro and in vivo studies can be shortened by bridging the biomaterials and microfluidics fields.

Nyckelord
bone regeneration, biomaterials, in vitro, microfluidics, microsystems, cell culture
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-381400 (URN)10.1088/2057-1976/ab1033 (DOI)000463561300001 ()
Forskningsfinansiär
Forskningsrådet Formas, 2016-00781Vetenskapsrådet, 2017-05051Göran Gustafssons stiftelse för naturvetenskaplig och medicinsk forskning (KVA), 1841Stiftelsen för internationalisering av högre utbildning och forskning (STINT), IB2017-7362
Tillgänglig från: 2019-04-09 Skapad: 2019-04-09 Senast uppdaterad: 2019-04-25Bibliografiskt granskad
D’Elía, N. L., Rial Silva, R., Sartuqui, J., Ercoli, D., Ruso, J., Messina, P. & Mestres, G. (2019). Alginate - hydroxyapatite composites for guided bone regeneration: rheology and tensile strength. In: : . Paper presented at SAP 2019 (Simposio Argentino de Polimeros), Buenos Aires, Argentina, 9-11 october 2019.
Öppna denna publikation i ny flik eller fönster >>Alginate - hydroxyapatite composites for guided bone regeneration: rheology and tensile strength
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2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Nyckelord
biomaterials, bone regeneration
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-392967 (URN)
Konferens
SAP 2019 (Simposio Argentino de Polimeros), Buenos Aires, Argentina, 9-11 october 2019
Tillgänglig från: 2019-09-11 Skapad: 2019-09-11 Senast uppdaterad: 2019-09-16Bibliografiskt granskad
Blasi Romero, A., Nguyen, H., Barbe, L., Tenje, M. & Mestres, G. (2019). Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties. In: : . Paper presented at 2nd European Organ-on-Chip Conference (EUROoC 2019), 2-3 July 2019, Graz, Austria.
Öppna denna publikation i ny flik eller fönster >>Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties
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2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Nyckelord
Biomaterials, biomaterials-on-chip, microfluidics
Nationell ämneskategori
Medicinska material och protesteknik
Identifikatorer
urn:nbn:se:uu:diva-392966 (URN)
Konferens
2nd European Organ-on-Chip Conference (EUROoC 2019), 2-3 July 2019, Graz, Austria
Tillgänglig från: 2019-09-11 Skapad: 2019-09-11 Senast uppdaterad: 2019-09-16Bibliografiskt granskad
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.
Öppna denna publikation i ny flik eller fönster >>Evaluation of Ionic Interactions of Bone Cement-on-Chip
2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
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.

Nationell ämneskategori
Medicinska material och protesteknik
Forskningsämne
Teknisk fysik med inriktning mot mikrosystemteknik
Identifikatorer
urn:nbn:se:uu:diva-393088 (URN)
Konferens
1st European Organ-on-Chips Society Conference, Graz, July 2-3, 2019
Forskningsfinansiär
Vetenskapsrådet, 2017-05051Forskningsrådet Formas, 2016-00781Knut och Alice Wallenbergs Stiftelse, 2016-0112Göran Gustafssons stiftelse för naturvetenskaplig och medicinsk forskning (KVA), 1841
Tillgänglig från: 2019-09-16 Skapad: 2019-09-16 Senast uppdaterad: 2019-09-16Bibliografiskt granskad
Mestres, G., Fernandez-Yague, M. A., Pastorino, D., Montufar, E. B., Canal, C., Manzanares-Céspedes, M.-C. & Ginebra, M.-P. (2019). In vivo efficiency of antimicrobial inorganic bone grafts in osteomyelitis Treatments. Materials science & engineering. C, biomimetic materials, sensors and systems, 97, 84-95
Öppna denna publikation i ny flik eller fönster >>In vivo efficiency of antimicrobial inorganic bone grafts in osteomyelitis Treatments
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2019 (Engelska)Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, s. 84-95Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 μm vs. macroporosity, i.e. >5 μm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.

Nyckelord
Osteomyelitis; Calcium phosphate cements; Calcium phosphate foams; Magnesium phosphate cements; Drug delivery; In vivo
Nationell ämneskategori
Biomaterialvetenskap
Forskningsämne
Teknisk fysik med inriktning mot materialvetenskap
Identifikatorer
urn:nbn:se:uu:diva-369961 (URN)10.1016/j.msec.2018.11.064 (DOI)000457952800009 ()30678975 (PubMedID)
Anmärkning

De 2 första författarna delar förstaförfattarskapet.

Tillgänglig från: 2018-12-17 Skapad: 2018-12-17 Senast uppdaterad: 2019-03-08Bibliografiskt granskad
Carter, S.-S., Nguyen, H., Moreira, M., Tenje, M. & Mestres, G. (2019). Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration. In: : . Paper presented at 2nd European Organ-on-Chip Conference, EUROoC 2019, Graz, Austria, July 2-3, 2019.
Öppna denna publikation i ny flik eller fönster >>Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration
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2019 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Abstract [en]

Medical grade titanium on-chip: assessing the biological properties of biomaterials for bone regeneration

 

Sarah-Sophia D. Carter1, Hugo Nguyen2, Milena Moreira1, Maria Tenje1, and Gemma Mestres1

1Department of Engineering Sciences, Science for Life Laboratory, Uppsala University, Sweden

2Department of Engineering Sciences, Uppsala University, Sweden

 

Introduction

Before entering the clinic, biomaterials need to be thoroughly evaluated, which requires accurate in vitro models. In this work, we have developed a microfluidic device that could be used to assess the biological properties of biomaterials, in a more in vivo-like environment than what is currently possible.

 

Methods

Our device consists of a polydimethylsiloxane (PDMS, Sylgard 184) microfluidic channel (l= 6 mm, w= 2 mm, h= 200 µm) and a titanium disc (Ti6Al4V, at bottom), held together by an additively manufactured fixture (Fig. 1A). PDMS was cured overnight at 65°C on a silicon wafer master. Once the microchannel and titanium disc were positioned, MC3T3-E1 pre-osteoblast-like cells were seeded (50,000 cells/cm2). After 5 hours incubation under standard culture conditions, flow was started (2 μl/min). As a control, MC3T3-E1 cells were seeded onto plain titanium discs off-chip. Cell viability and morphology were assessed after 20 hours by calcein-AM/propidium iodide (PI), staining live and dead cells respectively.

 

Results and discussion

Figure 1B and 1C show calcein-AM/PI stained MC3T3-E1 cells cultured on-chip and figure 1D shows the control, MC3T3-E1 cells cultured off-chip. The potential to culture cells in our chip was confirmed by the presence of a majority of viable cells (green) with a similar morphology as the control sample. The reason for the increased amount of dead cells (red) on-chip compared to the control needs to be further examined, which requires longer-term experiments.

Conclusion

We have set the first steps towards a microfluidic tool for the assessment of biological properties of biomaterials.

Nyckelord
Organ-on-chip, biomaterials, microfluidics
Nationell ämneskategori
Teknik och teknologier
Forskningsämne
Teknisk fysik med inriktning mot mikrosystemteknik
Identifikatorer
urn:nbn:se:uu:diva-393277 (URN)
Konferens
2nd European Organ-on-Chip Conference, EUROoC 2019, Graz, Austria, July 2-3, 2019
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, WAF 2016-0112Vattenfall AB, 2017-05051
Tillgänglig från: 2019-09-18 Skapad: 2019-09-18 Senast uppdaterad: 2019-09-20Bibliografiskt granskad
Diez-Escudero, A., Liu, Y., Lançon, V., Widhe, M., Persson, C., Hedhammar, M. & Mestres, G. (2019). Recombinant silk with calcium phosphates as macroporous bone scaffolds. In: : . Paper presented at European Congress and Exhibition on advanced materials and processes (EUROMAT 2019), 1-5 September 2019, Stockholm, Sweden.
Öppna denna publikation i ny flik eller fönster >>Recombinant silk with calcium phosphates as macroporous bone scaffolds
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2019 (Engelska)Konferensbidrag, Enbart muntlig presentation (Refereegranskat)
Nyckelord
Biomaterials, calcium phosphate cements, porosity
Nationell ämneskategori
Materialteknik
Identifikatorer
urn:nbn:se:uu:diva-392965 (URN)
Konferens
European Congress and Exhibition on advanced materials and processes (EUROMAT 2019), 1-5 September 2019, Stockholm, Sweden
Tillgänglig från: 2019-09-11 Skapad: 2019-09-11 Senast uppdaterad: 2019-09-16Bibliografiskt granskad
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.
Öppna denna publikation i ny flik eller fönster >>Bone Cement Embedded in a Microfluidic Device
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2018 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Refereegranskat)
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.

Nyckelord
Calcium Phosphate Cements, Microfluidic Chip, Continuous flow, Biomaterial Evaluation, Bone implants, Cells
Nationell ämneskategori
Annan materialteknik Teknik och teknologier
Forskningsämne
Teknisk fysik med inriktning mot mikrosystemteknik
Identifikatorer
urn:nbn:se:uu:diva-363447 (URN)
Konferens
Micronano System Workshop (MSW), May 13-15, 2018, Aalto University, Espoo, Finland
Forskningsfinansiär
Forskningsrådet Formas, 2016-00781Knut och Alice Wallenbergs Stiftelse, WAF 2016-0112Vetenskapsrådet, 2017-05051
Tillgänglig från: 2018-10-18 Skapad: 2018-10-18 Senast uppdaterad: 2018-12-04Bibliografiskt granskad
Carter, S.-S., Atif, A. R., Lanekoff, I., Tenje, M. & Mestres, G. (2018). Improving the biocompatibility of PDMS by improving its curing time and temperature. In: : . Paper presented at EUROoC (organ on a chip), 24-25 May 2018, Stuttgart, Germany.
Öppna denna publikation i ny flik eller fönster >>Improving the biocompatibility of PDMS by improving its curing time and temperature
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2018 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Övrigt vetenskapligt)
Nyckelord
Organ-on-chip, Biocompatibility, PDMS
Nationell ämneskategori
Teknik och teknologier
Forskningsämne
Teknisk fysik med inriktning mot mikrosystemteknik
Identifikatorer
urn:nbn:se:uu:diva-353156 (URN)
Konferens
EUROoC (organ on a chip), 24-25 May 2018, Stuttgart, Germany
Forskningsfinansiär
Forskningsrådet Formas, 2016-00781Knut och Alice Wallenbergs Stiftelse, WAF 2016-0112Vetenskapsrådet, 2017-05051
Tillgänglig från: 2018-06-11 Skapad: 2018-06-11 Senast uppdaterad: 2018-12-11
Carter, S.-S., Atif, A., Lanekoff, I., Tenje, M. & Mestres, G. (2018). Tailoring the biocompatibility of the elastomer PDMS for on-chip applications. In: : . Paper presented at Scandinavian Society for Biomaterials, April 25-27th 2018, Gullmarsstrand, Sweden.
Öppna denna publikation i ny flik eller fönster >>Tailoring the biocompatibility of the elastomer PDMS for on-chip applications
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2018 (Engelska)Konferensbidrag, Poster (med eller utan abstract) (Refereegranskat)
Nyckelord
PDMS, biocompatibility, organ-on-chip
Nationell ämneskategori
Teknik och teknologier
Forskningsämne
Teknisk fysik med inriktning mot mikrosystemteknik
Identifikatorer
urn:nbn:se:uu:diva-353152 (URN)
Konferens
Scandinavian Society for Biomaterials, April 25-27th 2018, Gullmarsstrand, Sweden
Forskningsfinansiär
Forskningsrådet Formas, 2016-00781Vetenskapsrådet, 2017-05051Knut och Alice Wallenbergs Stiftelse, WAF 2016-0112
Tillgänglig från: 2018-06-11 Skapad: 2018-06-11 Senast uppdaterad: 2018-12-11
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-7462-4236

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