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BETA
Wistrand, Anna FinneORCID iD iconorcid.org/0000-0002-1922-128X
Alternative names
Publications (10 of 91) Show all publications
Ramani-Mohan, R.-K. -., Schwedhelm, I., Wistrand, A. F., Krug, M., Schwarz, T., Jakob, F., . . . Hansmann, J. (2018). Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation. Journal of Tissue Engineering and Regenerative Medicine, 12(3), e1474-e1479
Open this publication in new window or tab >>Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation
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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. e1474-e1479Article in journal (Refereed) Published
Abstract [en]

Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation. 

Place, publisher, year, edition, pages
John Wiley and Sons Ltd, 2018
Keywords
bioreactor, computational fluid dynamics, mechanical strain, mechanosensitive reporter gene constructs, mesenchymal stem cells, osteogenesis, 3 (4, 5 dimethyl 2 thiazolyl) 2, 5 diphenyltetrazolium bromide, alizarin red s, alkaline phosphatase, bone morphogenetic protein 2, collagen type 1, osteocalcin, osteonectin, osteopontin, transcription factor AP 1, transcription factor RUNX2, Article, bone deformation, bone development, bone mineralization, bone regeneration, bone remodeling, bone stress, cell culture, cell differentiation, cell lineage, cell maturation, controlled study, enzyme activity, gene expression, human, human cell, luciferase assay, mathematical model, mesenchymal stem cell, osteoblast, porosity, priority journal, quantitative analysis, shear stress, stem cell, stress, three dimensional imaging
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-227413 (URN)10.1002/term.2565 (DOI)000427137100016 ()2-s2.0-85043365425 (Scopus ID)
Note

Export Date: 9 May 2018; Article; Correspondence Address: Hansmann, J.; Translational Center Würzburg “Regenerative Therapies for Oncology and Musculosceletal Diseases”, Branch of Fraunhofer Institute for Interfacial Engineering and Biotechnology IGBGermany; email: jan.hansmann@uni-wuerzburg.de; Funding details: 242175, FP7, Seventh Framework Programme; Funding details: 13N12971— ETface, MOHESR, Ministry of Higher Education and Scientific Research; Funding text: Our work was funded by the German Federal Ministry of Education and Research, program NanoMatFutur, grant agreement 13N12971— ETface, and the European Union's Seventh Framework Program, grant agreement 242175—Vascubone. Furthermore, we thank Moustapha Kassem for providing the TERT cells. The authors woud also like to thank Ernst‐Ulrich Berndt for performing µ‐CT imaging on the scaffold. QC 20180530

Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2018-10-19Bibliographically approved
Sharma, S., Sapkota, D., Xue, Y., Rajthala, S., Yassin, M. A., Wistrand, A. F. & Mustafa, K. (2018). Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model. Stem Cell Research & Therapy, 9, Article ID 23.
Open this publication in new window or tab >>Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model
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2018 (English)In: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 9, article id 23Article in journal (Refereed) Published
Abstract [en]

Background: In bone tissue engineering (BTE), extensive research into vascular endothelial growth factor A (VEGFA)-mediated angiogenesis has yielded inconsistent results. The aim of this study was to investigate the influence on angio-and osteogenesis of adenoviral-mediated delivery of VEGFA alone or in combination with bone morphogenetic protein 2 (BMP2) in bone marrow stromal cells (BMSC) seeded onto a recently developed poly(LLA-co-CL) scaffold. Methods: Human BMSC were engineered to express VEGFA alone or in combination with BMP2 and seeded onto poly(LLA-co-CL) scaffolds. Changes in angiogenic and osteogenic gene and protein levels were examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR), PCR array, and alkaline phosphatase assay. An in vivo subcutaneous mouse model was used to investigate the effect on angio-and osteogenesis of VEGFA alone or in combination with BMP2, using microcomputed tomography (mu CT), histology, immunohistochemistry, and immunofluorescence. Results: Combined delivery of a lower ratio (1: 3) of VEGFA and BMP2 (ad-BMP2 + VEGFA) led to upregulation of osteogenic and angiogenic genes in vitro at 3 and 14 days, compared with mono-delivery of VEGFA (ad-VEGFA) and other controls. In vivo, in a subcutaneous mouse model, both ad-VEGFA and ad-BMP2 + VEGFA scaffold explants exhibited increased angiogenesis at 2 weeks. Enhanced angiogenesis was largely related to the recruitment and differentiation of mouse progenitor cells to the endothelial lineage and, to a lesser extent, to endothelial differentiation of the implanted BMSC. mu CT and histological analyses revealed enhanced de novo bone formation only in the ad-BMP2 + VEGFA group, corresponding at the molecular level to the upregulation of genes related to osteogenesis, such as ALPL, RUNX2, and SPP1. Conclusions: Although BMSC expressing VEGFA alone or in combination with BMP2 significantly induced angiogenesis, VEGFA alone failed to demonstrate osteogenic activity both in vitro and in vivo. These results not only call into question the use of VEGFA alone in bone regeneration, but also highlight the importance in BTE of appropriately formulated combined delivery of VEGFA and BMP2.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Bone regeneration, Scaffold, Mesenchymal stem cell, BMP2 and VEGFA, Angiogenesis, Gene delivery
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-223279 (URN)10.1186/s13287-018-0778-4 (DOI)000423686300006 ()29386057 (PubMedID)2-s2.0-85041627712 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 242175
Note

QC 20180219

Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-02-19Bibliographically approved
Yassin, M. A., Mustafa, K., Xing, Z., Sun, Y., Fasmer, K. E., Waag, T., . . . Leknes, K. N. (2017). A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration. Macromolecular Bioscience, 17(6), Article ID 1600427.
Open this publication in new window or tab >>A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration
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2017 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, no 6, article id 1600427Article in journal (Refereed) Published
Abstract [en]

Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-e-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/ nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2017
National Category
Polymer Technologies
Identifiers
urn:nbn:se:kth:diva-211398 (URN)10.1002/mabi.201600427 (DOI)000405565300006 ()2-s2.0-85019955880 (Scopus ID)
Note

QC 20170807

Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-07Bibliographically approved
Fuoco, T., Pappalardo, D. & Wistrand, A. F. (2017). Redox-Responsive Disulfide Cross-Linked PLA-PEG Nanoparticles. Macromolecules, 50(18), 7052-7061
Open this publication in new window or tab >>Redox-Responsive Disulfide Cross-Linked PLA-PEG Nanoparticles
2017 (English)In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 50, no 18, p. 7052-7061Article in journal (Refereed) Published
Abstract [en]

We have developed a strategy for the preparation of redox-responsive PEG PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly-(lactide)s were prepared by ring-opening copolymerization of L-lactide and 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167-300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-215816 (URN)10.1021/acs.macromol.7b01318 (DOI)000411918700006 ()2-s2.0-85029943967 (Scopus ID)
Note

QC 20171017

Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2017-10-17Bibliographically approved
Fuoco, T., Finne-Wistrand, A. & Pappalardo, D. (2016). A Route to Aliphatic Poly(ester)s with Thiol Pendant Groups: From Monomer Design to Editable Porous Scaffolds. Biomacromolecules, 17(4), 1383-1394
Open this publication in new window or tab >>A Route to Aliphatic Poly(ester)s with Thiol Pendant Groups: From Monomer Design to Editable Porous Scaffolds
2016 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 4, p. 1383-1394Article in journal (Refereed) Published
Abstract [en]

Biodegradable aliphatic polyesters such as poly(lactide) and poly(ϵ-caprolactone), largely used in tissue engineering applications, lack suitable functional groups and biological cues to enable interactions with cells. Because of the ubiquity of thiol groups in the biological environment and the pliability of thiol chemistry, we aimed to design and synthesize poly(ester) chains bearing pendant thiol-protected groups. To achieve this, 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a lactide-type monomer possessing a pendant thiol-protected group, was synthesized. This molecule, when used as a monomer in controlled ring-opening polymerization in combination with lactide and ϵ-caprolactone, appeared to be a convenient "building block" for the preparation of functionalized aliphatic copolyesters, which were easily modified further. A polymeric sample bearing pyridyl disulfide groups, able to bind a cysteine-containing peptide, was efficiently obtained from a two-step modification reaction. Porous scaffolds were then prepared by blending this latter copolymer sample with poly(l-lactide-co-ϵ-caprolactone) followed by salt leaching. A further disulfide exchange reaction performed in aqueous medium formed porous scaffolds with covalently linked arginine-glycine-aspartic acid sequences. The scaffolds were characterized by thermal and mechanical tests, and scanning electron microscopy surface images revealed a highly porous morphology. Moreover, a cytotoxicity test indicated good cell viability.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
Keywords
Ring-Opening Polymerization, Functionalized Poly(Lactic Acid), Dimethyl(Salicylaldiminato)Aluminum Compounds, Biomedical Applications, Epsilon-Caprolactone, O-Carboxyanhydrides, Peptide-Synthesis, Mercapto Groups, Amino-Acids, Polyesters
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-187075 (URN)10.1021/acs.biomac.6b00005 (DOI)000374076900016 ()26915640 (PubMedID)2-s2.0-84964661506 (Scopus ID)
Funder
VINNOVA, 201304323EU, FP7, Seventh Framework Programme, GROWTH 291795Swedish Research Council, 621-2013-3764
Note

QC 20160518

Available from: 2016-05-18 Created: 2016-05-17 Last updated: 2017-11-30Bibliographically approved
Bartaula-Brevik, S., Pedersen, T. O., Finne-Wistrand, A., Bolstad, A. I. & Mustafa, K. (2016). Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells. Tissue Engineering. Part A, 22(3-4), 244-252
Open this publication in new window or tab >>Angiogenic and Immunomodulatory Properties of Endothelial and Mesenchymal Stem Cells
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2016 (English)In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 22, no 3-4, p. 244-252Article in journal (Refereed) Published
Abstract [en]

It has been suggested that the effect of implanted cells on the local environment is important when selecting the appropriate cell type for tissue regeneration. Our aim was to compare the local tissue response to implanted human mesenchymal stem cells (MSC) and human umbilical vein endothelial cells (EC). MSC and EC were cultured in poly(l-lactide-co-1,5-dioxepan-2-one) scaffolds for 1 week in a bioreactor system, after which they were implanted subcutaneously in NOD/SCID mice. After 3 weeks, scaffolds were retrieved, and the mRNA expression of selected genes involved in hypoxia and inflammation was examined by real-time reverse transcription polymerase chain reaction and correlated with immunofluorescent staining for corresponding proteins. The Toll-like receptor signaling pathway was examined by superarray hybridization. The expression of 53 angiogenesis-related proteins was investigated by a proteome profiler angiogenesis antibody array kit. Vascularization was quantified using immunohistochemistry for CD31. The expression of hypoxia-inducible factors and biomarkers for angiogenesis was more strongly upregulated in response to implanted EC than to MSC, suggesting a higher sensitivity to low oxygen tension among EC. Hypoxic signaling was increased after implantation of EC compared with MSC, leading to a prolonged acute inflammatory phase that promoted ingrowth of vascular cells and establishment of the circulation. Inflammatory cytokines were also differently expressed at the gene and protein levels in the two experimental groups, resulting in altered recruitment of acute and chronic inflammatory cells. The end result of these differences was increased vessel formation within the constructs in the EC group.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2016
National Category
Cell Biology
Identifiers
urn:nbn:se:kth:diva-183333 (URN)10.1089/ten.tea.2015.0316 (DOI)000369987900007 ()26650611 (PubMedID)2-s2.0-84959062831 (Scopus ID)
Note

QC 20160308. QC 20160319

Available from: 2016-03-08 Created: 2016-03-07 Last updated: 2017-11-30Bibliographically approved
Suliman, S., Parajuli, H., Sun, Y., Johannessen, A. C., Finne-Wistrand, A., McCormack, E., . . . Costea, D. E. (2016). Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds. Head and Neck, 38, E1177-E1187
Open this publication in new window or tab >>Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds
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2016 (English)In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 38, p. E1177-E1187Article in journal (Refereed) Published
Abstract [en]

Background. Microenvironmental cues play a major role in head and neck cancer. Biodegradable scaffolds used for bone regeneration might also act as stimulative cues for head and neck cancer. The purpose of this study was to establish an experimental model for precise and noninvasive evaluation of tumorigenic potential of microenvironmental cues in head and neck cancer. Methods. Bioluminescence was chosen to image tumor formation. Early neoplastic oral keratinocyte (DOK) cells were luciferase-transduced (DOKLuc), then tested in nonobese diabetic severe combined immunodeficient IL2r gamma(null) mice either orthotopically (tongue) or subcutaneously for their potential as "screening sensors" for diverse microenvironmental cues. Results. Tumors formed after inoculation of DOKLuc were monitored easier by bioluminescence, and bioluminescence was more sensitive in detecting differences between various microenvironmental cues when compared to manual measurements. Development of tumors from DOKLuc grown on scaffolds was also successfully monitored noninvasively by bioluminescence. Conclusion. The model presented here is a noninvasive and sensitive model for monitoring the impact of various microenvironmental cues on head and neck cancer in vivo.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
cancer, microenvironment, bioluminescence, tissue engineering, scaffold
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:kth:diva-187826 (URN)10.1002/hed.24187 (DOI)000375116400148 ()2-s2.0-84939178723 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 242175
Note

QC 20160531

Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2016-05-31Bibliographically approved
Suliman, S., Sun, Y., Pedersen, T. O., Xue, Y., Nickel, J., Waag, T., . . . Mustafa, K. (2016). In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2. Advanced Healthcare Materials, 5(6), 730-742
Open this publication in new window or tab >>In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2
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2016 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 6, p. 730-742Article in journal (Refereed) Published
Abstract [en]

The aim is to evaluate the effect of modifying poly[(L-lactide)-co-(epsilon-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1 alpha 2, and ANGPT1 are signifi cantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates infl ammation while lowering the dose of BMP-2 to a relatively safe and economical level.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Materials Engineering
Identifiers
urn:nbn:se:kth:diva-185631 (URN)10.1002/adhm.201500723 (DOI)000373116400013 ()26853449 (PubMedID)2-s2.0-84961594126 (Scopus ID)
Note

QC 20160427

Available from: 2016-04-27 Created: 2016-04-25 Last updated: 2017-11-30Bibliographically approved
Suliman, S., Mustafa, K., Krueger, A., Steinmüller-Nethl, D., Finne-Wistrand, A., Osdal, T., . . . Costea, D. E. (2016). Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes. Biomaterials, 95, 11-21
Open this publication in new window or tab >>Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
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2016 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 95, p. 11-21Article in journal (Refereed) Published
Abstract [en]

This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOKLuc) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOKLuc previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOKLuc + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOKLuc both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOKLuc + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOKLuc, while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Biocompatibility, BMP-2, Bone tissue engineering, Microenvironment, Oral squamous cell carcinoma, Tumorigenicity, Bone, Cell culture, Cell engineering, Nanodiamonds, Room and pillar mining, Tissue engineering, Tumors, Microenvironments, Oral squamous cell carcinomata, Scaffolds (biology)
National Category
Bio Materials Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-186923 (URN)10.1016/j.biomaterials.2016.04.002 (DOI)2-s2.0-84963799400 (Scopus ID)
Note

QC 20160524

Available from: 2016-05-24 Created: 2016-05-16 Last updated: 2017-11-30Bibliographically approved
Skodje, A., Idris, S. B., Sun, Y., Bartaula, S., Mustafa, K., Finne-Wistrand, A., . . . Leknes, K. N. (2015). Biodegradable polymer scaffolds loaded with low-dose BMP-2 stimulate periodontal ligament cell differentiation. Journal of Biomedical Materials Research. Part A, 103(6), 1991-1998
Open this publication in new window or tab >>Biodegradable polymer scaffolds loaded with low-dose BMP-2 stimulate periodontal ligament cell differentiation
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2015 (English)In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 103, no 6, p. 1991-1998Article in journal (Refereed) Published
Abstract [en]

Poly(l-lactide)-co-(epsilon-caprolactone) [poly(LLA-co-CL)] and poly(l-lactide)-co-(1,5-dioxepan-2-one) [poly(LLA-co-DXO)] are being considered candidate scaffolds for bone tissue engineering. We evaluated the bioactive potential of poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds loaded with low-dose bone morphogenetic protein-2 (BMP-2). Periodontal ligament (PDL) cells were cultured onto the various scaffolds loaded with 1 μg BMP-2 or without BMP-2 (control). Cell viability, attachment, and proliferation were determined using a methylthiazol tetrazolium (MTT) colorimetric assay at day 1, 3, and 7. Scanning electron microscopy was used to analyze cell morphology at day 7. Cell differentiation was evaluated assaying alkaline phosphatase (ALP) activity at day 7, 14, and 21. Real-time PCR was used to evaluate the mRNA expression of periostin, ALP, type I collagen, bone sialoprotein and BMP-2. A commercially available enzyme-linked immunosorbent assay was used to assess BMP-2 production. Surface analysis disclosed excellent cell attachment, spread, and penetration into the porous scaffolds. The MTT assay indicated that scaffolds loaded with low concentration of BMP-2 did not influence the viability of cells. Cells grown on the modified scaffolds expressed higher levels of osteogenic markers than the nonmodified scaffolds (p<0.05). Poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds loaded with low-dose BMP-2 exhibited a significant effect stimulating PDL differentiation suggesting a continued evaluation in relevant in vivo models.

Keywords
bioengineering, BMP-2, cell biology, differentiation, polymer scaffolds, Biodegradable polymers, Biomaterials, Bone, Cells, Cytology, Differentiation (calculus), Phosphatases, Polymerase chain reaction, Scanning electron microscopy, Surface analysis, Systems science, Alkaline phosphatase activity, Biodegradable polymer scaffolds, Bone morphogenetic protein-2, Enzyme linked immunosorbent assay, Periodontal ligament cells, Scaffolds (biology)
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-167788 (URN)10.1002/jbm.a.35334 (DOI)000354024100010 ()25231842 (PubMedID)2-s2.0-84928584903 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 242175
Note

QC 20150525

Available from: 2015-05-25 Created: 2015-05-22 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1922-128X

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