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  • 1.
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Polyester scaffold: Material design and cell-protein-material interaction2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Konsten att med kroppens egna celler som utgångspunkt återskapa förlorad eller skadad vävnad, s.k. tissue engineering, har på senare tid blivit allt mer accepterad som ett alternativ  till dagens kliniska metoder. Inom ben-tissue engineering ingår oftast förutom celler, en nedbrytbar matris och lämpliga tillväxtfaktorer. För att kunna användas kliniskt ställs mycket höga krav på materialegenskaperna hos matrisen t.ex. dess utformning. Materialet ska vara biokompatibelt och matrisen ska i möjligaste mån efterlikna det naturliga proteinnätverk som finns mellan cellerna i benvävnaden. Eftertraktade egenskaper innefattar en 3-dimensionell porös struktur med förutsättnigar för adhesion, proliferering och differentiering av benceller.  Matrisens mekaniska egenskaper och nedbrytningshastighet är starkt beroende av varandra och bör anpassas efter den aktuella applikationen och vävnadens naturliga egenskaper.

    Den här avhandlingen beskriver utvecklandet av matriser baserade på alifatiska polyestrar med flera eftertraktade egenskaper inom ben-tissue egineering. Dessutom har alifatiska polyestrar används för att utveckla ett nytt mikrofluidikssystem för kontinuerlig visuell utvärdering av levande celler i porösa 3-dimensionella matriser.

    De nedbrytbara alifatiska polyestrarna poly(L-laktid-co-ε-kaprolakton) [poly(LLA-co-CL)], poly(L-laktid-co-1,5-dioxepan-2-on) [poly(LLA-co-DXO)] och poly(L-laktid) [poly(LLA)] användes för att tillverka matriser med hög grad av porositet, väl sammanbundna porer och varierande porstorlekar. De olika egenskaperna hos monomererna resulterade i matriser med mångsidiga egenskaper inom nedbrytningshastighet, mekanisk stabilitet, vätnings- och termiska-egenskaper.

    De framställda matriserna av alifatiska polyestrar visade sig stimulera proliferering och differentiering mot osteoblaster hos stamceller isolerade från benmärg (BMSC), vilket underströk potentialen hos dessa matriser för ben-tissue engineering. Vidare så förhöjdes potentialen hos poly(LLA-co-CL) matriser och andra kliniskt använda polyestrar genom att ytmodifiera materialen med den beninducerade tillväxtfaktorn, bone morphogenetic protein-2 (BMP-2). För detta ändamål utvecklades två separata immobiliseringsmetoder. I den ena metoden immobiliserades BMP-2 till heparinkopplade ytor och i den andra bands BMP-2 kovalent direkt till yt-ympade kopplingskedjor. I båda metoderna kunde BMP-2 immobiliseras med bibehållen biologisk aktivitet. Immobiliserat BMP-2 stimulerades i respektive metod till förhöjd proliferering hos embryonala C3H10T1/2 celler och ökat uttryck av gener starkt förknippade med mogna benceller samt proteinet osteocalcin i bencells-liknande celler.

    Nedbrytningsbeteendet och de mekaniska egenskaperna hos de elektronstråle-steriliserade polyestermatriser visade sig kraftigt beroende av materialens kemiska, fysiska och makroskopiska utfromning. Genom att inkorporera mer hydrofila monomerer i materialen påskyndades nedbrytningen och därmed förlusten av provens mekaniska stabilitet. Att istället sampolymerisera två hydrofoba monomerer med begränsade möjlighet till kristallisation, gav material med förlängd mekanisk stabilitet under nedbrytningen.

    BMSC och bencells-liknande celler visade normal utbredning och morfologi vid ahdesion till polyestrarna. Den initiala celladhesionen till syntetiska ytor sker vanligtvis genom ytadsorberade protein från omgivande biologiska vätskor. BMSCs initiala celladhesion till blodplasmabelagda polyestrar var starkt begränsade, oavsett polyestrarnas förmåga att adsorbera adhesiva protein ur blodplasma och att motsvarande proteinreceptorer återfanns på cellytan hos BMSC. Genom att istället adsorbera upprenade adhesiva protein till polyestrarna ökade adhesionen av BMSC till ytorna. Detta påvisade möjligheten att öka effektivitet av celladhesionen till polyestrar genom att på förhand belägga dem med adhesiva protein.

    Polyestrar kombinerades även med mikrofluidikteknik och mjuk litografi för att utveckla ett nytt system för högupplöst visuell observation av levande celler i porösa matriser. Systemet kunde användas till att kontinuerligt följa cell-proliferering och –differentiering på exakt samma plats i 3-dimensionella matriser under mer än 4 veckor. Det framtagna systemet kan med fördel användas till utvärdering av både material och celler som ska kan komma att användas inom tissue engineering.

    Slutsatsen blir att nedbrytbara matriser baserade på alifatiska polyester som grundligt utformas i avseende på makroskopisk struktur, bulkmaterial och ytkemi kan möta kraven för olika applikationer inom ben-tissue engineering. Dessutom kan alifatiska polyestrar kombineras med mikrofluidiskt system för att tillåta kontinuerligt högupplös visualisering av levande celler i porösa matriser med stor potential som utvärderingsmetod inom tissue engineering.

  • 2.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Patarroyo, Manuel
    Institutionen for Odontologi, Karolinska Institute.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces2012Ingår i: Biomedical Materials, ISSN 1748-6041, E-ISSN 1748-605X, Vol. 7, nr 3, s. 035011-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin.

  • 3.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Edlund, Ulrica
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Enhanced Osteoconductivity of Degradable co-Polyester Scaffolds through Covalent Immobilization of BMP-2Manuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Schander, K.
    Hakkarainen, Minna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Arvidson, K.
    Mustafa, K.
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    In vitro and in vivo degradation profile of aliphatic polyesters subjected to electron beam sterilization2011Ingår i: ACTA BIOMATERIALIA, ISSN 1742-7061, Vol. 7, nr 5, s. 2035-2046Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Degradation characteristics in response to electron beam sterilization of designed and biodegradable aliphatic polyester scaffolds are relevant for clinically successful synthetic graft tissue regeneration Scaffold degradation in vitro and in vivo were documented and correlated to the macroscopic structure and chemical design of the original polymer The materials tested were of inherently diverse hydrophobicity and crystallinity poly(L-lactide) (poly(LLA)) and random copolymers from L-lactide and epsilon-caprolactone or 1.5-dioxepan-2-one, fabricated into porous and non-porous scaffolds After sterilization, the samples underwent hydrolysis in vitro for up to a year In vivo, scaffolds were surgically implanted into rat calvarial defects and retrieved for analysis after 28 and 91 days In vitro, poly(L-lactide-co-1, 5-dioxepan-2-one) (poly(LLA-co-DXO)) samples degraded most rapidly during hydrolysis, due to the pronounced chain-shortening reaction caused by the sterilization. This was indicated by the rapid decrease in both mass and molecular weight of poly(LLA-co-DXO). Poly(L-lactide-co-epsilon-caprolactone) (poly(LLA-co-CL)) samples were also strongly affected by sterilization, but mass loss was more gradual; molecular weight decreased rapidly during hydrolysis Least affected by sterilization were the poly(LLA) samples, which subsequently showed low mass loss rate and molecular weight decrease during hydrolysis. Mechanical stability varied greatly. poly(LLA-co-CL) withstood mechanical testing for up to 182 days, while poly(LLA) and poly(LLA-co-DXO) samples quickly became too brittle Poly(LLA-co-DXO) samples unexpectedly degraded more rapidly in vitro than in vivo. After sterilization by electron beam irradiation, the three biodegradable polymers present widely diverse degradation profiles, both in vitro and in vivo. Each exhibits the potential to be tailored to meet diverse clinical tissue engineering requirements

  • 5.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Gladnikoff, Micha
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Frisk, Thomas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Mustafa, Kamal
    Russom, Aman
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Development of a novel microfluidic device for long-term in situ monitoring of live cells in 3-dimensional matrices2012Ingår i: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 14, nr 5, s. 885-893Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using the latest innovations in microfabrication technology, 3-dimensional microfluidic cell culture systems have been developed as an attractive alternative to traditional 2-dimensional culturing systems as a model for long-term microscale cell-based research. Most microfluidic systems are based on the embedding of cells in hydrogels. However, physiologically realistic conditions based on hydrogels are difficult to obtain and the systems are often too complicated. We have developed a microfluidic cell culture device that incorporates a biodegradable rigid 3D polymer scaffold using standard soft lithography methods. The device permits repeated high-resolution fluorescent imaging of live cell populations within the matrix over a 4 week period. It was also possible to track cell development at the same spatial location throughout this time. In addition, human primary periodontal ligament cells were induced to produce quantifiable calcium deposits within the system. This simple and versatile device should be readily applicable for cell-based studies that require long-term culture and high-resolution bioimaging.

  • 6.
    Dånmark, Staffan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Gladnikoff, Micha
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Frisk, Thomas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Zelenina, Marina
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Russom, Aman
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Polymerteknologi.
    Development of Novel Microfluidic Device for Long-Term in situ Monitoring of Live Cells in 3-dimensional MatricesManuskript (preprint) (Övrigt vetenskapligt)
  • 7. Idris, Shaza B.
    et al.
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Finne Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Arvidson, Kristina
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Bolstad, Anne Isine
    Mustafa, Kamal
    Biocompatibility of Polyester Scaffolds with Fibroblasts and Osteoblast-like Cells for Bone Tissue Engineering2010Ingår i: Journal of bioactive and compatible polymers (Print), ISSN 0883-9115, E-ISSN 1530-8030, Vol. 25, nr 6, s. 567-583Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to evaluate the in vitro cytotoxicity and cytocompatibility of the developed aliphatic polyester co-polymer scaffolds: poly(L-lactide-co-epsilon-caprolactone) and poly(L-lactide-co-1,5-dioxepan-2-one). The scaffolds were produced by solvent casting and particulate leaching, and tested by direct and indirect contact cytotoxicity assays on human osteoblast-like cells and mouse fibroblasts. Cell morphology was documented by light and scanning electron microscopy. Viability was assessed by the MTT, neutral red uptake, lactic dehydrogenase and apoptosis assays. Extraction tests confirmed that the scaffolds did not have a cytotoxic effect on the cells. The cells grew and spread well on the test scaffolds with good cellular attachment and viability. The scaffolds are noncytotoxic and biocompatible with the two cell types and warrant continued investigation as potential constructs for bone tissue engineering.

  • 8. Idris, Shaza B.
    et al.
    Isine Bolstad, Anne
    Ibrahim, Saleh O.
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Finne Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Arvidsson, Kristina
    Mustafa, Kamal
    Global Gene Expression Profile of Osteoblast-Like Cells Grown on Polyester Copolymer Scaffolds2011Ingår i: Tissue Engineering. Part A, ISSN 1937-3341, Vol. 17, nr 21-22, s. 2817-2831Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the principal goals in tissue engineering is to produce scaffold materials that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. Poly(l-lactide-co-1,5-dioxepan-2-one) [Poly(LLA-co-DXO)], a potential scaffolding material for bone tissue engineering, has high hydrophilicity. Previous in vitro studies using human osteoblast-like cells (HOBs) demonstrated greater cytocompatibility and enhanced osteogenic differentiation when HOBs were seeded onto Poly(LLA-co-DXO) compared to Poly(llactide) [P(LLA)] scaffolds. The aim of the study was to identify the gene expression profiles of HOBs obtained from alveolar bone and grown on Poly(LLA-co-DXO) biodegradable polymer scaffolds compared to P(LLA) one. Illumina HumanWG-6 v3.0 Expression BeadChips were used for the gene expression analysis. Several genes were found as differentially expressed at 24 h and at 21 days. Expression of genes related to cell adhesion, cytoskeleton, antiapoptosis, proliferation, and bone mineralization was influenced by adding the monomer 1,5-dioxepan-2-one to the l-lactide. Genes related to three biological pathways involving Integrin, Notch, and Ras were found to be upregulated. For selected genes, results were confirmed by quantitative reverse transcriptase– polymerase chain reaction. Further, calcium content analysis revealed a significant enhancement of calcium deposition on both tested scaffolds. This observation was confirmed by Von Kossa and Alizarin Red S staining. Findings of this study are relevant to a better understanding of the molecular mechanisms underlying the behavior of HOBs in bone regenerative procedure.

  • 9. Li, Yan
    et al.
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Edlund, Ulrica
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    He, Xu
    Norgard, Maria
    Blomen, Eva
    Hultenby, Kjell
    Andersson, Goran
    Lindgren, Urban
    Resveratrol-conjugated poly-epsilon-caprolactone facilitates in vitro mineralization and in vivo bone regeneration2011Ingår i: ACTA BIOMATERIALIA, ISSN 1742-7061, Vol. 7, nr 2, s. 751-758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Incorporation of osteoinductive factors in a suitable scaffold is considered a promising strategy for generating osteogenic biomaterials. Resveratrol is a polyphenol found in parts of certain plants, including nuts, berries and grapes. It is known to increase DNA synthesis and alkaline phosphatase (ALP) activity in osteoblasts and to prevent femoral bone loss in ovariectomized (OVX) rats. In the present study resveratrol was coupled through a hydrolysable covalent bond with the carboxylic acid groups in porous poly-epsilon-caprolactone (PCL) surface grafted with acrylic acid (AA). The osteogenic effect of this new scaffold was evaluated in mesenchymal cell culture and in the rat calvarial defect model. We found that the incorporation of resveratrol caused increased ALP activity of rat bone marrow stromal cells and enhanced mineralization of the cell-scaffold composites in vitro. After 8 weeks the calvarial defects implanted with resveratrol-conjugated PCL displayed a higher X-ray density than the defects implanted with control PCL. Bone-like structures, positively immunostained for bone sialoprotein, were shown to be more extensively formed in the resveratrol-conjugated PCL These results show that incorporation of resveratrol into the AA-functionalized porous PCL scaffold led to a significant increase in osteogenesis. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 10. Xing, Zhe
    et al.
    Xue, Ying
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Finne-Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Arvidson, Kristina
    Hellem, Solve
    Yang, Zhuang-Qun
    Mustafa, Kamal
    Comparison of short-run cell seeding methods for poly(L-lactide-co-1,5-dioxepan-2-one) scaffold intended for bone tissue engineering2011Ingår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 34, nr 5, s. 432-441Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Constructs intended for bone tissue engineering are influenced by the initial cell seeding procedure. The seeding method should be rapid, convenient, improve cell spatial distribution, and have no negative effects on cellular viability and differentiation. This study aimed to compare the effect of short-run seeding methods (centrifuge and vortex) with a static method on the scaffolds prepared from poly(L-lactide-co-1,5-dioxepan-2-one) by solvent-casting particulate-leaching (SCPL) technique. Human osteoblast-like cells (HOB) were seeded by the three methods described above. The seeding efficiency was determined by attached cell numbers. Cellular proliferation was analyzed by WST-1 and dsDNA assay. Cell distribution was examined by scanning electron (SEM) and fluorescence microscopy. Expression of Alkaline Phosphatase (ALP), Collagen type I (Col I), Osteocalcin (OC) and Proliferating Cell Nuclear Antigen (PCNA) were determined by real time RT-PCR. Results indicated that centrifuge and vortex increased seeding efficiency and had no negative effects on cellular viability. The data obtained by the fluorescence microscope confirmed the SEM results that the vortex method improved cell distribution through the scaffolds more than the other two methods (p<0.05). The RT-PCR results showed no significant differences on the expression of mRNA between the three methods of the above markers. The vortex method was found to be a simple and feasible seeding method for the poly(L-lactide-co-1,5-dioxepan-2-one) scaffolds.

  • 11. Xing, Zhe
    et al.
    Xue, Ying
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Schander, Kerstin
    Ostvold, Siren
    Arvidson, Kristina
    Hellem, Solve
    Finne Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Mustafa, Kamal
    Effect of endothelial cells on bone regeneration using poly(L-lactide-co-1,5-dioxepan-2-one) scaffolds2011Ingår i: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 96A, nr 2, s. 349-357Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our recent in vitro study demonstrated that endothelial cells (ECs) might influence the differentiation of bone marrow stromal cells (BMSCs). Therefore, the aim of this study was to describe this effect in vivo, using a rat calvarial bone defect model. BMSCs were isolated from femurs of two-donor Lewis rats and expanded in alpha-minimum essential medium containing 10% fetal bovine serum. One fifth of BMSCs were induced and differentiated into ECs in an Endothelial Cell Growth Medium-2 and then characterized by a flow cytometry. The remaining BMSCs were cultured in freshly prepared osteogenic stimulatory medium, containing dexamethasone, ascorbic acid and beta-glycerophosphate. Either BMSCs alone (BMSC-group) or co-cultured ECs/BMSCs (CO-group) were seeded into poly(L-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds, cultured in spinner flasks, and then implanted into symmetrical calvarial defects prepared in recipient rats. The animals were sacrificed after 2 months. The formation of new bone was evaluated by radiography and histology and by the expression of osteogenic markers using reverse transcriptase-polymerized chain reaction (RT-PCR). To investigate vessel formation, histological staining was performed with EC's markers. The radiographical and histological results showed more rapid bone formation in the CO-than in the BMSC-group. However, the expression of EC's marker was similar on both groups by histological analysis after 2 months postoperatively. Furthermore, the CO-group exhibited greater expression of osteogenic markers as demonstrated by RT-PCR. The results are consistent with the previous in vitro findings that poly(LLA-co-DXO) scaffold might be suitable candidate for bone tissue engineering. In vivo, bone regeneration was enhanced by a construct of the polymer scaffold loaded with co-cultured cells.

  • 12. Xue, Ying
    et al.
    Dånmark, Staffan
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik.
    Xing, Zhe
    Arvidson, Kristina
    Albertsson, Ann-Christine
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Hellem, Solve
    Finne Wistrand, Anna
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknik, Polymerteknologi.
    Mustafa, Kamal
    Growth and differentiation of bone marrow stromal cells on biodegradable polymer scaffolds: An in vitro study2010Ingår i: Journal of Biomedical Materials Research - Part A, ISSN 1549-3296, Vol. 95A, nr 4, s. 1244-1251Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A fundamental component of bone tissue engineering is an appropriate scaffold as a carrier for osteogenic cells. The aim of the study was to evaluate the response of human bone marrow stromal cells (BMSC) to scaffolds made of three biodegradable polymers: poly(L-lactide-co-epsilon-caprolactone) (poly(LLA-co-CL)), poly(L-lactide-co-1,5dioxepan-2-one) (poly(LLA-co-DXO)), and poly(L-lactide) (poly(LLA)). Cellular response was evaluated in terms of attachment, proliferation, and differentiation. SEM disclosed earlier cell attachment and better spreading on poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds than on poly(LLA) after 1 h. At 24 h and 14 days postseeding, BMSCs had spread well, forming multiple cellular layers on the scaffolds. Cell proliferation was higher on poly(LLA-co-CL) and on poly(LLA-co-DXO) than on poly(LLA) after 1 and 7 days. Cell growth cycles of BMSC were longer on the scaffolds than on coverslips. After 7 and 14 days cultivation on scaffolds, the expression of osteogenic markers such as ALP, Col I, OPN, and Runx2 were stimulated by BMSC, which indicating that poly(LLA-co-DXO), poly(LLA-co-CL), and poly(LLA) could support the osteogenic differentiation of BMSC in vitro. Poly(LLA-co-CL) and poly(LLA-co-DXO) promoted better attachment and growth of BMSC than poly(LLA). BMSC also retained their osteogenic differentiation potential, indicating biological activity of BMSC on the scaffolds. The promising results of this in vitro study indicate that these copolymers warrant further evaluation for potential application in bone tissue engineering.

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