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  • 1.
    Alarcon, Emilio I.
    et al.
    University of Ottawa, Canada; University of Ottawa, Canada; University of Ottawa, Canada.
    Udekwu, Klas I.
    Karolinska Institute, Sweden.
    Noel, Christopher W.
    University of Ottawa, Canada; .
    Gagnon, Luke B. -P.
    University of Ottawa, Canada.
    Taylor, Patrick K.
    University of Ottawa, Canada.
    Vulesevic, Branka
    University of Ottawa, Canada.
    Simpson, Madeline J.
    University of Ottawa, Canada.
    Gkotzis, Spyridon
    Karolinska Institute, Sweden.
    Islam, Mohammed Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Richter-Dahlfors, Agneta
    Karolinska Institute, Sweden.
    Mah, Thien-Fah
    University of Ottawa, Canada.
    Suuronen, Erik J.
    University of Ottawa, Canada.
    Scaiano, Juan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Ottawa, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Safety and efficacy of composite collagen-silver nanoparticle hydrogels as tissue engineering scaffolds2015Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 7, nr 44, s. 18789-18798Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The increasing number of multidrug resistant bacteria has revitalized interest in seeking alternative sources for controlling bacterial infection. Silver nanoparticles (AgNPs), are amongst the most promising candidates due to their wide microbial spectrum of action. In this work, we report on the safety and efficacy of the incorporation of collagen coated AgNPs into collagen hydrogels for tissue engineering. The resulting hybrid materials at [AgNPs] less than0.4 mu M retained the mechanical properties and biocompatibility for primary human skin fibroblasts and keratinocytes of collagen hydrogels; they also displayed remarkable anti-infective properties against S. aureus, S. epidermidis, E. coli and P. aeruginosa at considerably lower concentrations than silver nitrate. Further, subcutaneous implants of materials containing 0.2 mu M AgNPs in mice showed a reduction in the levels of IL-6 and other inflammation markers (CCL24, sTNFR-2, and TIMP1). Finally, an analysis of silver contents in implanted mice showed that silver accumulation primarily occurred within the tissue surrounding the implant.

  • 2.
    Buznyk, Oleksiy
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. National Academic Medical Science Ukraine, Ukraine.
    Pasyechnikova, Nataliya
    National Academic Medical Science Ukraine, Ukraine.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Iakymenko, Stanislav
    National Academic Medical Science Ukraine, Ukraine.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Bioengineered Corneas Grafted as Alternatives to Human Donor Corneas in Three High-Risk Patients2015Ingår i: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 8, nr 5, s. 558-562Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial.

  • 3.
    He, Min
    et al.
    Harvard Medical Sch, MA USA; Shanxi Medical University, Peoples R China.
    Storr-Paulsen, Thomas
    Harvard Medical Sch, MA USA; Aarhus University Hospital NBG, Denmark.
    Wang, Annie L.
    Harvard Medical Sch, MA USA.
    Ghezzi, Chiara E.
    Tufts University, MA 02155 USA.
    Wang, Siran
    Tufts University, MA 02155 USA.
    Fullana, Matthew
    Case Western Reserve University, OH 44106 USA.
    Karamichos, Dimitrios
    University of Oklahoma, OK USA.
    Utheim, Tor P.
    Harvard Medical Sch, MA USA; University of Oslo, Norway; Vestre Viken Hospital Trust, Norway; University of Coll Southeast Norway, Norway.
    Islam, Rakibul
    Harvard Medical Sch, MA USA; University of Oslo, Norway.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Islam, Mohammad Mirazul Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Hodges, Robin R.
    Harvard Medical Sch, MA USA.
    Wnek, Gary E.
    Case Western Reserve University, OH 44106 USA.
    Kaplan, David L.
    Tufts University, MA 02155 USA.
    Dartt, Darlene A.
    Harvard Medical Sch, MA USA.
    Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 14, s. 6134-6146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.

  • 4.
    Islam, Mohammad M.
    et al.
    Swedish Medical Nanoscience Center, Karolinska Institutet, Stockholm, Sweden.
    Cėpla, Vytautas
    Center for Physical Sciences and Technology, Vilnius, Lithuania.
    He, Chaoliang
    Ottawa Hospital Research Institute, Ontario, Canada.
    Edin, Joel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rakickas, Tomas
    Center for Physical Sciences and Technology, Vilnius, Lithuania.
    Kobuch, Karin
    Technische Universität München, Germany.
    Ruželė, Živilė
    Center for Physical Sciences and Technology, Vilnius, Lithuania.
    Jackson, Bruce W.
    Ottawa Hospital Research Institute, Ontario, Canada.
    Rafat, Mehrdad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute, Ontario, Canada.
    Lohmann, Chris P.
    Technische Universität München, Germany.
    Valiokas, Ramūnas
    Center for Physical Sciences and Technology, Vilnius, Lithuania.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Swedish Medical Nanoscience Center, Karolinska Institutet, Stockholm, Sweden; Ottawa Hospital Research Institute, Ontario, Canada.
    Functional fabrication of recombinant human collagen–phosphorylcholine hydrogels for regenerative medicine applications2015Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 12, s. 70-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes of the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500 μm thick RHCIII-MPC constructs comprising over 85% water, are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, as compared to the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30 μm wide fibronectin stripes enhanced cell attachment and showed highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas.

  • 5.
    Islam, Mohammad Mirazul
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Harvard Medical School, Boston, MA USA.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, Ukraine.
    Reddy, Jagadesh C
    Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad, India.
    Pasyechnikova, Nataliya
    Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, Ukraine.
    Alarcon, Emilio I
    Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON Canada.
    Hayes, Sally
    School of Optometry and Vision Sciences College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 7Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, UK.
    Lewis, Philip
    School of Optometry and Vision Sciences College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 7Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, UK.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    He, Chaoliang
    Key Laboratory of Polymer Eco-materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
    Iakymenko, Stanislav
    Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, Ukraine.
    Liu, Wenguang
    School of Materials Science and Engineering, Tianjin University, Tianjin, China.
    Meek, Keith M
    School of Optometry and Vision Sciences College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK; 7Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, UK.
    Sangwan, Virender S
    Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad, India.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Montreal, Montreal, Canada.
    Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation2018Ingår i: NPJ Regenerative medicine, ISSN 2057-3995, Vol. 3, artikel-id 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1-2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to near normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal tissue and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients.

  • 6.
    Islam, Mohammad Mirazul
    et al.
    Swedish Medical Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Merrett, Kimberley
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fabrication of a human recombinant collagen-based corneal substitute using carbodiimide chemistry2013Ingår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1014, s. 157-164Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human recombinant collagen can be cross-linked with a variety of chemical cross-linking agents. Cross-linking methods can be tuned to confer collagen-based scaffolds with specific physical properties, improved antigenicity and thermal stability without impeding the ability of the material to integrate into the surrounding tissue and to promote regeneration. Here, we describe a method to cross-link human recombinant collagen using a water soluble carbodiimide. Carbodiimides are referred to as zero-length cross-linking agents as they are not incorporated into the final cross-link and thus pose minimal risk with respect to cytotoxicity. The resulting collagen-based scaffold possesses properties comparable to that of the human cornea and is thus suitable for use as a corneal substitute.

  • 7.
    Islam, Mohammad Mirazul
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Ravichandran, Ranjithkumar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Olsen, D.
    FibroGen Inc, CA 94158 USA.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation2016Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, nr 61, s. 55745-55749Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas.

  • 8.
    Jangamreddy, Jaganmohan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. LV Prasad Eye Inst, India.
    Haagdorens, Michel K. C.
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lewis, Philip
    Cardiff Univ, Wales.
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Alarcon, Emilio I.
    Univ Ottawa, Canada.
    Zakaria, Nadia
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Meek, Keith M.
    Cardiff Univ, Wales.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Correction: Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants (vol 69, pg 120, 2018)2018Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 81, s. 330-331Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 9.
    Jangamreddy, Jaganmohan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. LV Prasad Eye Inst, India.
    Haagdorens, Michel K. C.
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lewis, Philip
    Cardiff Univ, Wales.
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Alarcon, Emilio I.
    Univ Ottawa, Canada.
    Zakaria, Nadia
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Meek, Keith M.
    Cardiff Univ, Wales.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants2018Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 69, s. 120-130Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a pre- clinicalmini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues. Statement of significance Although biomaterials comprising full-length recombinant human collagen and extracted animal collagen have been evaluated and used clinically, these macromolecules provide only a limited number of functional groups amenable to chemical modification or crosslinking and are demanding to process. Synthetic, customizable analogs that are functionally equivalent, and can be readily scaled-up are therefore very desirable for pre-clinical to clinical translation. Here, we demonstrate, using cornea regeneration as our test bed, that collagen-like-peptides conjugated to multifunctional polyethylene glycol (CLP-PEG) when grafted into mini-pigs as corneal implants were functionally equivalent to recombinant human collagen-based implants that were successfully tested in patients. We also show for the first time that these materials affected regeneration through stimulation of extracellular vesicle production by endogenous host cells that have migrated into the CLP-PEG scaffolds. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd.

  • 10.
    Jangamreddy, Jaganmohan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Haagdorens, Michel K. C.
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lewis, Philip
    Cardiff Univ, Wales.
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Alarcon, Emilio I.
    Univ Ottawa Heart Inst, Canada.
    Zakaria, Nadia
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Meek, Keith M.
    Univ Ottawa Heart Inst, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants (vol 69, pg 120, 2018)2019Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 88, s. 556-557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 11.
    Koh, Li Buay
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Swedish Nanoscience Center, Karolinska Institute, Stockholm , Sweden .
    Mitra, Debbie
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Noel, Christopher
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Merett, Kimberley
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Odorcic, Silvia
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Jackson, William Bruce
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Liedberg, Bo
    Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Swedish Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes2013Ingår i: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 4, nr 3, s. 162-177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A bi-functional epoxy-based cross-linker, 1,4-Butanediol diglycidyl ether (BDDGE), was investigated in the fabrication of collagen based corneal substitutes. Two synthetic strategies were explored in the preparation of the cross-linked collagen scaffolds. The lysine residues of Type 1 porcine collagen were directly cross-linked using l,4-Butanediol diglycidyl ether (BDDGE) under basic conditions at pH 11. Alternatively, under conventional methodology, using both BDDGE and 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as cross-linkers, hydrogels were fabricated under acidic conditions. In this latter strategy, Cu(BF4)2·XH2O was used to catalyze the formation of secondary amine bonds. To date, we have demonstrated that both methods of chemical cross-linking improved the elasticity and tensile strength of the collagen implants. Differential scanning calorimetry and biocompatibility studies indicate comparable, and in some cases, enhanced properties compared to that of the EDC/NHS controls. In vitro studies showed that human corneal epithelial cells and neuronal progenitor cell lines proliferated on these hydrogels. In addition, improvement of cell proliferation on the surfaces of the materials was observed when neurite promoting laminin epitope, IKVAV, and adhesion peptide, YIGSR, were incorporated. However, the elasticity decreased with peptide incorporation and will require further optimization. Nevertheless, we have shown that epoxy cross-linkers should be further explored in the fabrication of collagen-based hydrogels, as alternatives to or in conjunction with carbodiimide cross-linkers.

  • 12.
    Lee, Chyan-Jang
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Buznyk, Oleksiy
    Filatov Institute of Eye Diseases and Tissue Therapy, Odessa, Ukraine .
    Kuffova, Lucia
    University of Aberdeen, Scotland .
    Rajendran, Vijayalakshmi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. University of Aberdeen, Scotland.
    Forrester, John V.
    University of Aberdeen, Scotland.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Skog, Mårten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ahlqvist, Jenny
    Vironova AB, Stockholm, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy2014Ingår i: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, nr 3, s. 1-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To evaluate the potential utility of collagen-based corneal implants with anti?Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37. Methods: We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined. Results: Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size. Conclusion: LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti?HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses. Translational Relevance: LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.

  • 13.
    Moelzer, Christine
    et al.
    Univ Aberdeen, Scotland.
    Shankar, Sucharita P.
    Univ Aberdeen, Scotland; UCB Pharma, England.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Harvard Med Sch, MA 02115 USA; Harvard Med Sch, MA 02115 USA.
    Forrester, John V
    Univ Aberdeen, Scotland.
    Kuffova, Lucia
    Univ Aberdeen, Scotland.
    Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition2019Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen-containing matrices, Matrigel(TM) and de-cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a "tolerogenic" phenotype. The same applied to singly crosslinked CMP-PEG gels. RHCIII gels singly crosslinked using either N-(3-dimethylaminopropyl)-N -ethylcarbodiimide with the coinitiator N-hydroxy succinimide (EDC-NHS) or N-cyclohexyl-N-(2-morpholinoethyl)carbodiimide metho-p-toulenesulfonate with NHS (CMC-NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2-methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte-associated immunoglobulin-like receptor-1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.

  • 14.
    Patra, Hirak Kumar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Department of Chemical Engineering and Biotechnology, Cambridge University, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK.
    Azharuddin, Mohammad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Massachusetts Eye and Ear and Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, USA.
    Papapavlou, Georgia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Deb, Suryyani
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Department of Biochemistry, University of Calcutta, Calcutta, India; Department of Biotechnology, Maulana Abul Kalam Azad University of Technology (MAKAUT), West Bengal, India.
    Osterrieth, Johannes
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Zhu, Geyunjian Harry
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Romu, Thobias
    Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dhara, Ashis K.
    Centre for Image Analysis, Uppsala University, Uppsala, Sweden; Department of Electrical Engineering, National Institute of Technology Durgapur, West Bengal, India.
    Jafari, Mohammad Javad
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Gadheri, Amineh
    Department of Oncology‐Pathology, Karolinska Institute, Stockholm, Sweden.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Rajan, Madhavan S.
    Department of Ophthalmology, Cambridge University Hospitals NHS Trust and Vision and Eye Research Institute (VERI), Anglia Ruskin University, Cambridge, UK.
    Slater, Nigel K. H.
    Department of Chemical Engineering and Biotechnology, Cambridge University, Philippa Fawcett Drive, Cambridge, UK.
    Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants2019Ingår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, artikel-id 1903760Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory‐made artificial corneas is not fully realized in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other microbes, enzyme overexpression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment and counter the effects of inflammation or infection, which are able to track early signs of implant failure in situ. This work reports a nanotoolbox comprising tools for protection from infection, promotion of regeneration, and noninvasive monitoring of the in situ corneal environment. These nanosystems can be incorporated within pro‐regenerative biosynthetic implants, transforming them into theranostic devices, which are able to respond to biological changes following implantation.

    Publikationen är tillgänglig i fulltext från 2020-07-15 00:01
  • 15.
    Patra, Hirak Kumar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Sharma, Yashpal
    International Center for Materials Nanoarchitectonics, National Institute for Materials Science (NIMS), Sengen, Tsukuba, Ibaraki, Japan .
    Islam, Mohammad Mirazul
    Swedish Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Jafari, Mohammad Javad
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Arul Murugan, N.
    Virtual Laboratory for Molecular Probes, Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology (KTH), Stockholm, Sweden .
    Kobayashi, Hisatoshi
    International Center for Materials Nanoarchitectonics, National Institute for Materials Science (NIMS), Sengen, Tsukuba, Ibaraki, Japan .
    Turner, Anthony
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Tiwari, Ashutosh
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten. International Center for Materials Nanoarchitectonics, National Institute for Materials Science (NIMS), Sengen, Tsukuba, Ibaraki, Japan ; Tekidag AB, UCS, Linköping, Sweden; Vinoba Bhave Research Institute, Saidabad, Allahabad, India .
    Inflammation-sensitive in situ smart scaffolding for regenerative medicine2016Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, nr 39, s. 17213-17222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To cope with the rapid evolution of the tissue engineering field, it is now essential to incorporate the use of on-site responsive scaffolds. Therefore, it is of utmost importance to find new Intelligent biomaterials that can respond to the physicochemical changes in the microenvironment. In this present report, we have developed biocompatible stimuli responsive polyaniline-multiwalled carbon nanotube/poly(N-isopropylacrylamide), (PANI-MWCNT/PNIPAm) composite nanofiber networks and demonstrated the physiological temperature coordinated cell grafting phenomenon on its surface. The composite nanofibers were prepared by a two-step process initiated with an assisted in situ polymerization followed by electro-spinning. To obtain a smooth surface in individual nanofibers with the thinnest diameter, the component ratios and electrospinning conditions were optimized. The temperature-gated rearrangements of the molecular structure are characterized by FTIR spectroscopy with simultaneous macromolecular architecture changes reflected on the surface morphology, average diameter and pore size as determined by scanning electron microscopy. The stimuli responsiveness of the nanofibers has first been optimized with computational modeling of temperature sensitive components (coil-like and globular conformations) to tune the mechanism for temperature dependent interaction during in situ scaffolding with the cell membrane. The nanofiber networks show excellent biocompatibility, tested with fibroblasts and also show excellent sensitivity to inflammation to combat loco-regional acidosis that delay the wound healing process by an in vitro model that has been developed for testing the proposed responsiveness of the composite nanofiber networks. Cellular adhesion and detachment are regulated through physiological temperature and show normal proliferation of the grafted cells on the composite nanofibers. Thus, we report for the first time, the development of physiological temperature gated inflammation-sensitive smart biomaterials for advanced tissue regeneration and regenerative medicine.

  • 16.
    Polisetti, Naresh
    et al.
    University of Erlangen-Nürnberg, Erlangen, Germany.
    Islam, Mohammad Mirazul
    Swedish Medical Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Griffith, May
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi.
    The artificial cornea2013Ingår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1014, s. 45-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human corneal transplantation to date suffers from the shortage of good-quality donor tissue, and in some conditions, allografting is contraindicated. A range of artificial replacements to donor allograft corneas have been developed. These range from keratoprostheses (KPro) that replace basic corneal functions of light transmission and protection to regenerative medicine strategies for regenerating one or more layers of the human cornea. This chapter reviews the advances made in developing artificial corneas or more accurately, artificial alternatives to donor allograft corneas for ocular application.

  • 17.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Koh, Li Buay
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Highly elastic epoxycross‐linked collagen hydrogels for corneal tissueengineering2012Ingår i: Acta Ophthalmologica; Special Issue: Abstracts from the 2012 European Association for Vision and Eye Research Conference, Volume 90, Issue Supplement s249, page 0, September 2012, John Wiley & Sons, 2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    Purpose Our objective is to develop novel materials that support the regeneration of diseased or damaged corneas. Despite the promising clinical results that we previously reported on biosynthetic corneas, more robust and elastic materials are required to withstand the adverse host conditions faced for high risk transplantation in severely damaged or diseased corneas. This presentation will provide details on an epoxy cross-linked collagen-based scaffold with enhanced mechanical properties.

    Methods We have developed a range of collagen-based materials as mimics of the cell-free corneal stromal extracellular matrix. In this study, cross-linked polymer networks of collagen hydrogels were prepared using a hybrid of 1,4-butanediol diglycidyl ether (BDDGE) and carbodiimides (e.g. EDC-NHS) as cross-linkers. Briefly, 10w/w% porcine collagen type I was mixed in a T-piece system at various compositions and pH, e.g. pH 5, pH 11, and incorporated with laminin adhesive peptides (YIGSR, and IKVAV). Promising material formulations were tested for their physiochemical properties (e.g. mechanical, optical, water uptake, FTIR, and thermal degradation) and physiological properties (e.g. interactions with corneal cells, and biodegradation).

    Results The hybrid BDDGE hydrogels demonstrated improved mechanical properties and degree of cross-linking while maintaining their optical clarity and biocompatibility compared to controls (e.g. EDC/NHS-crosslinked hydrogels). Incorporation of laminin-derived cell-adhesive peptide (IKVAV) demonstrated significant increase in corneal cells (HCECs) proliferation compared to controls.

    Conclusion The hybrid BDDGE-crosslinked collagen-based hydrogels have the potential for use as tissue-engineered corneal substitutes.

  • 18.
    Wickham, Abeni M.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Karolinska Institutet, Stockholm, Sweden.
    Mondal, Debasish
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Sadhu, Veera
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Tamás, Éva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Polisetti, Naresh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Richter-Dahlfors, Agneta
    Karolinska Institutet, Stockholm, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan. Nanyang Technological University, Singapore.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Karolinska Institutet, Stockholm, Sweden.
    Polycaprolactone–thiophene-conjugated carbon nanotube meshes as scaffolds for cardiac progenitor cells2014Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, nr 7, s. 1553-1561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, while allowing regeneration by incorporated cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as both sheets by solvent casting, and fibrous meshes by electrospinning, as potential patches, to determine the role of topology in proliferation and phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs) were incorporated to enhance the mechanical strength. We showed that freshly isolated CPCs from murine hearts neither attached nor spread on the PCL sheets, both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T-CNT supported CPC adhesion, proliferation, and differentiation. The incorporation of T-CNT into PCL resulted in a significant increase in mechanical strength but no morphological changes to the meshes. In turn, proliferation, but not differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing meshes. We have shown that changing the topology of PCL, a known hydrophobic material, dramatically altered its properties, in this case, allowing CPCs to survive and differentiate. With further development, PCL/T-CNT meshes or similar patches may become a viable strategy to aid restoration of the postmyocardial infarction myocardium.

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