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  • 1.
    Cardemil, Carina
    et al.
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden .
    Elgali, Ibrahim
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Xia, Wei
    Applied Materials Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Emanuelsson, Lena
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Norlindh, Birgitta
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Omar, Omar
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
    Thomsen, Peter
    Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden .
    Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e84932Article in journal (Refereed)
    Abstract [en]

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

  • 2.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy2012In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, no 4, p. 047004-Article in journal (Refereed)
    Abstract [en]

    Model based data analysis of diffuse reflectance spectroscopy data enables the estimation of optical and structural tissue parameters. The aim of this study was to present an inverse Monte Carlo method based on spectra from two source-detector distances (0.4 and 1.2 mm), using a multilayered tissue model. The tissue model variables include geometrical properties, light scattering properties, tissue chromophores such as melanin and hemoglobin, oxygen saturation and average vessel diameter. The method utilizes a small set of presimulated Monte Carlo data for combinations of different levels of epidermal thickness and tissue scattering. The path length distributions in the different layers are stored and the effect of the other parameters is added in the post-processing. The accuracy of the method was evaluated using Monte Carlo simulations of tissue-like models containing discrete blood vessels, evaluating blood tissue fraction and oxygenation. It was also compared to a homogeneous model. The multilayer model performed better than the homogeneous model and all tissue parameters significantly improved spectral fitting. Recorded in vivo spectra were fitted well at both distances, which we previously found was not possible with a homogeneous model. No absolute intensity calibration is needed and the algorithm is fast enough for real-time processing.

  • 3.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Zhang, Jiabin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Los, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Electroactive polymer scaffolds for cardiac tissue engineering2015In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper (Refereed)
    Abstract [en]

    By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  • 4.
    Holmberg, L. Joakim
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Management and Engineering, Mechanics.
    Lund Ohlsson, Marie
    Linköping University, The Institute of Technology. Linköping University, Department of Management and Engineering, Mechanics.
    Danvind, Jonas
    Mittuniversitetet.
    Can Simulations Assist in Classification Development?2013In: Equipment and Technology in Paralympic Sports, International Paralympic Committee , 2013Conference paper (Other academic)
    Abstract [en]

    There is a critical need for research that describes the extent to which impairments of varying type, severity and distribution impact performance in Paralympic sports. It is important with evidence-based judgment on how the impairments aect performance. In the following, we present a complementary evidence-based tool for classication.

    Let us start with an example. We recently presented a study (Holmberg et al., 2012)1 that utilized two full-body musculoskeletal simulation models of cross-country skiing (double-poling). The models were identical except that one carried no muscles in the right lower leg and foot; thus mimicking a lower leg prosthesis. It was hypothesized that a lower leg prosthesis would inuence muscular work throughout the whole body. Results showed that to generate the same motion and external work, an able-bodied skier only had to produce about 80% metabolic muscle work compared to a disabled skier (with a non-active right lower leg prosthesis).

    In reality there is always psychological factors present and it is probably not possible to nd two human beings (one fully functional and one impaired) with the same tness, size, strength and technique. Thus, it is hard to nd the unbiased eect of an impairment on performance in a speci c sport. The example above shows the strength of using simulations because a  musculoskeletal model yields quantitative data on the unbiased eect of dierent functional impairments.

    In cross-country skiing, athletes with functional impairments are, in 'competition format' classification, assigned to dierent categories with weight factors. Athletes perform their race and the result list is presented as race time multiplied by weight factor. In the future, musculoskeletal simulations may assist in answering how a specic functional impairment aects performance and thereby improve the fairness in assigning weight factors for classication.

  • 5.
    Jonsson, Amanda
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Song, Zhiyang
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Nilsson, David
    Acreo Swedish ICT AB, SE-601 17 Norrköping, Sweden.
    Meyerson, Björn A.
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Linderoth, Bengt
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Therapy using implanted organic bioelectronics2015In: Science Advances, ISSN 2375-2548, Vol. 1, no 4, article id e1500039Article in journal (Refereed)
    Abstract [en]

    Many drugs provide their therapeutic action only at specific sites in the body, but are administered in ways that cause the drug’s spread throughout the organism. This can lead to serious side effects. Local delivery from an implanted device may avoid these issues, especially if the delivery rate can be tuned according to the need of the patient. We turned to electronically and ionically conducting polymers to design a device that could be implanted and used for local electrically controlled delivery of therapeutics. The conducting polymers in our device allow electronic pulses to be transduced into biological signals, in the form of ionic and molecular fluxes, which provide a way of interfacing biology with electronics. Devices based on conducting polymers and polyelectrolytes have been demonstrated in controlled substance delivery to neural tissue, biosensing, and neural recording and stimulation. While providing proof of principle of bioelectronic integration, such demonstrations have been performed in vitro or in anesthetized animals. Here, we demonstrate the efficacy of an implantable organic electronic delivery device for the treatment of neuropathic pain in an animal model. Devices were implanted onto the spinal cord of rats, and 2 days after implantation, local delivery of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was initiated. Highly localized delivery resulted in a significant decrease in pain response with low dosage and no observable side effects. This demonstration of organic bioelectronics-based therapy in awake animals illustrates a viable alternative to existing pain treatments, paving the way for future implantable bioelectronic therapeutics. Keywords

  • 6.
    Karimian, Najmeh
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology. Ferdowsi University of Mashhad, Mashhad, Iran.
    Turner, Anthony P.F.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Electrochemical evaluation of troponin T imprinted polymer receptor2014In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 59, p. 160-165Article in journal (Refereed)
    Abstract [en]

    The selective detection and quantification of macromolecular targets is a fundamental biological mechanism in nature. Molecularly imprinted polymers (MIPs) have been identified as one of the most promising synthetic alternatives to bioreceptors. However, expanding this methodology towards selective recognition of bulky templates such as proteins appears to be extremely challenging due to problems associated with removal of the template from the polymeric network. In this study, polymer imprinted with troponin T (TnT) was assessed using electrochemical methods and the influence of various extraction methods, including conventional immersion extraction, thermal annealing and ultrasonic-assisted extraction, on the binding characteristics of the troponin-to-imprinted polymer receptor was elucidated. Cyclic voltammetric deposition of o-phenylenediamine (o-PD) film in the presence of TnT as a template was performed in acetate buffer (0.5 M, pH 5.2) on a gold substrate. Solvent extraction of the target molecule was optimised and followed by subsequent washing with water. The electrochemistry of a ferro/ferricyanide probe was used to characterise the TnT MIP receptor film. The incubation of the TnT MIP receptor-modified electrode with respect to TnT concentration resulted in a suppression of the ferro/ferricyanide redox current. The dissociation constant (KD) was calculated using a two-site model of template affinity for the TnT MIP receptor. The synthetic TnT MIP receptor had high affinity for TnT with a KD of 2.3×10−13 M.

  • 7.
    Krishna Tummala, Gopi
    et al.
    Uppsala University, Sweden.
    Joffre, Thomas
    Uppsala University, Sweden.
    Lopes, Viviana R.
    Uppsala University, Sweden.
    Liszka, Aneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Buznyk, Oleksiy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. NAMS Ukraine, Ukraine.
    Ferraz, Natalia
    Uppsala University, Sweden.
    Persson, Cecilia
    Uppsala University, Sweden.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Mihranyan, Albert
    Uppsala University, Sweden.
    Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications2016In: ACS BIOMATERIALS SCIENCE and ENGINEERING, ISSN 2373-9878, Vol. 2, no 11, p. 2072-2079Article in journal (Refereed)
    Abstract [en]

    A nanocellulose-reinforced poly(vinyl alcohol) hydrogel material of exceptionally high water content for ophthalmic applications is presented (amp;gt;90 wt %), which also features a hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with remarkable strain-dependent mechanical strength and thereby demonstrates hyperelastic, rubber-like mechanical properties. The observed unusual mechanical behavior is due to both high water content and the combination of relatively stiff cellulose nanowhiskers entangled in a soft polymer matrix of poly(vinyl alcohol) (PVA), thus mimicking the structural characteristics of the corneas main constituents, i.e., water and collagen.

  • 8.
    Ljungberg, Ida
    Linköping University, Department of Physics, Chemistry and Biology.
    Evaluation of an Ozone Cabinet for Disinfecting Medical Equipment2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The spreading of infection is a significant and well-known problem in all healthcare environments today. The most prevalentways that infection spreads are either by direct contact between two individuals where one has an infection, or with anintermediate person or object as an infection carrier. This thesis aims to evaluate a method that could operate to disinfect thetype of medical equipment which is not suited to be disinfected by the commercially existing methods.

    In keeping with the long term goal of preventing the spread of infection, this project evaluates an ozone cabinet according to itsantimicrobial properties and investigates if the cabinet is suited to work as a disinfectant for some chosen test objects. Theobjects were borrowed from different hospital institutions at Motala Lasarett and the antimicrobial effect was evaluatedaccording to the reduction of colony forming units (CFUs) of samples taken from the object's surfaces after the treatment.

    The results show that the ozone cabinet is not able to kill bacterial spores (Geobacillus stearothermophilus), but could be veryefficient at killing living bacteria. Concentration setting 4 (56 ppm) in combination with a treatment period of at least 40minutes proves bacterial reductions varying between 83-98 %. Nevertheless, the sources of error are numerous and there is agreat variation between identical runs which indicates that more studies need to be performed in order to obtain clearer results.

  • 9.
    Mak, Wing Cheung
    et al.
    Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
    Georgieva, Radostina
    Berlin-Brandenburg Center of Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany.
    Renneberg, Reinhard
    Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
    Bäumler, Hans
    Berlin-Brandenburg Center of Regenerative Therapies, Charité-Universitätsmedizin Berlin, Germany.
    Protein particles formed by protein activation and spontaneous self-assembly2010In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 20, no 23, p. 4139-4144Article in journal (Refereed)
    Abstract [en]

    In this article, a non-chemical crosslinking method is used to produce pure protein microparticles with an innovative approach, so-called protein activation spontaneous and self-assembly (PASS). The fabrication of protein microparticles is based on the idea of using the internal disulfide bridges within protein molecules as molecular linkers to assemble protein molecules into a microparticle form. The assembly process is triggered by an activating reagent–dithiothreitol (DTT), which only involved in the intermediate step without being incorporated into the resulting protein microparticles. Conventional protein microparticle fabrication methods usually involve emulsification process and chemical crosslink reactions using amine reactive reagents such as glutaraldehdye or EDC/NHS. The resulting protein microparticles are usually having various size distributions. Most importantly crosslinking reactions using amine reactive reagents will result in producing protein microparticles with undesired properties such as auto-fluorescence and high toxicity. In contrast to the conventional methods, our technology provides a simple and robust method to produce highly homogeneous, stable and non-fluorescence pure protein microparticles under mild conditions at physiological pH and temperature. The protein microparticles are found to be biodegradable, non-toxic to MDCK cells and with preserved biological activities. Results on the cytotoxcity study and enzyme function demonstrate the potential applications of the protein microparticles in the area of pharmaceutics and analytical chemistry.

  • 10.
    Nworah, Nnamdi Felix
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Fabrication and Characterization of Individually Addressable Polypyrrole Trilayer Microactuators2012Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    Conjugated polymers are organic polymers that can conduct electricity. They undergo a volume change upon redox reaction and can be used as an active material in some micro- actuator system. Micro-actuators are useful in biomedical and electronic application. We have fabricated a patterned Polypyrrole (PPy) trilayer microactuator device that has individually addressable microactuators (a micro walker) which can operate in air. Furthermore, the PPy trilayer microactuator device is fabricated using standard microfabrication method called photolithography to pattern PPy on PVDF membrane material. An etching process was used to achieve the patterning process. We presented the result of characterization of speed as a function of voltage and thickness of PPy film. Secondly, distance as a function of applied voltage and thirdly, the work density as a function of applied voltage. The procedures for fabrication of PPy microactuator device, using clean room facility is detailed in this thesis.

  • 11.
    Rasmusson, Lars
    et al.
    Department Oral and Maxillofacial Surgery, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,.
    Abtahi, Jahan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit.
    Bisphosphonate associated osteonecrosis of the jaw: an update on pathophysiology, risk factors, and treatment.2014In: International Journal of Dentistry, ISSN 1687-8728, E-ISSN 1687-8736, article id 71035Article, review/survey (Refereed)
    Abstract [en]

    Osteonecrosis of the jaw in patients treated with bisphosphonates is a relatively rare but well known complication at maxillofacial units around the world. It has been speculated that the medication, especially long-term i.v. bisphosphonate treatment, could cause sterile necrosis of the jaws. The aim of this narrative review of the literature was to elaborate on the pathological mechanisms behind the condition and also to gather an update on incidence, risk factors, and treatment of bisphosphonate associated osteonecrosis of the jaw. In total, ninety-one articles were reviewed. All were published in internationally recognized journals with referee systems. We can conclude that necrotic lesions in the jaw seem to be following upon exposure of bone, for example, after tooth extractions, while other interventions like implant placement do not increase the risk of osteonecrosis. Since exposure to the bacterial environment in the oral cavity seems essential for the development of necrotic lesions, we believe that the condition is in fact chronic osteomyelitis and should be treated accordingly.

  • 12.
    Ravichandran, Ranjithkumar
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Extracellular matrix mimetic multi-functional scaffolds for tissue engineering and biomedical applications2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Regeneration of functional tissues or complex organs via the combination of viable cells, biomimetic scaffolds, morphogenic factors, and external biophysical cues are the principle aims of Tissue Engineering (TE). TE relies on the use of artificial 3D scaffolds that can mimic the microenvironment of native tissue to harness the regenerative potential of cells. The 3D scaffold provides an appropriate structural and functional support to foster the dynamic interplay of cells and signalling molecules to facilitate the formation of functional tissue. Taking inspiration from the multi-component and multi-functional role of native extracellular matrices (ECM), scaffold engineering provides a platform to understand and integrate the critical features from micro to macro scale necessary for repair and regeneration of tissues. Scaffold engineering also enables the interconnection of TE with its sub-disciplines such as drug delivery, in vitro disease modelling, biosensors or surgical science etc., by designing appropriate multi-functional scaffolds suitable for target specific applications.

    This thesis, addresses existing challenges to manipulate and customise ECM mimicking scaffolds and approaches to overcome these problems, by emphasising the importance of biomaterial design that can emulate the native ECM and potentially be tuned for tissue specific applications. Type I Collagen was functionalised with reactive methacrylate groups without altering its native triple helical structure. Methacrylated collagen (MAC) was further used as a functional building block to fabricate tuneable multifunctional scaffolds using bio-orthogonal thiol-Michael addition click chemistry by optimising several biophysical and biochemical parameters. This method provides the flexibility needed to fabricate injectable and implantable scaffolds based on the same functional components by tuning the modulus from Pa to kPa, thus rendering scaffolds suitable for use for either soft or hard tissues. The versatility of the scaffolds was evaluated by using it as pre-fabricated substrate for human corneal epithelial cells and as an injectable scaffold encapsulated with cardiac progenitor cells.

    The potential of MAC serving as a building block for engineering tailored made ECM mimetic scaffolds was further demonstrated by fabricating smart multi-functional stimuliresponsive scaffolds and conductive scaffolds using a free-radical co-polymerisation technique by choosing appropriate counterparts (polymers). The co-polymerisation of MAC and N-isopropyl acrylamide (NIPAm) formed an in situ, fast gellable, dual responsive (temp and pH) hydrogel comprising covalently linked networks of collagen and thermoresponsive NIPAm polymer. The multi-functionality of these hydrogels was demonstrated as an in-situ depot-forming tunable delivery platform for proteins and small drugs and as a structural support for human skeletal muscle cells. Pyrrole as a monomer was co-polymerised with MAC resulting in MAC-polypyrrole conductive hydrogel scaffold. The utility of ECM mimetic injectable conductive hydrogel scaffold was explored as a long-term continuous glucose-monitoring sensor under physiological conditions.

    Further, to overcome several challenges of Collagen such as inconsistent batch-tobatch reproducibility, risk of disease transmission, stability etc., a collagen-like-peptide (CLP) scaffold was designed as an alternative to collagen. This thesis demonstrates the use of Flexible Template Assisted Self-Assembly (TASS) of CLPs to mimic higher order collagen triple helical assembly by conjugating 38 amino acid length CLP with a multi-arm PEG maleimide template. 8-armPEG conjugated CLP (PEG-CLP) was used to fabricate robust hydrogel scaffolds using carbodiimide chemistry. The biocompatibility and potential of CLP scaffolds as an alternative to collagen was demonstrated by implanting it in mini pigs using corneal transplantation as a test bed. The bottom up-approach to assemble ECM mimetic functional peptides also allows us to design or manipulate CLPs with other bioactive motifs such as RGD or IKVAV to promote specific cell activities suitable for specific tissue regeneration.

    Overall, this thesis provides a modular platform to engineer multi-functional tunable ECM scaffolds based on type I Collagen and collagen-like peptides that combines multiple structural and bio-functional features for wide range of tissue engineering applications.

    List of papers
    1. Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications
    Open this publication in new window or tab >>Intelligent ECM mimetic injectable scaffolds based on functional collagen building blocks for tissue engineering and biomedical applications
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    2017 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 34, p. 21068-21078Article in journal (Refereed) Published
    Abstract [en]

    Hydrogels comprising natural extracellular matrix (ECM) components are very attractive as scaffolds for regenerative medicine applications due to their inherent biointeractive properties. Responsive materials that adapt to their surrounding environments and regulate transport of ions and bioactive molecules manifest significant advantages for biomedical applications. Although there are many exciting challenges, the opportunity to design, fabricate and engineer stimuli-responsive polymeric systems based on ECM components is particularly attractive for regenerative medicine. Here we describe a one-pot approach to fabricate in situ fast gellable intelligent ECM mimetic scaffolds, based on methacrylated collagen building blocks with mechanical properties that can be modulated in the kPa-MPa range and that are suitable for both soft and hard tissues. Physiochemical characterizations demonstrate their temperature and pH responsiveness, together with the structural and enzymatic resistance that make them suitable scaffolds for long-term use in regenerative medicine and biomedical applications. The multifunctionality of these hydrogels has been demonstrated as an in situ depot-forming delivery platform for the adjustable controlled release of proteins and small drug molecules under physiological conditions and as a structural support for adhesion, proliferation and metabolic activities of human cells. The results presented herein should be useful to the design and fabrication of tailor-made scaffolds with tunable properties that retain and exhibit sustained release of growth factors for promoting tissue regeneration.

    Place, publisher, year, edition, pages
    Royal Society of Chemistry, 2017
    National Category
    Other Chemistry Topics
    Identifiers
    urn:nbn:se:liu:diva-137627 (URN)10.1039/c7ra02927f (DOI)000399722300040 ()2-s2.0-85018519019 (Scopus ID)
    Note

    Funding Agencies|Swedish Research Council Junior Researcher Project [621-2012-4286]; CeNano PhD student salary grant; FP7-Health-Innovation program, acronym HESUB [2-2013-601700]

    Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-11-29Bibliographically approved
    2. Correction: Functionalised type-1 collagen as a hydrogel building block for bio-orthogonal tissue engineering applications (vol 4, pg 318, 2016)
    Open this publication in new window or tab >>Correction: Functionalised type-1 collagen as a hydrogel building block for bio-orthogonal tissue engineering applications (vol 4, pg 318, 2016)
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    2017 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 5, no 26, p. 5284-5284Article in journal (Other academic) Published
    Abstract [en]

    n/a

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2017
    National Category
    Physical Sciences Clinical Medicine Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-139559 (URN)10.1039/c7tb90075a (DOI)000404868400026 ()
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2018-04-10
    3. Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
    Open this publication in new window or tab >>Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
    Show others...
    2016 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, no 2, p. 318-326Article in journal (Refereed) Published
    Abstract [en]

    In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2016
    National Category
    Physical Sciences Chemical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-124491 (URN)10.1039/c5tb02035b (DOI)000367335200016 ()
    Note

    Funding Agencies|Swedish Research Council [621-2012-4286, 521-2012-5706]; NSERC; UOHI

    Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
    4. Applications of self-assembling peptide scaffolds in regenerative medicine: the way to the clinic
    Open this publication in new window or tab >>Applications of self-assembling peptide scaffolds in regenerative medicine: the way to the clinic
    2014 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 2, no 48, p. 8466-8478Article in journal (Refereed) Published
    Abstract [en]

    Peptides that self-assemble into well-defined nanofibrous networks provide a prominent alternative to traditional biomaterials for fabricating scaffolds for use in regenerative medicine and other biomedical applications. Such scaffolds can be generated by decorating a peptide backbone with other bioactives such as cell specific adhesion peptides, growth factors and enzyme cleavable sequences. They can be designed to mimic the three-dimensional (3D) structural features of native ECM and can therefore also provide insight into the ECM-cell interactions needed for development of scaffolds that can serve as regeneration templates for specific target tissues or organs. This review highlights the potential application of self-assembling peptides in regenerative medicine.

    Place, publisher, year, edition, pages
    Royal Society of Chemistry, 2014
    National Category
    Physical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-113073 (URN)10.1039/c4tb01095g (DOI)000345529400002 ()
    Note

    Funding Agencies|Swedish Research Council, Sweden [2012-42315-94008-81]

    Available from: 2015-01-09 Created: 2015-01-08 Last updated: 2017-12-05
    5. Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation
    Open this publication in new window or tab >>Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation
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    2016 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, no 61, p. 55745-55749Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    ROYAL SOC CHEMISTRY, 2016
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-130324 (URN)10.1039/c6ra08895c (DOI)000378275400008 ()
    Note

    Funding Agencies|Vinnova Indo-Sweden grant [2013-04645]; Integrative Regenerative Medicine Centre, Linkoping University (LiU); Region Ostergotland; Swedish Research Council grant [621-2012-4286]

    Available from: 2016-07-29 Created: 2016-07-28 Last updated: 2017-11-28
  • 13.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    State-of-the-art of stimuli-responsive materials2013In: Advanced Materials Letters, ISSN 0976-3961, E-ISSN 0976-397X, Vol. 4, no 7, p. 507-507Article in journal (Other academic)
  • 14.
    Tiwari, Ashutosh
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Sharma, Yashpal
    National Institute for Materials Science, Japan.
    Hattori, Shinya
    National Institute for Materials Science, Japan.
    Terada, Dohiko
    National Institute for Materials Science, Japan.
    Sharma, Ashok K.
    DCR University of Science and Technology, India.
    Turner, Anthony P. F.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Kobayashi, Hisatoshi
    National Institute for Materials Science, Japan.
    Influence of poly(N-isopropylacrylamide)-CNT-polyaniline three-dimensional electrospun microfabric scaffolds on cell growth and viability2013In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 99, no 5, p. 334-341Article in journal (Refereed)
    Abstract [en]

    This study investigates the effect on: 1) the bulk surface; and 2) the three-dimensional non-woven microfabric scaffolds of poly(N-isopropylacylamide)-CNT-polyaniline on growth and viability of  mice fibroblast cells L929. The poly(N-isopropylacylamide)-CNT-polyaniline was prepared using coupling chemistry and electrospinning was then used for the fabrication of responsive, nonwoven microfabric scaffolds. The electrospun microfabrics were assembled in regular three-dimensional scaffolds with OD: 400-500 mm; L: 6-20 cm. Mice fibroblast cells L929 were seeded on the both poly(N-isopropylacylamide)-CNT-polyaniline bulk surface as well as non-woven microfabric scaffolds. Excellent cell proliferation and viability was observed on poly(N-isopropylacylamide)-CNT-polyaniline non-woven microfabric matrices in compare to poly(N-isopropylacylamide)-CNT-polyaniline bulk and commercially available Matrigel™ even with a range of cell lines up to 168 h. Temperature dependent cells detachment behaviour was observed on the poly(N-isopropylacylamide)-CNT-polyaniline scaffolds by varying incubation at below lower critical solution temperature (LCST) of poly(N-isopropylacylamide). The results suggest that poly(N-isopropylacylamide)-CNT-polyaniline non-woven microfabrics could be used as a smart matrices for applications in tissue engineering.

  • 15.
    Wang, Hui
    et al.
    Anhui University, Peoples R China.
    Hu, Lei
    Anhui University, Peoples R China.
    Du, Wei
    Anhui University, Peoples R China.
    Tian, Xiaohe
    Anhui University, Peoples R China.
    Zhang, Qiong
    Anhui University, Peoples R China.
    Hu, Zhang-Jun
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Luo, Lei
    Southwest University, Peoples R China.
    Zhou, Hongping
    Anhui University, Peoples R China.
    Wu, Jieying
    Anhui University, Peoples R China.
    Tian, Yupeng
    Anhui University, Peoples R China; Nanjing University, Peoples R China.
    Two-Photon Active Organotin(IV) Carboxylate Complexes for Visualization of Anticancer Action2017In: ACS BIOMATERIALS SCIENCE and ENGINEERING, ISSN 2373-9878, Vol. 3, no 5, p. 836-842Article in journal (Refereed)
    Abstract [en]

    It is still a challenge that organotin(IV) carboxylate complexes with high-performance two-photon activity for cancer therapy. At present work, two novel organotin carboxylate complexes LSn1 and LSn2, containing coumarin moiety, were rationally designed for two-photon fluorescent imaging and anticancer purpose. The complexes possessed large two-photon action cross-sections and high quantum yields. Living cells evaluation revealed that complexes LSn1 and LSn2 exhibited good biocompatibility and deep tissue penetration over femtosecond laser with wavelength of 840 nm. Furthermore, the antitumor active and as well as possible mechanism of complexes LSn1 and LSn2 have been investigated systematically. The results indicated that complexes LSn1 and LSn2 could induce apoptotic cell death through a mitochondria] dysfunction and ROS elevation pathway. The present work provides a strategy for rationally designing organotin(IV) carboxylate complexes with two-photon activity and antitumor activity.

1 - 15 of 15
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