Polycaprolactone and polycaprolactone/chitosan nanofibres functionalised with the pH-sensitive dye Nitrazine Yellow

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Understanding the properties of biologically active glassy materials for tissue engineering through modelling and experiment

Bioactive glasses (BGs) are amorphous materials exhibiting biocompatibility properties,gaining great interest as biomaterials for regenerative medicine. This work comprises twoparts. First, the bioactivity properties that fluoridated phosphate-based bioactive glasses(F-PBGs) exhibit once implanted, for dental repair applications, was studied. Second,the experimental design of cardiac patches, containing 45S5 bioactive glasses for cardiactissue engineering, was undertaken. [Continues.

The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation

Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds.Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress–strain data of the scaffolds at various stages of degradation.During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02±0.23 MPa to 0.38±0.004 MPa and from 46±11% to 12±2%, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071±0.016 MPa to 0.010±0.007 MPa and from 69±24% to 8±2%, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r2>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation

Rotary Jet Spinning of Polymer Fibres

Polymeric nanofibres can be produced from a variety of methods such as electrospinning and melt blowing, with fibres being produced having applications in many sectors such as biomedicine, composites and filtration. Existing methods are not however capable of producing nanofibres to commercial volumes in an energy efficient way. In this research we investigate a new method of producing nanofibres, namely Rotary Jet Spinning (RJS), which is a relatively new method of fibre production similar to candyfloss production, where centrifugal forces are used to expel jets of polymer from a state of melt or solution in order to produce polymeric fibres. We investigate this method in detail, initially concentrating on the comparison between electrospinning and RJS. Firstly, it was found that electrospinning produced slightly smaller fibre diameters compared to RJS over a broader range of solution concentrations. Secondly, the ability to produce high modulus fibres was investigated by means of an imidization technique, where polyamic acid solution was produced and spun into fibres before conversion to a co-polyimide fibre with an elastic modulus of around 40 GPa. In the third experimental chapter, the viscosity reliability of the RJS process was evaluated by means of computational fluid dynamics simulations, where it was shown that low viscosity (1-10 Pa.s) Newtonian fluids are required to establish fibre production. For fluids with lower viscosities, beading occurred in solution spinning and droplets were produced from melt spinning. Viscosities higher than the recommended value resulted in blockage, with no fibres being produced from either method. Lastly, the production of ceramic fibres was evaluated to establish the ability of the RJS process to produce a ceramic nanofibre. Fibres on the nanoscale were not achieved, however a variation in solvent volatility and crosslinking time were factors in fibre diameter reduction, with solvent variations highlighting the potential of this process to achieve the required fibre size from RJS and thereby demonstrating this technology as a viable option for high volume fibre production.EPSRC grant number 150219

Evaluation of Electrospun Nanofibrous Structures for Drug Release Application

Biopolymers show the excellent biodegradability and efficient release sustainability for encapsulated drugs. In particular, electrospun polymer or composite fibre mats provide greater benefits owing to their competitive release properties and large specific surface area. This research work focused on electrospun nanofibres derived from poly(e-caprolactone) (PCL), poly(lactic acid) (PLA) and PCL/ magnetic nanoparticles (MPs) solutions by carrying a therapeutic compound tetracycline hydrochloride (TCH) with the potential use for medical applications. The material systems were examined to evaluate how composite constituents affected the surface morphology with the aim of drug release control. It has been found that the fibre diameter decreased considerably with the addition of TCH drug. The average fibre diameter was also reduced with additional MPs due to enhanced solution conductivity. Furthermore, Fourier transform infrared spectroscopy (FTIR) proved the successful encapsulation of TCH drug. Over short-term periods, the TCH release from PCL nanofibres was higher than PCL/ MPs and PLA nanofibres; whereas, on a long-term run, TCH release from PCL became slower owing to its high degree of crystallinity. The TCH release kinetics of PCL/ TCH nanofibres were better estimated by Zeng model when compared with PLA/TCH counterparts

Polymer- and Hybrid-Based Biomaterials for Interstitial, Connective, Vascular, Nerve, Visceral and Musculoskeletal Tissue Engineering

In this review, materials based on polymers and hybrids possessing both organic and inorganic contents for repairing or facilitating cell growth in tissue engineering are discussed. Pure polymer based biomaterials are predominantly used to target soft tissues. Stipulated by possibilities of tuning the composition and concentration of their inorganic content, hybrid materials allow to mimic properties of various types of harder tissues. That leads to the concept of “one-matches-all” referring to materials possessing the same polymeric base, but different inorganic content to enable tissue growth and repair, proliferation of cells, and the formation of the ECM (extra cellular matrix). Furthermore, adding drug delivery carriers to coatings and scaffolds designed with such materials brings additional functionality by encapsulating active molecules, antibacterial agents, and growth factors. We discuss here materials and methods of their assembly from a general perspective together with their applications in various tissue engineering sub-areas: interstitial, connective, vascular, nervous, visceral and musculoskeletal tissues. The overall aims of this review are two-fold: (a) to describe the needs and opportunities in the field of bio-medicine, which should be useful for material scientists, and (b) to present capabilities and resources available in the area of materials, which should be of interest for biologists and medical doctors.</jats:p

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

Uudsete antibakteriaalsete haavakatete valmistamine kasutades elektrospinnimise tehnoloogiat

Väitekirja elektrooniline versioon ei sisalda publikatsiooneTõusvate kulude ning aina keerulisemate ravijuhtude tõttu on halvasti paranevad kroonilised haavandid muutunud kaasaegses ühiskonnas väga suureks probleemiks. Haavadega kaasneb alati infektsioonioht, seetõttu näeb kaasaegne haavaravi ette, et taastatakse haava homeöstaas ning hoitakse kontrolli all bakterite arvukus. Kõige probleemsemaks osutuvad kaasuvate haigustega patsientidid (näiteks diabeedihaiged), kelle häirunud immuunvastus võib takistada ravi efektiivsust ning pikendada ravi kestvust. Infektsioosse haavandi raviskeemis on antibiootikumide manustamine väga olulisel kohal. Lokaalne antibakteriaalne haavaravi (kasutades enamlevinud traditsioonilisi ravimvorme) on väga levinud, kuid selle efektiivsus on siiani küsitav ravimi lühikese toimeaja ja pideva manustamise tõttu. Seetõttu on kaasaegne ravimvormide teadustöö keskendunud just kohaspetsiifiliste lokaalsete antibakteriaalsete ravimkandursüsteemide väljatöötamisele, mis omaksid veel täiendavat funktsionaalsust (haava paranemise toetamine). Elektrospinnimine (ES) on lihtne ja laialtlevinud meetod polümeersete fiibermaatriksite tootmiseks, millele iseloomulikeks omadusteks on: kontrollitav morfoloogia, suur eripind ning poorsus. Lisaks on maatriksitesse võimalik lihtsa vaevaga inkorporeerida erinevaid raviaineid, mis võimaldab neid kasutada ravimkandursüsteemidena. ES fiibermaatriksid sobivad ideaalselt haavakateteks: omades nahale omase rakuvälise maatriksiga sarnast struktuuri, mis annab neile hea haavaeksüdaadi absorbeerimise võime ning tagab gaasi – ja ainevahetuse haavas. Maatriksite mehaanilised omadused on muudetavad vastavalt vajadusele – lihtsustamaks kasutust ning tagamaks soodsat keskkonda rakkudele, mis vastutavad haavade paranemise eest. Antibakteriaalsete haavakatete väljatöötamisel on oluline uurida nende mõju bakterirakkudele. Haavakate peaks inhibeerima bakterite arvukuse tõusu haavas ning kaitsma haava kontaminatsiooni eest. Käesolevas töös valmistati ES teel antibakteriaalsete omadustega fiibermaatrikseid, mida saaks kasutada lokaalseks haavaraviks. Leiti, et poorseid fiibreid sisaldavate maatriksite valmistamiseks oli oluline sobivate lahustite ning keskkonnaparameetrite valik. Maisivalgul baseeruvate fiibermaatriksite valmistamiseks osutus sobivaimaks koaksiaalse ES ning abiainete kasutamine. Kasutatud lahustid ja abiained mõjutasid fiibermaatriksite morfoloogiat, struktuuri, mehhaanilisi omadusi ning raviaine vabanemise kiirust. Maatriksite ehitus mõjutas oluliselt elusrakkude (bakteri- ning eükarüootsete rakkude) käitumist maatriksitel. Leiti, et poorseid fiibreid sisaldav maatriks soodustas fibroblastide kinnitumist ning kasvu, ja omas ka kõige suuremat E. coli biokile vastast toimet. Maisivalgul baseeruvatel fiibermaatriksitel oli fibroblastide kasv ning kinnitumine väiksem võrreldes polükaprolaktooni sisaldava fiibermaatriksiga.Wound treatment is a worldwide problem with annually increasing costs and insufficient treatment options. There is always contamination related to wounds which increases the risk for the development of infection. Therefore the main treatment strategy has been to restore the homeostasis at the wound site as well as control the bacterial load. The problem arises when the patient's medical condition (for example diabetes) inhibits the native immune response causing failed and long-lasting treatment. The administration of antibacterial drugs is a vital part of chronic wound and infection treatment strategy. Topical treatment with antibiotics (conventional drug formulations such as gels, creams) is frequently used but its efficiency is still uncertain. Therefore novel drug delivery research is focused on finding the site-specific drug delivery systems (DDS) with enhanced antibacterial properties. Electrospinning (ES) is a straightforward method for the production of polymeric fibers with specific features: controlled surface morphology, large specific surface area, tunable porosity and relatively simple incorporation of drugs giving them potential to be used as DDS. ES scaffolds have potential in wound healing due to having structure similar to the extracellular matrix, which offers superior absorption of the wound exudate as well as enhanced gas exchange properties. Furthermore, the scaffolds have suitable mechanical properties which can be designed to ease application and offer suitable surface for cell growth in charge of native wound healing. When developing antibacterial scaffold for wound infection treatment the bacterial/scaffold interactions have to be addressed. Ideally the scaffold should inhibit the bacterial growth at the wound site and protect the wound from further contamination. In the present thesis ES was used to prepare antibacterial fiber scaffolds for wound healing applications. It was seen that the combination of suitable solvent systems, and environmental parameters were vital in order to produce antibacterial drug containing polymer based fibers with surface porosity. The solvent systems had an effect on the morphology, structure, mechanical and drug release properties of the scaffolds. The structural differences also affected the behaviour of cells (bacterial and eukaryotic) on scaffolds . Fibers with surface porosity supported fibroblast attachment and growth as well as provided the best antibiofilm activity against E. coli. Another part of the thesis was to develop zein based antibacterial fiber scaffolds. Coaxial ES method together with plasticisers were used in order to develop zein-based core-shell structured scaffolds. The scaffolds were also characterised and differences were seen compared to the polycaprolactone-based scaffolds.https://www.ester.ee/record=b552587