Applications of Silk in Biomedical and Healthcare Textiles

Global trends are shifting towards environmental friendly materials and manufacturing methods. Therefore, natural fiber applications are gaining traction globally. Silk, a natural protein fiber is one of the textile fibers that have recently received more attention due to the new frontiers brought about by technological advancement that has expanded the use of silk fiber beyond the conventional textile industry. The simple and versatile nature of silk fibroin process-ability has made silk appealing in wide range of applications. Silk is biocompatible, biodegradable, easy to functionalize and has excellent mechanical properties, in addition to optical transparency. This review chapter explores the use of silk in biomedical applications and healthcare textiles. Future trends in silk applications are also highlighted

Biomedical applications of nanofibrillar cellulose

Hydrogels are emerging as an important source for current biomaterial design, as they often possess intrinsic physical and mechanical similarities with soft tissue, are non-toxic and biocompatible. However, many hydrogel-based biomimetic materials are either derived from limited sources, or require external activators to achieve functionality, such as chemical crosslinking or environmental cues. Furthermore, many cross-linkers used with hydrogels are toxic, and environmental cues invoke slow responses. Therefore, to function as a rational biomaterial design for a biomedical application, these properties are preferably avoided, or improved with a composite system containing two or more polymer components to overcome these limitations. Plant-derived nanofibrillar cellulose (NFC) possesses the same intrinsic properties as many other hydrogels derived from the components of extracellular matrices (ECM). Therefore, NFC shares the biocompatibility and non-toxicity aspects of biomimetic materials. However, additional features of NFC can be exploited, such as shear-thinning properties, spontaneous self-gelation and chemical modification capabilities. Additionally, the source of NFC is practically inexhaustible, and is environmentally biodegradable, bearing no ecological burden. Therefore, when designing hydrogel-based biomaterials, NFC offers versatility, which enables the fabrication of potential biomedical applications for various purposes in an environmentally safe way. In this thesis, a wide range of potential applications of NFC-based hydrogels were investigated. These include 3D cell culturing, in vivo implantation and coating systems for drug and cell delivery, controlled drug delivery and local delivery as a bioadhesive system. These methods offer insight into the versatility of NFC-based hydrogels, which could improve the future design of biomaterials, for a safer and more efficient use in biomedical applications.Hydrogeelien käyttö uusien biomateriaalien lähteenä on jatkuvasti nousussa, koska niiden fysikaaliset ja mekaaniset ominaisuudet muistuttavat luontaisesti pehmytkudosta, ja ne ovat biologisesti yhteensopivia aiheuttamatta solutoksisuutta. Kuitenkin, monet hydrogeeleihin perustuvat biomimeettiset materiaalit ovat peräisin rajallisista lähteistä tai vaativat ulkoisia aktivaattoreita funktionaalisuuden takaamiseksi. Funktionaalisuus saavutetaan usein ympäristössä olevien tekijöiden avulla, kuten lämmön tai pH:n vaikutuksesta, tai kemiallisilla yhdisteillä. Monet hydrogeelejä aktivoivat kemialliset yhdisteet ovat kuitenkin solutoksisia, ja lisäksi, ympäristön kautta tapahtuva aktivointi on usein prosessina liian hidas. Tästä syystä, funktionaalisten biomateriaalien suunnittelussa näitä ominaisuuksia pyritään välttämään. Tai näitä ominaisuuksia pyritään korjaamaan yhdistämällä kahta tai useampaa polymeerikomponenttia samaan systeemiin. Kasviperäisellä nanofibrillaarisella selluloosalla (NFC) on samoja ominaispiirteitä kuin monilla muillakin hydrogeeleillä, jotka ovat peräisin ekstrasellulaarisesta matriisista. Tästä johtuen, NFC:llä on myös biomimeettisiä ominaisuuksia, kuten esimerkiksi biologinen yhteensopivuus ja myrkyttömyys. Näiden lisäksi, NFC:n muita ominaisuuksia voidaan hyödyntää, kuten leikkausohenevuutta, spontaania gelatinoitumista ja kemiallista muokattavuutta. Lisäksi NFC:n lähde raaka-aineena on käytännössä loputon ja se on ympäristössä biologisesti hajoava. Näistä syistä NFC on erittäin monipuolinen uusien biomateriaalien suunnittelussa. NFC:n avulla on mahdollista valmistaa potentiaalisia biolääketieteellisiä sovelluksia erilaisiin tarkoituksiin ympäristöystävällisellä tavalla. Tässä työssä tutkittiin NFC-pohjaisten hydrogeelien mahdollisia farmaseuttisia ja biolääketieteellisiä sovelluksia. Näitä sovelluksia ovat mm. 3D-soluviljely, in vivo implantaatio- ja päällystysmateriaali lääkeaineiden ja solujen kuljettamiseen elimistöön sekä kontrolloitu- ja paikallinen lääkeannostelu bioadhesiivisena lääkevalmisteena. Nämä menetelmät kartuttavat uutta tietoa liittyen NFC-pohjaisten hydrogeelien monipuolisuuteen. Lisäksi, näiden menetelmien avulla on mahdollista kehittää biomateriaalien suunnittelua kohti turvallisempaa ja tehokkaampaa biolääketieteellisten sovellusten käyttöä

Topographical and Biomechanical Guidance of Electrospun Fibers for Biomedical Applications

Electrospinning is gaining increasing interest in the biomedical field as an eco-friendly and economic technique for production of random and oriented polymeric fibers. The aim of this review was to give an overview of electrospinning potentialities in the production of fibers for biomedical applications with a focus on the possibility to combine biomechanical and topographical stimuli. In fact, selection of the polymer and the eventual surface modification of the fibers allow selection of the proper chemical/biological signal to be administered to the cells. Moreover, a proper design of fiber orientation, dimension, and topography can give the opportunity to drive cell growth also from a spatial standpoint. At this purpose, the review contains a first introduction on potentialities of electrospinning for the obtainment of random and oriented fibers both with synthetic and natural polymers. The biological phenomena which can be guided and promoted by fibers composition and topography are in depth investigated and discussed in the second section of the paper. Finally, the recent strategies developed in the scientific community for the realization of electrospun fibers and for their surface modification for biomedical application are presented and discussed in the last section

Electrospun membranes for implantable glucose biosensors

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityThe goal for this thesis was to apply electrospun biomimetic coatings on implantable glucose biosensors and test their efficacy as mass-transport limiting and tissue engineering membranes, with special focus on achieving reliable and long sensing life-time for biosensors when implanted in the body. The 3D structure of electrospun membranes provides the unique combination of extensively interconnected pores, large pore volumes and mechanical strength, which are anticipated to improving sensor sensitivity. Their structure also mimics the 3D architecture of natural extracellular matrix (ECM), which is exploited to engineer tissue responses to implants. A versatile vertical electrospinning setup was built in our workshop and used to electrospin single polymer - Selectophore™ polyurethane (PU) and two polymer (coaxial) – PU and gelatin (Ge) fibre membranes. Extensive studies involving optimization of electrospinning parameters (namely solvents, polymer solution concentration, applied electric potential, polymer solution feed flow rate, distance between spinneret and collector) were carried out to obtain electrospun membranes having tailorable fibre diameters, pore sizes and thickness. The morphology (scanning electron microscopy (SEM) and optical microscopy), fibre diameter (SEM), porosity (bubble point and gravimetry methods), hydrophilicity (contact angle), solute diffusion (biodialyzer) and uniaxial mechanical properties (tensile tester) were used to characterize certain shortlisted electrospun membranes. Static and dynamic collector configurations for electrospinning fibres directly on sensor surface were optimized of which the dynamic collections system helped achieve snugly fit membranes of uniform thickness on the entire surface of the sensor. The biocompatibility and the in vivo functional efficacy of electrospun membranes off and on glucose biosensors were evaluated in rat subcutaneous implantation model. Linear increase in thickness of electrospun membranes with increasing electrospinning time was observed. Further, the smaller the fibre diameter, smaller was the pore size and higher was the fibre density (predicted), the hydrophilicity and the mechanical strength. Very thin membranes showed zero-order (Fickian diffusion exponent ‘n’ ~ 1) permeability for glucose transport. Increasing membrane thickness lowered ‘n’ value through non-Fickian towards Fickian (‘n’ = 0.5) diffusion. Thin electrospun PU membranes (~10 μm thick) did not affect, while thicknesses between 20 and 140 μm all decreased sensitivity of glucose biosensor by about 20%. PU core - Ge shell coaxial fibre membranes caused decrease in ex vivo sensitivity by up to 40%. The membranes with sub-micron to micron sized pore sizes functioned as mass-transport limiting membranes; but were not permeable to host cells when implanted in the body. However, PU-Ge coaxial fibre membranes, having <2 μm pore sizes, were infiltrated with fibroblasts and deposition of collagen in their pores. Such tissue response prevented the formation of dense fibrous capsule around the implants, which helped improve the in vivo sensor sensitivity. To conclude, this study demonstrated that electrospun membrane having tailorable fibre diameters, porosity and thickness, while having mechanical strength similar to the natural soft tissues can be spun directly on sensor surfaces. The membranes can function as mass-transport limiting membranes, while causing minimal or no effect on sensor sensitivity. With the added bioactive Ge surfaces, evidence from this study indicates that reliable long-term in vivo sensor function can be achieved

Multifunctional mussel inspired coatings for orthopaedic applications

Dissertação de mestrado em Engenharia BiomédicaCurrently, there is still a significant rate of implant failures in clinical practice. Current solutions would consist of the development of robust, biocompatible, biodegradable coatings with enhanced adhesive and bioactive properties. So, in this work the development of multifunctional coatings inspired by adhesive properties of mussels and the robust nacre structure were proposed. Based on the configuration of the 3,4-dihydroxy-L-phenylalanine (DOPA) amino-acid of the mussel’s adhesive proteins, catechol groups were conjugated to chitosan (CHT) and hyaluronic acid (HA). Layer-by-layer (LbL) assembly was used to mimic the nacre structure, where the organic phase consisted of both polymers and the inorganic phase of bioactive glass nanoparticles (BGNPs). In parallel, polymeric LbL coatings were constructed for the sake of comparison. The modified polymers were characterized by ultraviolet-visible (UV-Vis) spectroscopy. The construction of various LbL configurations was monitored by quartz crystal microbalance and the adhesive properties were evaluated by lap shear adhesive tests. The bioactivity and the in-vitro cell behaviour were analysed for the coatings with and without BGNPs. In-vitro tests were conducted using the cell line L929. Hydroxyapatite deposition was evaluated by scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDS) and X-ray powder diffraction (XRD). Since the structure and topography play an important role in the functional performance of the films, two LbL assembly methods, dip- and spin-coating, were compared using three different substrates: glass, stainless steel, and titanium. The coatings were characterized by SEM, Fourier transform infrared spectroscopy (FT-IR), atomic force microscopy (AFM) and water contact angle (WCA). Given the enhanced adhesion and bioactivity of the developed films, they could be used as coatings of a variety of implants. In addition, spin-coating was found to be a particularly suitable method for the build-up, since films with smoother and more uniform surfaces were produced.Atualmente, ainda há uma percentagem significativa de falhas dos implantes na prática clínica. Soluções atuais envolveriam o desenvolvimento de revestimentos robustos, biocompatíveis, biodegradáveis, com propriedades adesivas e bioativas melhoradas. Assim, neste trabalho foi proposto o desenvolvimento de revestimentos multifuncionais inspirados nas propriedades adesivas dos mexilhões e na estrutura robusta do nácar. Baseado na configuração do aminoácido 3,4-dihidroxi-L-fenilalanina (DOPA) das proteínas adesivas dos mexilhões, foram conjugados grupos catecóis ao quitosano (CHT) e ao ácido hialurónico (HA). A montagem camada-a-camada (LbL) foi utilizada para mimetizar a estrutura do nácar, onde a fase orgânica consistiu em ambos os polímeros e a fase inorgânica nas nanopartículas de vidro bioativas (BGNPs). Paralelamente, foram construídos revestimentos LbL poliméricos para fins de comparação. Os polímeros modificados foram caracterizados por espectroscopia ultravioleta-visível (UV-Vis). A construção das várias configurações LbL foi monitorizada através da microbalança de cristal de quartzo e as suas propriedades adesivas avaliadas através de testes adesivos sob tensão de corte. A bioatividade e o comportamento celular in-vitro foram analisados para os revestimentos com e sem BGNPs. Os testes in-vitro foram realizados usando a linha celular L929. A deposição de hidroxiapatita foi avaliada por microscopia eletrónica de varrimento (SEM) acoplada com espectroscopia de energia dispersiva de raios-X (EDS) e por difração de raios-X (XRD). Uma vez que a estrutura e topografia apresentam um papel importante no desempenho funcional dos filmes, dois métodos de montagem LbL, revestimento por imersão e por rotação, foram comparados usando três substratos diferentes: vidro, aço inoxidável e titânio. Os revestimentos foram caracterizados por SEM, espectroscopia de infravermelho por transformada de Fourier (FT-IR), microscopia de força atómica (AFM) e ângulo de contacto da água (WCA). Dado à adesão e bioatividade melhoradas dos filmes desenvolvidos, estes poderiam ser utilizados como revestimentos para uma variedade de implantes. Além disso, verificou-se que o revestimento por rotação foi um método particularmente adequado para a construção, uma vez que foram produzidos filmes com superfícies mais lisas e uniformes

BIO-IONIC LIQUID FUNCTIONALIZED HYDROGELS TOWARDS SMART TISSUE REGENERATION

A blend of scaffolds, biologically active molecules, and cells are required to assemble functional constructs to repair and regenerate damaged tissue or organ via tissue engineering. The scaffold supports cell growth and proliferation and acts as a medium for diverse cellular activities. Even though hydrogel\u27s high-water content and flexible nature make it a pronounced applicant as a scaffold, they exhibit significant technical limitations such as the absence of cell-binding motifs, lack of oxygen, conductivity, adhesive properties, growth of cells in a 3-dimensional (3D) microenvironment. In this thesis, a novel material platform is evaluated and studied to address the concerns mentioned earlier. The biopolymer is made by conjugating a bio ionic liquid (BIL) onto a biocompatible polymer backbone. The introduction of choline functionality significantly enhances the polymer\u27s physical, mechanical, rheological, adhesive, and electrochemical properties. Initially, the adhesive properties and functionality of the synthesized biopolymers were analyzed. In addition, evaluating the biopolymer\u27s ability to be used in in-situ 3D printing in-vivo electrical stimulation studies was performed. Furthermore, to demonstrate the biopolymer\u27s performance as a conductive gel electrolyte, electrochemical functioning was considered. In conclusion, as an application, self-oxygenating tissue scaffolds were developed based on biocompatible electrochemical cell technology, combining the properties exhibited by the new class of biomaterials, an oxygen-generating setup that alleviates anoxia in a 3D microenvironment was confirmed, thus serving as an interface between bioelectronics and biomaterials

Additive manufacturing of sustainable biomaterials for biomedical applications

Biopolymers are promising environmentally benign materials applicable in multifarious applications. They are especially favorable in implantable biomedical devices thanks to their excellent unique properties, including bioactivity, renewability, bioresorbability, biocompatibility, biodegradability, and hydrophilicity. Additive manufacturing (AM) is a flexible and intricate manufacturing technology, which is widely used to fabricate biopolymer-based customized products and structures for advanced healthcare systems. Three-dimensional (3D) printing of these sustainable materials is applied in functional clinical settings including wound dressing, drug delivery systems, medical implants, and tissue engineering. The present review highlights recent advancements in different types of biopolymers, such as proteins and polysaccharides, which are employed to develop different biomedical products by using extrusion, vat polymerization, laser, and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional (4D) bioprinting techniques. This review also incorporates the influence of nanoparticles on the biological and mechanical performances of 3D-printed tissue scaffolds. This work also addresses current challenges as well as future developments of environmentally friendly polymeric materials manufactured through the AM techniques. Ideally, there is a need for more focused research on the adequate blending of these biodegradable biopolymers for achieving useful results in targeted biomedical areas. We envision that biopolymer-based 3D-printed composites have the potential to revolutionize the biomedical sector in the near future