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Smart Hydrogels. Andrea Cosimi 29, May 2019 Biomaterials and Tissue Engineering. Hydrogels First studies related to hydrogels appeared in 1894 Number of publications showed exponential growth over the last ten years. Main applications :. Smart Hydrogels – Introduction.
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Smart Hydrogels Andrea Cosimi 29, May 2019 Biomaterials and Tissue Engineering Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Hydrogels • First studies related to hydrogelsappeared in 1894 • Number of publicationsshowedexponentialgrowth over the last tenyears • Mainapplications: Smart Hydrogels –Introduction • Middle of the 20° century, theyweretermedas water-swollencrosslinkedpolymeric networks Tissue scaffold Super absorbent Cell immobilization Woundhealing Contactlenses Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels • The word «smart» wasintroduced in 1948 by Kuhn and co-workers • Delivery concept denominatedas «smart» becauseit can detectprevailingstimuli and respondthroughstructural, morphological or functionalchanges • Theiruniqueproperties can be • associated with environmentalfactors • The dynamic nature of supramolecularchemistry makes itapplicable to the development of smart hydrogels • The finalmorphologyexpected for the hydrogelisassociated with a series of variables, whichprimarilyincludes the synthesis or treatment procedures of the originalpolymer, monomercomposition and their ratio Smart Hydrogels – Introduction • First publicationaboutpoly (acrylic acid), PAA, moleculesthatcouldundergostructuraladjustmentsaccording with the media pH Journal of Controlled Release 194 (2014) 1-19 Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels • A set of criteriahasbeenused to classifythese systems, includingorigin (natural or synthetic), degradability and cross-linking mechanism. • By manipulating the factorsinvolved in these links, we control the structuralproperties of the final system • Expectedresponses can be manifold and include degradation, drug release, swelling, changes in shape or surface, conformationalmodifications or micellization • Responsiveness Smart Hydrogels – Classification Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Thermo-responsive • As medium temperature mayfluctuate in physiological and pathologicalconditions, thermo-responsive hydrogels are one of the moststudied classes of stimuli systems in tissue engineering and drug delivery research • Thermo-responsive hydrogels can be dividedintotwo groups: lowercriticalsolution temperature (LCST) and uppercriticalsolution temperature (UCST) • From 2005 to 2010, only 44 publications per yearwereaddressed to UCST against 330 included LCST • Severalpolymers can be included in both LCST and UCST classes, e.g. PEO, which shows a loop-shapedmiscibility gap with UCST > LCST. PAAsPAMsSulfonate Phasetransitionphenomenon. (a) LCST and (b) UCST phasetransitionbehaviors of thermo-responsive polymers in solution Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Thermo-responsive • For LCST hydrogels, atlower T°, water molecules are arrangedaround the polymer. The increase of environmental T° reduces the energy associated to the water-polymer interaction. Thus, the polymerdehydrates, transformingitselfinto a more hydrophobicstructure and causingphaseseparation Stimuli-responsive behaviour of PNIPAAm. Source: MaterialMatters 2010, 5.3, 56 Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Thermo-responsive PNIPAAm for use as a smart culture surface Source: Material Matters 2010, 5.3, 56 ThermosensitiveinjectablePNIPAAm-hyaluronic acid copolymerhydrogel for adipose tissue engineering Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Light-responsive • Smart Hydrogels – Light-, electric- and magnetic- responsive • Electric, magnetic fields, and light exposure are the mainexternalphysicalstimuliused to tunedrug release kinetics from smart hydrogels. Once thisstimuli can be controlled, theyhave the advantage of modulatingdrug release spatially and temporally. • Photo-sensitive polymers can change their physicochemical properties or degrade in response to light irradiation of appropriate wavelength and intensity. • Two types of UV light response: photopolymerization and photocleavage systems • Photopolymerization: Chemical structure of light-responsive moieties employed in the synthesis of photo-responsive polymers. K. Peng , I. Tomatsu and A. Kros , Chem. Commun., 2010, 46 , 4094 -4096 Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Light-responsive • Photocleavage: • Disadvantages in using UV light • low penetration • potentiallycarcinogenic • A valid alternative is the use of UCNPs, which are able to convertphoton energy absorbed from NIR light into UV light Photodegradablepolymericmaterialscontaining (a) a photolabilejunction, (b) photo-labile pendant groups, (c) photodegradablebackbone and (d) photo-labile cross-linkers Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Electric-responsive • Smart Hydrogels – Electric- and Magnetic-responsive • Electro-responsive systems are materials that respond to an applied electric field by changing their size or shape. They are termed as electro-conductive hydrogels (ECHs), developed from polyelectrolytes or from ICPs. • The development of magnetic nanomaterials has been the source for the discovery of spectacular new phenomena, with potential applications in numerous fields • HFMFs are less invasive than electric fields or light exposure • Magnetichydrogelsdeveloped by inclusion of MIONs in the polymermatrices. MIONs/polymer ratio determines the saturationmagnetization and consequently the drug release performance Chemical structures of some conductivepolymers. From top leftclockwise: polyacetylene; polyphenylenevinylene ; polypyrrole (X = NH) and polythiophene (X = S); and polypyrrole (X = NH) and polyphenylenesulfide (X = S). Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – pH-responsive • The human body exhibits subustantial pH changes in different body parts when functioning normally. Additionally, some diseases can also cause pH changes in the human body • Similar to macromolecules, a polymer network contains ionizable groups that can donate or accept protons in response to pH. In aqueous solutions they are polyelectrolytes • Two classes of pH responsive hydrogels pH values in severalhealthytissues and cellcompartments Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – pH-responsive • pH-responsive behavior can also be found among natural polymers such as alginate, albumin, chitosan, pectin and gelatin • Chitosan and alginate are representative natural polyacid and polybasepolysaccharides, that suffer physical cross-linking through hydrophobic or charge interactions Alginate Chitosan Explanation of pH-dependent water permeationthrough (a) a porous membrane and (b) a dense membrane Crystal structure of Chitosan Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Salt- or ionicstrenght-responsive • Important feature of hydrogels, considered that some biological processes such as nerve excitation, muscle contraction and cell locomotion involve ionic strength modification • Generally, the mechanism of the ionic strength-responsive polymers is that the added salt will reduce the electrostatic interactions between copolymers or between polymers and other molecules • Some weak PAAs and MAAs show an increased degree of ionization upon addition of lithium methoxide salt • Hydrogels composed PNIPAM exhibit LCST; its behavior showed also a sharp volume phase transition depending on the NaCl concentration • A PNIPAM hydrogel with specificsensitivitywassynthetized by introducing di-benzo-18-crown-6 comonomersinto the network Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Bio-responsive • Changes might occur in response to increased concentration of specific biomolecule availability • Antibodies, T cells and enzymes are important biomolecules which can be used as important signals for disease diagnosis • Many research groups have focused in the development of smart self-regulated biomaterial systems, useful for drug delivery as well as for diagnosis, cell cultures, biosensors or matrices for tissue engineering and regenerative medicine • Three types of responsiveness • Glucose • Enzyme • Antigen • Glucose-repsonsive are widelyused in diabetes treatment with different strategies for insulin self-regulation • Glucoseoxidase (GOX) • Lecitin (concanvalin A) • Phenylboronic acid Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Glucose-responsive • Changes might occur in response to increased concentration of specific biomolecule availability • Antibodies, T cells and enzymes are important biomolecules which can be used as important signals for disease diagnosis • Many research groups have focused in the development of smart self-regulated biomaterial systems, useful for drug delivery as well as for diagnosis, cell cultures, biosensors or matrices for tissue engineering and regenerative medicine • Three types of responsiveness • Glucose • Enzyme • Antigen • Glucose-repsonsive are widelyused in diabet treatment with different strategies for insulin self-regulation • Glucoseoxidase (GOX) • Lecitin (concanvalin A) • Phenylboronic acid Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Glucose-responsive • Changes might occur in response to increased concentration of specific biomolecule availability • Antibodies, T cells and enzymes are important biomolecules which can be used as important signals for disease diagnosis • Many research groups have focused in the development of smart self-regulated biomaterial systems, useful for drug delivery as well as for diagnosis, cell cultures, biosensors or matrices for tissue engineering and regenerative medicine • Three types of responsiveness • Glucose • Enzyme • Antigen • Glucose-repsonsive are widelyused in diabet treatment with different strategies for insulin self-regulation • Glucoseoxidase (GOX) • Lecitin (concanvalin A) • Phenylboronic acid Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Glucose-responsive • Changes might occur in response to increased concentration of specific biomolecule availability • Antibodies, T cells and enzymes are important biomolecules which can be used as important signals for disease diagnosis • Many research groups have focused in the development of smart self-regulated biomaterial systems, useful for drug delivery as well as for diagnosis, cell cultures, biosensors or matrices for tissue engineering and regenerative medicine • Three types of responsiveness • Glucose • Enzyme • Antigen • Glucose-repsonsive are widelyused in diabet treatment with different strategies for insulin self-regulation • Glucoseoxidase (GOX) • Lecitin (concanvalin A) • Phenylboronic acid (PBA) Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Glucose-responsive • Changes might occur in response to increased concentration of specific biomolecule availability • Antibodies, T cells and enzymes are important biomolecules which can be used as important signals for disease diagnosis • Many research groups have focused in the development of smart self-regulated biomaterial systems, useful for drug delivery as well as for diagnosis, cell cultures, biosensors or matrices for tissue engineering and regenerative medicine • Three types of responsiveness • Glucose • Enzyme • Antigen • Glucose-repsonsive are widelyused in diabet treatment with different strategies for insulin self-regulation • Novelglucose-responsive system based on covalentdynamic bonds Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Enzyme-responsive • In cellular environment, most stimuli-responsive mechanisms are under control of enzymes • Since enzymes are highly selective in their reactivity, responsiveness is specific • First application related to tissue engineering for cartilage repair and chondrocyte culture • Enzyme-repsonsive are alsowidelyexploited to release drugsspecifically in the colon • Biodegradablepolymers include naturallyderivedpolymerssuchaspectin, amylose, gelangum, chitosan, alginate and dextran • Artificial non-biodegradablepolymers include PEG, PEO, pHEMA, PNIPA • Antigen-responsive hydrogels are able to undergo volume or structuralchanges in the presence of antibodies Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Smart Hydrogels – Functional delivery systems • The application of these bioactuating systems requires a sophisticated molecular design, which increases their potential application • Some disease are known for significant changes on the homeostasis state • Pathological aspects that can be explored toward this objective • Inflammatory processes • Cancer therapy • Diabetes mellitus • Which applications of smart polymers will likely succeed in clinic and why? • Tissue Engineering • Harder to simulate bodily environment for tests • Also, difficult to assess performance of grafts/ scaffolds/other devices in vivo • May be developed for longer-term applications, so in turn it will take longer to test the materials • Depends on whether you want to implant polymer scaffold with cells or wait for scaffold to degrade before implantation • Drug delivery • Short-term operation, so it may take less time to complete testing • Simple methods available to study release in vitro and able to test drug concentration for in vivo tests • Smart diagnosticapplications • Testing material, ifnot in body the regulations are mucheasier to meet/test Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering
Andrea Cosimi | 29.05.2019 | Biomaterials and Tissue Engineering