Natural and synthetic polymers in medicine ppt [Autosaved].pptx

ShahRucksanaAkhterUr1 1,714 views 45 slides May 15, 2022
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A slide share about Natural & Synthetic Polymer in medicine. Figures, information's are collected from peer reviewed journals with latest information.


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N atural and Synthetic Polymers in Medicine Shah Rucksana Akhter URME Organic Chemical Technology Politechnika Krakowska Krakow, Poland May, 2022

AGENDA 1.What is Polymer and why in medicine. 2. History 3.Classification of Synthetic & natural polymers 4. Natural & Synthetic polymeric materials 5. Merits and demerits of Natural & Synthetic polymer 6. Types of Polymers & Application 7.Natural & Synthetic polymeric scaffold composites 8. Smart Polymeric Materials 9. Global Market of Polymers 10. Conclusions & References

What is Polymer? A polymer is any of a class of natural or synthetic substances composed of very large molecules, called macromolecules, which are multiples of simpler chemical units called monomers. Classification of Polymers based on source

Why Polymers in Medicine?

History A Brief Timeline of Polymers in Medicine 1860’s: Aseptic surgery introduced 1900’s: Metal bone plates used for breaks and fracture 1947’s: pMMA used in cornea replacement 1950-60’s: Artificial heart and Dialysis machines introduced polymers eventually make unite better . 1990-2000:More than half of biomaterial applications are made of or contain some polymers Beyond 2000:Drug delivery , Bioimaging & Biosensing , Synthesis & bioconjugation , Implant coating , Tissue Engineering etc.

Natural polymers Naturally derived polymers are suitable for medical applications because of Biocompatibility, Biodegradability, Non-toxicity, Ability to adsorb bioactive molecules . Natural polymers have been widely used in biomedical applications such as pharmaceuticals, tissue regeneration scaffolds, drug delivery agents, and imaging agents . Natural polymers, also called biopolymers , are naturally occurring materials, formed during the life cycles of green plants, animals, bacteria, and fungi .

Classification of Natural Polymers Natural Polymers Animals Plants Microbes Polysaccharides : Cellulose, Starch etc. Polysaccharides: Cellulose, Starch etc . Proteins: Gelatine , Albumin etc. Polysaccharides: Chitin, Chitosan Etc. Polyesters: Polyh ydroxyalkanoates ( PHAs )  etc. Nucleic acids: DNA, RNA etc .

Example of Natural Polymer Production/Extraction Figure : A schematic representation of the chemical and biological (enzymatic) methods for chitin extraction P. Rameshthangam et al.,2018

Natural Polymeric Materials CELLULOSE Properties Major sources of cellulose are plant fibers, bacteria. L inear chains of glucose units linked by β-1,4-glycosidic bonds. Advantages Stable matrix, mechanical strength for tissue engineering. Hydrophilicity Biocompatibility Bioactivity Disadvantages Non-degradable or Slowly degradable. Application Wound dressing Drug delivery Tissue Engineering Blood purification Bacterial Cellulose

Cellulose-based monomers Figure: Schematic diagram of integrated routes to potential cellulose-based monomers for sustainable polymer production H .Shaghaleh et al.,2018

Natural Polymeric Materials ALGINATE Properties Made up of carboxylic groups Material properties varies from building block of the alginate. Advantages Mimiking ; gel forming material, Bioabsorbable ; Hydrophilicity; Biocompatibility; Bioactivity. Disadvantages Difficult to sterilize, Low cell adhesion. Application Form of hydrogel for biomedicine Drug release Wound healing etc. Alginate

Natural Polymeric Materials COLLAGEN Properties Made up of amino acids group: Glycine, Proline, Hydroxyproline Advantages Favorable to Cell adhesion, proliferation, differentiation. Low immunogenicity Bioabsorbable ; Hydrophilicity; Excellent Biocompatibility; Bioactivity. Disadvantages Difficult to disinfection Poor Stability Application Scaffold as tissue filler Support matrix for matrix –rich tissues Collagen

Natural Polymeric Materials Hyaluronic Acid Properties β -D glucoronic acid and β-1,3- N- acetyl -D- glucosamide . Advantages Encapsulation capability Cell activity Non-immunogenic Nonantigenic Biocompatibility; Osteo-compatibility Disadvantages Mechanical properties need fine tuning Low biodegradability Application L ubricant in the joints and other tissues Skin treatment Hydration, Hydrogel Hyaluronic Acid

Advantages & Disadvantages Natural Polymers Major advantages to natural polymers Lower/no toxicity, Better bioactivity, Enhanced cell response when associated with cells, Excellent biocompatibility, Extreme hydrophilicity and effective biological function. Significant drawbacks of natural polymers • Complicated isolation techniques from inconsistent sources. • Poor processability and solubility blocking the utilization of industrial fabrication processes. • Possibility of contamination by pyrogens and pathogens. Poor or limited material properties like elasticity, ductility, strength, and shelf life. Immunogenic & chance to allergic reaction. Low mechanical properties and easily degradable. • High cost.

Synthetic Polymers Synthetic polymers  are man-made polymers produced by chemical reactions. Synthetic polymers have been used for numerous biomedical and pharmacologic purposes. These include  prosthetic implants, suture material and drug carriers etc. Synthetic polymers : P olyvinyl chloride (PVC), polypropylene (PP), P olyethylene (PE), P olystyrene (PS), nylon, Polyethylene terephthalate (PET), P olyimide (PA), P olycarbonate (PC), A crylonitrile butadiene (ABS), polyetheretherketone (PEEK) P olyurethane (PU).

Classification of Synthetic Polymers Synthetic Polymers Poly-ethers Poly-amides Poly-esters Poly- anhydried Polyethylene Glycol Polypropylene Glycol Polylactic acid Polyglycolic acid Polycaprolactone Poly-amino acid Poly amino carbonate Poly adapic acid Poly sebacic acid

Synthetic Polymeric Materials Poly-lactic acid(PLA) Properties Linear highly crystaline polyester Advantages Hydrophilicity; Biocompatibility; High melting point Disadvantages Highly sensitive to hydrolysis Application O rthopedic fixation tools, ligament and tendon repair, vascular stents Poly Lactic Acid

Synthetic Polymeric Materials Poly-glycolic acid(PGA) Properties Highly crystaline A synthetic homopolymer of glycolic ( hydroacetic ) acid Advantages Excellent Mechanical strength; Biocompatibility; Cytocompatibility; Thermal stability Disadvantages Hydrophobicity Brittleness Application O rthopedic fixation tools, ligament and tendon repair, vascular stents Poly-glycolic Acid

Synthetic Polymeric Materials Poly-hydroxybutyrate acid(PHB) Properties Naturally occuring b-hydroxy acid ; It is a homopolymer having a stereoregular structure with high crystalinity . Advantages Non-toxic Biostable Advantages over PLA and PGA Biocompatibility; Disadvantages Thermal instability Application Biocontrol agents Biodegradable implants Memory enhancher Anti-cancer agent Poly Hydroxy-Butyrate

Synthetic Polymeric Materials Polyvinyl alcohol Properties Semicrystalline polyhydroxypolymer Prepared via hydrolysis of poly vinyl acetate Advantages Biocompatibility; Non-Toxic Good lubrication; Tensile strength similar to human articular cartilage; Non-carcinogenic Disadvantages Lack of cell adhesive properties Less ingrowth of bone cells Application A ntifouling coating or for hydrogel formation nucleus pulposus or vitreous body replacement. Polyvinyl alcohol

Synthetic Polymers Major advantages to synthetic polymers G ood strength, F lexibility, Less immunogenic & less allergic reaction compared to natural polymer, C hemical inertness, A bility to be fabricated into a wide range of shapes and sizes. Customized design Significant drawbacks of Synthetic polymers P oor biocompatibility R elease of acidic degradation products, P oor processability and L oss of mechanical properties very early during degradation

Types of Polymers & Application Figure : Natural and synthetic polymers are arranged based on bio vs non-bio and biodegradable vs nonbiodegradable characteristics . MSB Reddy et al., 2021 C. Kalirajan et al., 2021 Figure : Schematic illustrating the applications of polymeric biomaterials in different biomedical field.

Polymeric Scaffold The term “scaffold” refers to an artificial temporary platform applied to support, repair, or to enhance the performance of a structure. Biocompatibility, biodegradability, mechanical characteristics, pore size, porosity, osteoinductivity , osteoconductivity , osteogenesis, and osteointegration are the key design considerations for the scaffold.

Polymers for Scaffolding Scaffolds can be used ranging from regenerative engineering to managed drug delivery and immunomodulation. Consideration of selecting polymers: Support for new tissue growth. Prevention of cellular activity. Guided tissue response. Improvement of cell connection and consequent cellular activation. Inhibition of cellular attachment and/or activation. Prevention of a biological response.

Natural and Synthetic Polymer composites Scaffold materials Fabrication method Scaffold application Collagen Freeze-drying Vascular tissue engineering Pectin Freeze drying Neo -cartilage tissue regeneration , surgical manipulation Chitosan Lyophilization Clinical purposes Alginate- coated PLLA Lyophilization Designing engineered tissues Methylcellulose Combination of film casting and lyophilization methods Drug delivery vehicles and skin tissue engineering Gelatin Electrospinning and 3D printing Nasal cartilages and subchondral bone reconstruction PVC Electro- spinning Bone tissue engineering

Bio- degradability of Polymer Scaffolds MSB Reddy et al., 2021

Bio-compatibility of Polymer Scaffolds The capacity of a biomaterial to execute its intended purpose concerning medical therapy without affecting the therapy from suffering any adverse local or systemic effects. Figure : The essential variables that define the scaffold’s biocompatibility . MSB Reddy et al., 2021

The essential variables involved in scaffold design for TE Scaffolds used in Tissue Engineering follows some key factors. After implemented in a body, the scaffold should aim to Be a liable structure for adhesion, proliferation, and cell differentiation as a substratum, Create the required biomechanical environment for coordinated regeneration of tissues, Permit the dissemination of nutrients and oxygen, and Allow cells to be encapsulated and released with growth factors MSB Reddy et al., 2021 Figure: The essential variables involved in scaffold design for TE

Degradation Mechanism of biodegradable polymer scaffolds Polymers name Degradation method Application Alginate Enzymatic Bone and cartilage tissue substitutes Gelatin Hydrolysis , dissolving , transformation, and enzyme- catalyzed decomposition Cartilage cells Starch /PVA Hydrolytic Bone tissue engineering Collagen /PLLA Enzymatic Tissue engineering PCL Hydrolytic (surface erosion ) Drug delivery and tissue engineering PGA Hydrolytic Tissue- engineered vascular grafts PLA/ thermoplastic polyurethane Enzymatic Tissue engineering MSB Reddy et al., 2021

Different types of polymeric scaffolds for tissue engineering A.3D Porous Matrix : Thermodynamic demixing of a homogeneous polymer/solvent solution. F.3D Bioprinting : Computer-aided design model ; Construct a 3D architecture with a precise control of characteristics; Highly reproducible scaffolds ; Customized shape and Size. B. Nanofiber Mesh C. Porous Microsphere: porosity, pore morphology, mechanical properties, bioactivity, and degradation rates of the scaffolds are controlled by varying process parameters. D. Hydrogel E. Micelle

Different Forms of Natural and Synthetic Smart Polymeric Biomaterials Polymeric Films Easy to prepare & low cost . Studied for wound dressing materials Flim containing biomedicine have antimicrobial properties . Figure: The simple schematic shows the self-healing mechanism of cationic chitosan matrix assisted by anionic filler (Poly(acrylic acid) grafted bacterial cellulose). C. Kalirajan et al., 2021

Polymeric Sponges Material Category Materials Properties Application Polymeric Sponges Agarose and chitosan 3D Scaffold Liver tissue model Gelatin Scaffold Cartilage extracellular matrix Fibroin / chitin /silver nanoparticles Scaffold Antibacterial activity Collagen and ZnO nanoparticles Scaffold Wound dressing material Gelatin and PVA Scaffold Cytocompatible biomaterial for skin regeneration Natural and synthetic polymers-based 3D scaffolds/sponges have wide applications in skin and bone tissue engineering. C. Kalirajan et al., 2021

Hydrogels Figure : The schematic illustration showing the preparation of fiber reinforced GelMA ( gelatin methacyrylate ) hydrogel for of the regeneration of the damaged corneal stroma. Hydrogels have been prepared from natural polymers known for their application in corneal defects. High aqueous environment, biocompatibility, and high transparent nature. C. Kalirajan et al.,2021

Injectable Hydrogels Figure: Schematic representation of the treatment of myocardial infarction using the coadministration of the adhesive conductive hydrogel patch and injectable hydrogel. In tissue engineering strategies, injectable hydrogels and biomaterial cardiac patches have been used to treat myocardial infarctions. Researchers prepared hydrogels from the two natural polymers gelatin and hyaluronic acid. C. Kalirajan et al., 2021

3D Printed Hydrogels Figure: Schematic representation shows the 3D Printing of Water-Based Light-Cured Polyurethane with Hyaluronic Acid scaffolds for Cartilage Tissue Engineering Applications . Articular cartilage diseases affecting millions of people worldwide, one study probed 3D printed cytocompatible hydrogel for tissue engineering applications . C. Kalirajan et al., 2021

Bio- Inks Bio-ink is used in 3D printing for the preparation of different shaped and sized biomaterials or implants. Figure: Schematic presentation of 3D bioprinting with composite bioink Z.Maan et al.,2022

Cell sheet detachment from a thermo-responsive surface. For this specific application, thermo-responsive polymers are designed to be hydrophobic at 37°C the ideal condition for cell seeding and adhesion, and hydrophilic at room temperature. ( a) Cells adhere to a hydrophobic surface through membrane proteins and ECM( Extracellular Matrix), forming cell junctions . (b) Both membrane and ECM proteins are disrupted through enzymatic digestion, causing cellular detachment . (c) Cells cultured on a thermo-responsive surface can be harvested as a contiguous cell sheet , maintaining cell to- cell junctions by lowering the temperature . C Kalirajan et al., 2021 Figure: Cell sheet detachment from a thermo-responsive surface

Physical or chemical stimuli in biopolymers Smart responses to: Shape recovery, Gelation, Macromolecule disruption, Swelling, Fluorescence. C. Kalirajan et al., 2021

Some commercially available biopolymer systems for various types of tissue repair Source: Copyright 2014. Reproduced with permission from Biomedical Engineering Society Product Application Product description TachoSil * Cardiac Wound sealant Contains human fibrogen & thrombin to form fibrin sealant NeuroFlex * Nerve repair and regrowth Type 1 collagen mesh NeuroMatrix * Nerve repair and regrowth Type 1 collagen mesh NeuroMend * Nerve repair and regrowth Type 1 collagen mesh Dynamatrix * Soft Tissur reconstraction Acellular graft containing collagen - 1, 2,3 INFUSE* Bone Repair Absorbable collagen sponge in a metal

Global market of Polymers Source: https://www.alliedmarketresearch.com/medical-polymers-market

Global market of Polymers Source: https://www.alliedmarketresearch.com/medical-polymers-market

Conclusions and Future Prospects An ideal biomaterial for regenerative medicine should be nontoxic, biocompatible and promoting cellular interactions to tissue development, with adequate mechanical and physical properties Implementing biopolymeric systems in therapeutics applications as capability to scale up with controlled and targeted properties, could be a significant step for the future The Polymeric material plays the role as matrix or drug release modifers , viscosity modifers , binding agents, flm coating substances, gelling agents, and bioadhesives etc. A scaffold made from a composite containing both natural and synthetic biopolymers can permit tissue substitutes to be produced that satisfy all clinical requirements , Medical polymers are extensively used in the medical devices and packaging, and in the pharmaceutical sector increasing demand for medical polymers, which will boost the industry The development of patient-specific, smart polymeric biomaterials represents the future of polymer-based biomaterials.

References Altomare , L., Bonetti, L., Campiglio, C. E., De Nardo , L., Draghi, L., Tana, F., & Farè , S. (2018). Biopolymer-based strategies in the design of smart medical devices and artificial organs.  The International Journal of Artificial Organs ,  41 (6), 337-359. Biswas, M. C., Jony , B., Nandy , P. K., Chowdhury, R. A., Halder, S., Kumar, D., ... & Imam, M. A. (2021). Recent Advancement of Biopolymers and Their Potential Biomedical Applications.  Journal of Polymers and the Environment , 1-24. Chen, S., Zhang, Q., Nakamoto, T., Kawazoe, N., & Chen, G. (2016). Gelatin scaffolds with controlled pore structure and mechanical property for cartilage tissue engineering.  Tissue Engineering Part C: Methods ,  22 (3), 189-198. He, X.; Fan, X.; Feng, W.; Chen, Y.; Guo, T.; Wang, F.; Liu, J.; Tang, K. Incorporation of microfibrillated cellulose into collagenhydroxyapatite scaffold for bone tissue engineering. Int. J. Biol. Macromol . 2018, 115, 385–392 Shaghaleh , H., Xu, X., & Wang, S. (2018). Current progress in production of biopolymeric materials based on cellulose, cellulose nanofibers, and cellulose derivatives.  RSC advances ,  8 (2), 825-842. Kalirajan , C., Dukle , A., Nathanael, A. J., Oh, T. H., & Manivasagam , G. (2021). A Critical Review on Polymeric Biomaterials for Biomedical Applications.  Polymers ,  13 (17), 3015. Maan , Z., Masri , N. Z., & Willerth , S. M. (2022). Smart Bioinks for the Printing of Human Tissue Models.  Biomolecules ,  12 (1), 141. Nyambat , B.; Chen, C.-H.; Wong, P.-C.; Chiang, C.-W.; Satapathy , M.K.; Chuang, E.-Y. Genipin -crosslinked adipose stem cell derived extracellular matrix-nano graphene oxide composite sponge for skin tissue engineering. J. Mater. Chem. B 2018, 6, 979–990. Rameshthangam , P., Solairaj , D., Arunachalam , G., & Ramasamy , P. (2018). Chitin and Chitinases: biomedical and environmental applications of chitin and its derivatives.  Journal of Enzymes ,  1 (1), 20-43. Reddy, M. S. B., Ponnamma , D., Choudhary, R., & Sadasivuni , K. K. (2021). A comparative review of natural and synthetic biopolymer composite scaffolds.  Polymers ,  13 (7), 1105. Shie , M. Y., Chang, W. C., Wei, L. J., Huang, Y. H., Chen, C. H., Shih, C. T., ... & Shen, Y. F. (2017). 3D printing of cytocompatible water-based light-cured polyurethane with hyaluronic acid for cartilage tissue engineering applications.  Materials ,  10 (2), 136. Tripathi , A., & Melo, J. S. (2015). Preparation of a sponge-like biocomposite agarose–chitosan scaffold with primary hepatocytes for establishing an in vitro 3D liver tissue model.  RSC Advances ,  5 (39), 30701-30710.

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Questions What is polymer? Mention some merits and demerits of the Natural and Synthetic Polymer in Medical Science. What is Polymeric Scaffold? Describe some natural polymers with application. Mention 3 smart polymeric biomaterials with specificity .