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Natural Fibers and Innovative Biomaterials i for Medical lapplications Dr. Michael Wöltje 33rd International Cotton Conference Bremen, 17.03.2016 Classification of textile fibers Textile fibers Natural fibers Chemical fibers Plant (Cotton, linen etc.) Regenerated fibers Synthetic fibers Animal (Wool, silk etc.) Chitin (Chitosan) Mineral (Glass, aramid, asbestos etc.) Regenerated cellulose (viscose) Regenerated protein (silk, soybean, keratin) Polyester Polyamide Polyacrylonitrile Polyurethane Polypropylene M. Wöltje Bremen 2016 Page 2 1

Classification of medical textile products Healthcare and hygiene Non-implantable materials Extracorporeal devices Implantable materials M. Wöltje Bremen 2016 Page 3 Healthcare and hygiene Surgical gowns Cotton, polyester, viscose rayon, polypropylene Caps and masks Viscose rayon, polyester Surgical covers, drape cloths Polyester, polyethylene Bedding, blankets, sheets, pillow covers Source: Bundesverband Medizintechnologie Cotton, polyester Uniforms, protective clothing Cotton, polyester, polypropylene Surgical hosiery Cotton, polyamide, polyester, elastomeric yarns M. Wöltje Bremen 2016 Page 4 2

Extracorporeal devices Devices used to support the function of vital organs Artificial kidneys (Dialyzers) remove waste products form patients blood Synthetic hair-sized hollow fibers (Cellulose or polyester) Artificial livers Separate and dispose of patient plasma and supply fresh plasma Cellulose hollow fibers Mechanical lungs Source: Fibron AG Remove carbon dioxide from patients blood and supply fresh oxygen Polypropylene hollow fibers or hollow silicone membrane M. Wöltje Bremen 2016 Page 5 Non-implantable materials Absorbent pads, wound contact layer Cotton, viscose, silk, polyamide, polyethylene Simple bandages, elastic bandages Cotton, viscose, polyamide, elastomeric fiber and yarn Plaster Viscose, polyester, polypropylene, perforated films Gauze Cotton, viscose, alginate, chitosan Wadding Cotton, viscose, wood-pulp M. Wöltje Bremen 2016 Page 6 3

Implantable materials: Biological requirements Suitable artificial surface for adherence and growth of cells. Porosity to enable cell ingrowth and encapsulation. Non-toxicity of fiber polymers or fabrication techniques. Biocompatibility for interaction with the host in a controlled and predictable way. Hemocompatibility without damaging blood cells or cause formation of destructive blood clots. Biodegradability or bio-stability depending on the application. Mechanical requirements must be met according particular application. Quelle: biocer M. Wöltje Bremen 2016 Page 7 Implantable materials (1) Sutures for surgery and wound closure Biodegradable: polyglycolide, catgut, polylactide Source: B Braun Non-biodegradable: silk, polyester, polypropylene, polyamide, PTFE, polyethylene Source: cp-medical M. Wöltje Bremen 2016 Page 8 4

Implantable materials (2) Cardiovascular implants Vascular grafts: Polyester, PTFE Stent grafts: Polyester, PTFE Artificial heard valves: Polyester mechanical Source: St. Jude Medical biological Source: B. Braun Source: Jotec Source: Labcor M. Wöltje Bremen 2016 Page 9 Implantable materials (3) Soft tissue implants 1. Artificial tendon and ligament: PTFE, PVDF, polyester, polyamide, polyethylene, silk Source: Biomedical Structures 2. Hernia meshes: Polypropylene, polyester, PTFE Source: Kebomed M. Wöltje Bremen 2016 Page 10 5

Natural fibers from biopolymers (chitosan 1) Chitosan isolation process Source: Arthropods, fungi and algae widely available biopolymer (polysaccharide) Bioresorbable, non-allergic, bacteria- and mould-repressive Process: 1. washing, drying, grinding, g, sieving 2. demineralization and deproteinization => chitin powder 1. ceacetylation 2. washing, drying, grinding, sieving => chitosan M. Wöltje Bremen 2016 Page 11 Natural fibers from biopolymers (chitosan 2) Chitosan wet spinning Chitosan powder (deacetylation 90-95%, medical grade) Wet spinning using acetic acid, winding, washing, drying and quilling M. Wöltje Bremen 2016 Page 12 6

Chitosan scaffolds for cartilage regeneration (1) Cartilage defects (knee) Aging g Mechanical stress Risk factors (sports, overweight, leg deformities, ) Low regeneration capacity of cartilage tissue Lack of blood vessels and blood flow source: https://physione.wordpress.com/2013/12/ 15/knee-pain/ surce: http://www.preserveyourjoints.co m/autologous-cartilage-implantationsave-your-joints.html source: www.mayoclinic.orgmedical-professionals clinical-updatesorthopedic-surgeryinnovationsmanaging-articular-cartilage-defects-knee M. Wöltje Bremen 2016 Page 13 Chitosan scaffolds for cartilage regeneration (2) Tissue Engineering Goal: Generation of target tissues Scaffolds are an essential component to deliver cells to the defect Biocompatibility and -degradability Adhesion growth and differentiation of stem cells Mechanical stability cells in hydrogel fibres substrate Implant M. Wöltje Bremen 2016 Page 14 7

Chitosan scaffolds for cartilage regeneration (3) Flock process Single component system: Chitosan: Substrate Glue Short fibers Deformation stable Biocompatible Flock Electrostatic t ti field fibers Glue Flock structure Substrate 30-80 kv Flock fibers Glue Substrate M. Wöltje Bremen 2016 Page 15 Natural fibers from biopolymers (silk 1) Silk fibroin Source: Cocoons of larvae of the silkmoth Bombyx mori Silk thread consists of two main proteins: sericin (glue like protein) and fibroin the structural protein Fibroin elementary unit: H 6 L 6 P25, MW 2.3 MDa 350 kda 26 kda 30 kda (Inoue et al., Eur. J. Biochem. 2004, 271, 356-366) Bioresorbable, non-allergic and biocompatible after complete removal of sericin (degumming) M. Wöltje Bremen 2016 Page 16 8

Natural fibers from biopolymers (silk 2) Regeneration of silk protein fibroin Boiling of cocons Incubation in 9.3 M LiBr Adopted from Rockwood et al. 2011 Nature Protocols Harsh processing destroys native protein folding structure of silk protein requires refolding reduces quality 230kDa silk protein fragments M. Wöltje Bremen 2016 Page 17 Natural fibers from biopolymers (silk 3) Processing of native silk fibroin Isolation of native silk fibroin solution from silk glands of silkworms. Pure native silk fibroin has a molecular weight of 2.3 MDa. Wet spinning and functionalization (Spintec Engineering GmbH). Silk Silk + HA Silk gland dissection Isolation of native fibroin Biomimetic spinning and functionalization Biospun fibers M. Wöltje Bremen 2016 Page 18 9

Textile scaffolds for bone regeneration (1) Bone defects Difficult therapeutic problem in reconstructive surgery Reconstructive surgery on the skeletal system needs bone substitutes Autologous grafts are the best method for healing bone defects Restrictions Limited availability of autologous bone Reasonableness of required additional surgery (comorbidity at donor site) Source: https://www.mech.kuleuven.be/en/bme/research/images/ image_aurelie M. Wöltje Bremen 2016 Page 19 Textile scaffolds for bone regeneration (2) Artifical implants Implants made of metal alloys have good strength and high long-term stability Disadvantages: Lack of regeneration conveying capacity, Stress shielding" Need to renewal especially in younger patients due to growth. M. Wöltje Bremen 2016 Page 20 10

Generation of textile scaffolds by NSN Technology (1) Net-Shape Nonwoven Technology (NSN) Additive manufacturing technology Short fiber layers Selective adhesive application and Layer-by-layer 3D construction Porosity of each layer can be adjusted by fiber length and fiber diameter Any desirable geometry possible Pore-size gradients by adjusting layer sequence M. Wöltje Bremen 2016 Page 21 NSN scaffolds for bone tissue regeneration (2) Manufacturing patient specific implants Scanning patients bone defect and modeling the scaffold geometry Slicing the CAD-file Generating machine tool paths via CAM Modelling NSN scaffold using GeoDict software M. Wöltje Bremen 2016 Page 22 11

Additional functionalization of NSN scaffolds Collagen coating using electrospinning Single component scaffold system is used (Chitosan) Process-integrated electrospinning is established Continuous functionalization with Nanofibers was achieved Degradation properties and immune responses remain unchanged Continuous nanofiber functionalization Smooth nanofibers forming networks Collagen coated chitosan NSN scaffolds M. Wöltje Bremen 2016 Page 23 Conclusion & Outlook Textile implants can be generated via multiple textile technologies, e.g. Flock technology NSN-technology The presented technologies allow generating textile implants with Interconnected pores Adjustable mechanical stability Excellent cell reaction Suitable degradation behavior Further research is focused on Process automation Adaption to other natural fibers and biomaterials Conducting multiple tests on cell behavior and cell response M. Wöltje Bremen 2016 Page 24 12

Many thanks for your kind attention M. Wöltje Bremen 2016 Page 25 13