NANOFIBER TECHNOLOGY: DESIGNING THE NEXT GENERATION OF TISSUE ENGINEERING SCAFFOLDS

Nanofiber technology designing the next generation of tissue engineering scaffolds l.jpg
1 / 36
0
0
738 days ago, 241 views
PowerPoint PPT Presentation
EXTRACELLULAR MATRIX. Flagging cell bond customized cell passing movement cytokine/development component action development separation. Segments collagens-elastin-hyaluronic corrosive proteoglycans-glycosaminoglycans-fibronectin. TISSUE ENGINEERING SCAFFOLDS - BACKGROUND. Premise-ECM microenvironment key to tissue recovery Cell not saw as independent unitRole of ECM-ECM mediat

Presentation Transcript

Slide 1

NANOFIBER TECHNOLOGY: DESIGNING THE NEXT GENERATION OF TISSUE ENGINEERING SCAFFOLDS C.P. Barnes 1 , S.A. Offer 1 , E.D. Boland 1 , D.G. Simpson 2 , G.L. Bowlin 1 Department of Biomedical Engineering, 2 Department of Anatomy and Neurobiology Virginia Commonwealth University, Richmond, VA MARK HWANG

Slide 2

Components - collagens - elastin - hyaluronic corrosive - proteoglycans - glycosaminoglycans - fibronectin EXTRACELLULAR MATRIX Signaling - cell adhesion -customized cell passing - migration -cytokine/development calculate action - growth -separation

Slide 3

TISSUE ENGINEERING SCAFFOLDS - BACKGROUND Premise - ECM microenvironment key to tissue recovery - Cell not saw as independent unit Role of ECM - ECM intervenes biochemical and mechanical flagging - Ideal ECM non-immunogenic promote development maintain 3-D structure only local tissues remain present treatment Research accentuations on date - Biocompatibility - Degradability

Slide 4

TISSUE ENGINEERING SCAFFOLDS - BACKGROUND Overall Goals - Design platform with most extreme control over: biocompatibility (compound) biodegradability (mechanical) - Utilize normal and manufactured polymers - Future bearings: tissue recovery drug conveyance EFFECTIVE SCAFFOLD DESIGN BEGINS WITH ACCURATE SCALING Current Focus - Nanofiber union

Slide 5

Scale distinction important - single cell contacts a huge number of strands - transmission of fine/unobtrusive signs NANOFIBERS - INTRODUCTION ECM filaments ~ 50-500 nm in measurement Cell ~ a few 10 um Fibers 1-2 requests of greatness < cell 3 methods to accomplish nanofiber scale - self get together - stage partition - electrospinning

Slide 6

Example: peptide-amphiphiles - hydrophobic tail - cysteine deposits  disulfide securities NANOFIBERS: SELF-ASSEMBLY Definition: unconstrained association into stable structure without covalent securities Biologically applicable procedures DNA, RNA, protein association - can accomplish little breadth Drawbacks: more perplexing in vitro - restricted to 1) a few polymers and - 2) hydrophobic/philic collaborations - little size; bigger = temperamental

Slide 7

NANOFIBERS: PHASE SEPARATION Definition: thermodynamic division of polymer arrangement into polymer-rich/poor layers - like setting a gel - control over macroporous engineering using porogens, microbeads, salts 98% porosity accomplished! - steady Drawbacks: - restricted to a few polymers - little creation scale

Slide 8

A-polymer arrangement in syringe B-metal needle C-voltage connected to need NANOFIBERS: ELECTROSPINNING Definition: electric field used to draw polymer stream out of arrangement D-electric field defeats arrangement surface pressure; polymer stream produced E-strands 1) gathered and 2) designed on plate

Slide 9

NANOFIBERS: ELECTROSPINNING - straightforward hardware - various polymers can be joined at 1) monomer level 2) fiber level 3) framework level - control over fiber distance across alter fixation/consistency - fiber length unlimited - control over platform engineering target plate geometry target plate rotational speed

Slide 10

NANOFIBERS: ELECTROSPINNING Drawbacks: - characteristic filaments 50-500 nm; spun filaments more like 500 nm - engineering exceptionally arbitrary LACK OF GOLD STANDARD Current methodologies consolidated systems - ordinarily electrospinning + stage partition - filaments woven over pores

Slide 11

NANOFIBERS: OVERVIEW

Slide 12

ELECTROSPINNING POLYMERS Synthetics - Polyglycolic corrosive (PGA) - Polylactic corrosive (PLA) - PGA-PLA - Polydioxanone (PDO) - Polycaprolactone - PGA-polycaprolactone - PLA-polycaprolactone - Polydioxanone-polycaprolactone Natural - Elastin - Gelatin collagen - Fibrillar collagen - Collagen mixes - Fibrinogen

Slide 13

POLYGLYCOLIC ACID (PGA) - biocompatible - reliable mechanical properties hydrophilic predictable bioabsorption (2-4 wks) - electrospinning yields measurements ~ 200 nm Parameters - surface region to volume proportion - turning introduction influences framework flexible modulus Drawbacks - fast hydrolitic debasement = pH change tissue must have buffering limit

Slide 14

POLYGLYCOLIC ACID (PGA) Random fiber accumulation (L), adjusted gathering (R)

Slide 15

POLYGLYCOLIC ACID (PGA) Fiber accumulation Orientation influences stretch/strain

Slide 16

POLYLACTIC ACID (PLA) – 200 nm - aliphatic polyester - L optical isomer utilized by-result of L isomer corruption = lactic corrosive - methyl amass diminishes hydrophilicity - unsurprising bioabsorption, slower than PGA (30 wks) - half-life perfect for medication conveyance Parameters (like PGA) - surface range to volume proportion - turning introduction influences framework versatile modulus Compare to PGA - low debasement rate = less pH change

Slide 17

POLYLACTIC ACID (PLA) – 200 nm Thickness controlled by electrospin dissolvable Chloroform dissolvable (L) ~ 10 um HFP (liquor) dissolvable (R) ~ 780 nm Both strands haphazardly gathered

Slide 18

PGA+PLA = PLGA - tried sythesis at 25-75, 50-50, 75-25 proportions - debasement rate relative to piece - hydrophilicity corresponding to organization Recent Study - conveyed PLGA platform heart tissue in mice - individual cardiomyocytes at seeding - full tissue (no platform) after 35 weeks - platform stacked with anti-microbials for wound recuperating

Slide 19

PGA+PLA = PLGA modulus corresponding to sythesis

Slide 20

POLYDIOXANONE (PDO) - crystalline (55%) - debasement rate between PGA/PLA close to 40-60 proportion - shape memory - modulus – 46 MPa; look at: collagen – 100 MPa elastin – 4 MPa Advantages - PDO ½ route between collagen/elastin, vascular ECM segments - cardiovascular tissue substitution (like PLGA) - thin filaments (180nm) Drawbacks - shape memory – less inclined to adjust with creating tissue

Slide 21

POLYCAPROLACTONE (PCL) - very versatile - moderate corruption rate (1-2 yrs) - > 1 um - comparative anxiety ability to PDO, higher flexibility Advantages - general better for cardiovascular tissue – no shape maintenance bc flexible Previous Applications Loaded with: - collagen  heart tissue substitution - calcium carbonate  bone tissue reinforcing - development elements  mesenchymal undifferentiated cell differentation

Slide 22

POLYCAPROLACTONE + PGA - PGA high anxiety resilience - PCL high versatility - improved blend PGA/PCL ~ 3/1 - bioabsorption no less than 3 mths (PCL-2 yrs, PGA 2-4 wks) Clinical Applications – none yet POLYCAPROLACTONE + PLA - PLA profoundly biocompatible (regular by items) - PCL high flexibility - more flexible than PGA/PCL - strain restrain increments 8x with only 5% PCL

Slide 23

POLYCAPROLACTONE + PLA - PCL versatile; however, diminishing PLA/PCL proportions diminishes strain limit - strain limit enhanced at 95:5 - still perfect in vivo – for the most part PLA = common by items

Slide 24

POLYCAPROLACTONE + PLA Clinical Applications - a few arranged - all vasculature tissue - high PLA rigidity react (tighten) to sudden weight increment - expanded flexibility with PCL passively oblige substantial liquid stream OVERALL – inactive extension, controlled choking = best manufactured ECM mix for heart application

Slide 25

POLYCAPROLACTONE + POLYDIOXANONE PCL PDO Recall… - PCL high flexibility - PDO approx = PLA/PGA - PDO shape memory – limits use in vascular tissue Findings - cross breed structure NOT = crossover properties - bring down pliable limit than PDO - low versatility than PDO - bigger breadth - NOT clinically valuable "[This] will be further explored by our research facility" at the end of the day not publishable, but rather 1 year of work and sufficient for an ace's theory

Slide 26

POLYCAPROLACTONE + POLYDIOXANONE PCL PDO Principle Drawbacks Large fiber width Low ductile/strain limit Possible Cause? PDO is the main crystalline structure polymer

Slide 27

ELASTIN - exceedingly versatile biosolid (benchmark for PDO) - hydrophobic - display in: vascular dividers skin Synthesis of Biosolid? - 81 kDa recombinant protein (ordinary ~ 64 kDa) - rehashed areas were included in restricting - 300 nm (not as little as PDO ~ 180 nm) - framed strips, not filaments – width fluctuates Findings: - not as flexible as local elastin - right now joined with PDO to increment elasticity - no clinical applications yet

Slide 28

COLLAGENS: FIBRIL FORMING Type I - 100 nm (not predictable) - practically indistinguishable to local collagen (TEM) - present is most tissues COLLAGENS: GELATIN - exceptionally dissolvable, biodegradable (extremely quick) - current accentuation on expanding life expectancy Type II - 100-120 nm (reliable) - found in ligament - pore size and fiber breadth effortlessly controlled by weakening

Slide 29

Type II simple to direct 1) fiber 2) pore measure COLLAGENS: FIBRIL FORMING Type I (conflicting strands)

Slide 30

COLLAGENS: FIBRIL FORMING Type III - preparatory reviews - seems steady ~ 250 nm None of the electrospun collagens have clinical application yet

Slide 31

Scaffolds examined to-date - remaking the media: COLLAGENS BLENDS In setting: vasculature - intima – collagen sort IV + elastin - media – thickest, elastin, collagen I, III, SMC - adventia – collagen I

Slide 32

- cross segment of tube divider - 5 day culture complete framework penetration RECONSTRUCTING THE MEDIA - SMC seeded into tube - normal fiber ~ 450 nm slightly bigger ECM filaments - consolidation of GAG carbohydrate ECM collagen crosslinker mediate flagging

Slide 33

COMBINING COLLAGEN WITH PDO Observations: - collagen I most elevated ductile limit - 70:30 collagen-PDO ideal proportion for all collagens

Slide 34

FIBRINOGEN - littlest distance across (both engineered and bio) 80, 310, 700 nm strands conceivable - high surface range to volume proportion increase surface association used in clump arrangement Stress limit similar to collagen (80-100 MPa)

Slide 35

HEMOGLOBIN - hemoglobin mats - clinical applications: drug conveyance hemostatic wraps - fiber sizes 2

SPONSORS