Nanoscale Phase Separation and Water Uptake in Polymeric Biomaterials

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1 Nanoscale Phase Separation and Water Uptake in Polymeric Biomaterials Matthew R. Libera Stevens Institute of Technology Hoboken, New Jersey

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4 Triton Technology Application Note 024 Uniform water distribution Heterogenous water distribution

5 Bioresorbable Polymers for Tissue Engineering

6 Hydrolytic Polymer Degradation Ex: O H 2 O O R 1 C X R 2 R 1 C OH + HX R 2 Where X= O, N, S O O O R 1 C O R 2 R 1 C NH R 2 R 1 C S R 2 Ester Amide Thioester A.J Coury in Biomaterials Science 2nd ed. B. Ratner et al. Elsevier 2004) Degradation of poly(lactic acid)

7 Tyrosine-Derived Polycarbonates and Copolymers Poly(DTE carbonate): R = ethyl (2 carbons) O CH 2 CH 2 C NH CH CH 2 C O R O O O C O n DTE DTE co 5%PEG 1000 DTE co 30%PEG 1000 Yu and Kohn, Biomaterials 20 (1999) 253. hydrophilic PDTE hydrophobic

8 Polymeric Biomaterial Erosion and Nanoscale Morphology D water vs hydrolysis rate Surface Erosion Bulk Erosion Time A. Gopferich and J. Tessmar Adv. Drug Del. Rev. p911 (2002) Implications: - degradation rate - mechanical integrity - cell infiltration and tissue regeneration

9 How to Image Water at Nano Length Scales? Transmission Electron Microscopy (TEM) Traditional methods for generating image contrast: Heavy-element staining Defocus/phase contrast Emerging methods for generating image contrast: Electron holography Spatially resolved spectroscopy Constituents in a material can be differentiated from each other based on characteristic spectral fingerprints

10 Transmission Electron Microscopy (TEM) and Electron Energy-Loss Spectroscopy (EELS) STEM or TEM Core-shell excitation t < 100 nm Zero-loss Imaging Valence-shell excitation Spectroscopy

11 Low-Loss Spectral Database PVP PEG PDTD carb PDTE carb PCl water QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture Energy Loss (ev)

12 Quantitative Compositional Analysis at Each Pixel Reference spectra pixel size = 75 nm 1 μm Counts MLS fitting Energy loss (ev) Energy loss (ev) Energy loss (ev) Sun et. al., Ultramicroscopy 50 (1993) 127.

13 Water Mapping in PVP-PS Hydrophobic-Hydrophilic Blend 1.0 PS Frozen hydrated 1 micron Dry (sublimated ice) PVP pixel size = 100 nm dose = 400 e/nm 2 Water 0

14 Dose-Limited Spatial Resolution Optics-limited resolution Fraction Undamaged k 2 d 2 = C 2 f D A. Rose (1948) I = I o exp (-D/D crit ) 1/e Dose (e/nm 2 ) Dose (C/cm 2 ) Dose Rose D crit Damage Threshold Rose Minimum 1 Detectable Feature (nm) Feature Size (nm) Spot size - signal trade off pm [112] Si Nellist et al., Science, V305, p1741, 2004

15 Scatter Diagrams to Extract Statistically Significant Data Water map A. Sousa, A. Aitouchen, M. Libera, Ultramicroscopy, 2006 wt. fraction water wt. fraction hydrophilic

16 Resorption of PDTE-co 8% PEG1000. Compression-molded coupons in water at 20 o C t=0 2 days 5 mo 12 mo Nominal PEG ~ 17 wt% water ~ 14 wt% (wgt gain) experimental calculated Energy loss (ev) Thakur and Michniak Time (days) water = (13.2 ± 3.6) wt% PEG ~ 17 wt%

17 Water Mapping in PDTE-co-8% PEG days in water HAADF STEM water map 200 nm PEG map 200 nm 15 nm pixel size

18 Water-PEG Scatter Little Erosion after 5 Months 2 days 5 months wt. fraction water wt. fraction PEG wt. fraction water wt. fraction PEG PDTE-co-8%PEG1000.

19 HAADF STEM Water Mapping in PDTE-co-8% PEG Months in water Water map PEG map 200 nm nm 15 nm pixel size

20 Erosion via Nanoscale Water-Rich Channels wt% PEG wt% water a) c) b) Distance (nm) d) Distance (nm) e f 2 1 Top view 200 nm 1: 30 nm-width channels 2: 45 nm-width channels 3: 60 nm-width channels 1 2 3

21 Extensive Degradation and Bulk Erosion of PDTE-co-8% PEG1000 HAADF STEM 200 nm 12 Months in 20 o C, 2 37 o C Sousa, Jaap, Kohn, Libera Macromolecules, in press

22 Nanoscale Percolated Water-Rich Channels Provide Fast Diffusion Paths during Bulk Erosion Bulk Erosion Time Flux of water-soluble degradation products

23 Nanoscale Polymer Morphology and Control of Bulk Erosion Homopolymer Random copolymer The size and spatial distribution of hydrophylic 2nd phases offers a means to control resorption Block copolymer Homopolymer blend

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