Materials Today Yoni

7/28/2019 Materials Today Yoni

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NOVEMBER 2012 | VOLUME 15 | NUMBER 11478 ISSN:1369 7021 Elsevier Ltd 2012

Nanomanufacturing

of biomaterials

In this review, we present a few of the many important objectives in the

area of biomedical engineering that could open new pathways for next-

generation biomaterials. We also provide examples of how materials forthese goals can be created in an economically viable means through recent

advances in high throughput production. These strategies highlight the

potential for nanomanufacturing in a variety of areas of importance for

human health and safety.

Yoni Engel1,, Jessica D. Schiffman2,,*, Julie M. Goddard3, and Vincent M. Rotello1,*1Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA2Department of Chemical Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA3Department of Food Science, University of Massachusetts, Amherst, Massachusetts 01003, USAThese authors contributed equally to this work*E-mail: [email protected];[email protected]

Controlling the interactions of surfaces with biological entities is

crucial for the development of smart and responsive biomaterials for

biomedical1,2, environmental, and food/water safety applications3.

Two factors, chemistry4 and nanotopography5 govern the interactions

that occur at the interfaces of anthropogenic materials and biology.

Controlling these interactions will provide materials with a range of

next-generation capabilities, including implantable medical devices

with tunable behavior6,7, tissue engineering scaffolds that can

encourage the growth of specific cell types 8,9, and biosensor surfaces

that can effectively resist protein and bacterial fouling2,10.

A wide range of materials including, polymers11-13

, carbohydrates14,15

,lipids16, peptides17, and proteins18,19 have been used to control the surface

properties of materials. A rapidly emerging direction in surface engineering is

the control of surface properties through nanostructuring20-22. Nanoparticles

(0D), wires and individual fibers (1D), thin films (2D), and fiber assemblies

(3D) can now be rationally synthesized23-26 and fine-tuned to elicit specific

interactions with the biological environment that are required for their

effective use27. Enhancing the surface of existing bulk materials (e.g., stainless

steel in the food industry, titanium for biomedical applications) with nano-

to micro-scale patterns, layers, and scaffolds of functional materials imparts

this control to commercially important substrates. This approach towards

nanofabricated surfaces couples desirable bulk materials properties, such

as mechanical stability and elasticity, with specific and tunable interactions

with the biological environment28,29.

Effective real-world implementation of biomaterials featuring

nanostructured surfaces requires translation of bench-scale success to

commercially scalable manufacturing. Traditional surface patterning and

topography modifying methods including optical, e-beam, or nanoimprint

lithography (NIL) are typically combined with various etching and

deposition techniques30-33. This post-processing increases the overall

processing cost and time while often introducing toxic materials, makingmany current nanofabrication techniques impractical for the commercial

production of nanostructured biomaterials.

In this mini-review, we present a few of the many important objectives

in the area of biomedical engineering that could open new pathways for

next-generation biomaterials.

Nanostructured anti-fouling and antimicrobialmaterialsThe undesired accumulation (i.e., fouling) of proteins and bacterial
mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]


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NOVEMBER 2012 | VOLUME 15 | NUMBER 11 4

Nanomanufacturing of biomaterials REVIEW

(a)

(c)

(b)

(d)

colonies on surfaces is a cause for concern in practically all biomedical

applications where surfaces are exposed to biological media. Protein

fouling can degrade bio-sensor performance34, induce immune response

and inflammation around implants35, and is often the first step in

microbial colonization and the growth of biofilms capable of causing

disease or spoilage3. Bacterial contamination poses serious health

hazards when formed on surgical equipment and biomedical devices36,

thus making the fabrication of biofouling resistant surfaces a priority in

biomedical engineering10. Cross-contamination of pathogenic organisms

in hospital and food processing environments also represents a major risk

to nosocomial infections and outbreaks of food borne illness, respectively.

Due to the array of grave responses that arise from protein and microbial

accumulation, strategies that target the various stages of both protein

and bacterial fouling are urgently needed.

Protein fouling is a three step process: 1) reversible protein adsorption,

2) denaturation, and 3) multilayer protein deposition. In previousstudies the Rotello group has demonstrated the utility of modified gold

nanoparticles (GNPs) as an active nanoscale agent for biomaterials20,

including the stabilization of adsorbed proteins37. This aspect has been

applied to the creation of surfaces highly resistant to protein fouling. In

this strategy GNPs were covalently attached in a robust and uniform

configuration to surfaces via dithiocarbamate (DTC) place exchange

reactions on their gold core38,39. Surfaces featuring positive, neutral, or

negative GNPs (Fig. 1a) were immobilized via dithiocarbamate formation

onto polyethylenimine (PEI) films (Fig. 1b). The GNP coated PEI surfaces

prevented the denaturation (Fig. 1c) and fouling of proteins, demonstrating

the ability of GNP paint to provide non-fouling surfaces (Fig. 1d).

Like protein fouling, bacterial adhesion proceeds in multiple steps40,41,

providing distinct opportunities to create antimicrobial surfaces.

One approach is to develop bio-inert surfaces that chemically resist

protein fouling, and hence, are also efficient in preventing the bacterial

attachment that follows (Figs. 2a,b). For example, Bandyopadhyay and

co-workers demonstrated that racemic D+L gulitol terminated surfaces

were more effective than homochiral surfaces in preventing protein

adsorption and biofilm formation42. The difference between chiral and

racemic surfaces was related to different water solvation at the interface,

which is considered to have an important role in determining the fouling

resistance of monolayer coated surfaces10. This work suggests integrating

different surface chemistries as a general anti-fouling approach to

attack different stages of the bacterial adhesion process.

Another approach to antimicrobial surfaces is to develop materialsthat can actively kill bacteria13. This approach was used by the Goddard

group to create antimicrobial surfaces with significance in food science

and biomedical applications43. Recently, Bastarrachea and Goddard

prepared stainless steel surfaces presenting antimicrobial N-halamine

functions44(Fig. 2c). High loading of N-halamines was achieved by

using a layer-by-layer assembly of PEI and Poly-acrylic acid (PAA) on

stainless steel surfaces, followed by the halogenation of amides, amines,

and imides in the assembled layers. N-halamines inactivate bacteria

through the direct oxidation of biomolecules within the microorganism.

Fig. 1 (a) Gold nanoparticles (NPs) used in this study featured a positive, neutral, or negative interacting tail. (b) Schematic depicts the anti-fouling behavior ofpristine PEI surfaces and GNP-coated-PEI surfaces. (c) CD spectra of BSA protein, thermally denatured BSA protein, and GNP-BSA protein complexes. (d) Ellipsometrymeasurements determined that differet thicknesses of proteins were adsorbed onto PEI, NP-coated-PEI, and PEG surfaces after incubation with solutions containing10%, 50%, and 100% of serum (FBS) for 6 h. Reproduced from20 with permission from Wiley.


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NOVEMBER 2012 | VOLUME 15 | NUMBER 11480

REVIEW Nanomanufacturing of biomaterials

(a)

(c)

(b)

(a) (b)

Fig. 2 Protein fouling is often the first stage in bacterial biofilm formation. Schematic depicts that (a) proteins accumulate on an untreated surface. (b) Surfaces whichare chemically modified with a passivation layer can prevent denaturation of proteins and are more resistant to biofilm formation. (c) A sta inless steel slide is coated withPEI and polyacrylic acid (PAA) using a layer-by-layer assembly technique. Exposure of the surface to bleach causes the N-chlorination of various nitrogen functionsin the multilayer assembly. High loading of strongly oxidizing chlorine in the bulk of the multilayer, and on its surface, results in efficient deactivation of bacteria. The

surfaces can be recharged with chlorine by re-exposure to a bleach solution.

Fig. 3 (a) SEM micrograph of inactivated Escherichia coli on electrospun polysulfone (PSf) mats containing a low weight percent (0.1 wt%) of immobilized single-walledcarbon nanotubes (SWNTs). Close-up micrograph revealed that SWNT ends were distributed along the longitudinal fiber axis. Fluorescence-based t oxicity assay resultsindicate that (b) loss of viability directly correlated to increased SWNT loading. The 100 wt% SWNT-coated commercial filters (solid white bar) exhibited only slightlyhigher toxicity (88 3%) than PSf mats loaded with 1.0 wt% SWNTs (76 5 %). Reproduced from45 with permission from the American Chemical Society.


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(a) (b)

(c)

(d)(e)(f)

The cell-materials interface: wound healingand tissue engineeringCell behavior and growth are highly sensitive to the chemical and

mechanical cues present in the nano- and micro-environment of tissues

and organs46. Nanomanufactured surfaces that are capable of controlling

cell behavior and proliferation can be used to induce desired cell growth

(e.g., bone or muscle) in a pre-defined geometry. Thus, nanoengineering

the cell-materials interface hold promise for tissue engineering and

regenerative medicine applications47,48

.Nanotopology is a key determinant of cell proliferation and spreading,

and is hence an integral aspect to tissue engineering 49. Cells adhere to

surfaces through receptors (integrins) on the cell surface that interact with

extracellular matrix (ECM) ligands (e.g., fibronectin). At focal adhesions

(FA) points where the cell are in contact with these ligands there is

a clustering of integrins and other cytoplasmic proteins to increase the

size and the strength of the adhesion site50. While fully developed FA

have sizes of between 1 10 m, the initially formed complex can be as

small as 100 nm51. Integrin ligand spacing52 on surfaces of scaffolds has

The N-halamine loaded stainless steel surfaces provided 99.999 %

inactivation of the bacteria Listeriamonocytogenes,an important food-

borne pathogen. A significant advantage of this approach is that these

surfaces can be recharged with commercial bleach (sodium hypochlorite,

NaClO) to regain their antimicrobial chlorinated structure.

Topology plays an important role in antimicrobial surfaces. Schiffman

and Elimelech electrospun polysulfone (PSf) scaffolds that featured a low

loading of immobilized narrow diameter single-walled carbon nanotubes

(SWNTs)45

,Fig. 3a. With these surfaces, antimicrobial activity occurredwithin a short contact time, 15 minutes or less. A relatively low loading

of SWNTs provided highly effective antimicrobial activity: 1 % (by

weight) SWNT loading provided nearly comparable toxicity to control

100 weight percent SWNT-coated filters, (Fig. 3b). The low loading of the

active nanomaterial agent and the ability to directly electrospin a mat

onto or apply it as a conformal coating to any surface where bacterial

colonization might occur, afford two insights into the emergence (Fig. 6b)

of electrospinning as a highly versatile fabrication technique, as described

in the following section.

Fig. 4 (a) Schematic depicts how cells arrange on pristine PEI and GNP-coated-PEI patterned surfaces. (b) Percentage cell viability is displayed for fibroblast cellspatterned on various surfaces. (c) Histogram of the cell alignment angle on NP3 modified aurfaces (nonpatterned or patterned) and on patterned PEI surfaces. Fluorescentmicrographs of cells on surfaces display (d) patterned NP3 surface, (e) patterned PEI surface, and (f) nonpatterned NP3 surface. Scale bar represents 20 m. Reproduced

from21 with permission from Wiley.


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(a) (b) (c)

(e) (d)

Fig. 5 (a) Schematic depicts surface bioactivation via the reactive-imprint lithography (RIL) process. Thermal imprinting is used to create nanostructures of activatedmaleimide. These structures are then modified with the arginine-glycine-aspartic acid (RGD) peptide using a thiolmaleimide click reaction. Fluorescence micrographsdisplay cells stained with acetomethoxy derivative of calcein (Calcein AM) that have been cultured on (b) an unpatterned maleimide surface, (c) an RGD immobilizedunpatterned surface, (d) a patterned surface without RGD, and (e) an RGD immobilized patterned surface. Scale bars represent 20 m. Insets are bright field images of

patterned surfaces, scale bars represent 2 m. Reproduced from61 with permission from Wiley.

a dramatic effect on the formation of FA: patterning surfaces with these

ligands dictates cell morphology, viability, and alignment8,53,54.Utilizing an

extension of colloidal lithography, Malmstrm and co-workers patterned

laterally organized 100 - 1000 nm protein patches over areas as large as

tens of centimeters55. By creating laterally organized FN patterns on such

large areas, this group was able to study the adhesion, morphology andspreading of whole cell populations, extending from the individual cell

or small population studies that were conducted prior to this work 18,56-58.

Their studies showed that cellular attachment occurs for ECM patch sizes

as small as 200 nm, and that the level of interaction between the cell and

the surface, correlates to the size of the FN patch.

Modified GNPs, discussed earlier in the context of anti-fouling surfaces

(Fig. 1a) are also capable of facilitating cell alignment. Subramani and

coworkers patterned PEI lines (300 nm wide, 100 nm high) on a silicon

surface using NIL, and further used DTC chemistry to decorate these lines

with modified GNPs21 (Fig. 4a). The resulting patterns were then used

to induce highly aligned and evenly spread NIH3T3 cell growth, with

cells displaying increased viability (Fig. 4b) on surfaces modified with

GNPs and an elongated morphology in the direction of the patterns

(Fig. 4c). Cell cultures on PEI surfaces that were modified with NP-3,

best demonstrated that superior control over cell growth is achieved on

GNP modified PEI lines (Fig. 4d), relative to non-modified, pristine PEI

patterns (Fig. 4e) or nonpatterned NP-3 modified surfaces (Fig. 4f). This

phenomena was related to the non-fouling properties of the GNP coated

surfaces. Surface ligands could communicate directly with cells without

the interference that can occur after protein adsorption onto surfaces.

The need for high throughput fabrication of biomaterials for applications

such as wound healing provides a challenge for nanomanufacturing of soft

materials. In one approach, simultaneous control over surface chemistry

and topography was obtained using reactive-imprint lithography (RIL)59.

RIL couples the high fidelity, resolution (


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(a)(b)

(c)

(h)

(e)

(i)

(j)

(f) (g)

(k)

(d)

absorbability, in a highly size-controlled fashion71. In electrospinning, a

viscous and charged precursor solution is forced out of a capillary that isconnected via electrodes to a grounded collector (Fig. 6a). As the voltage

is increased, the repulsive electrical forces pull the pendent drop into a

Taylor Cone (conical protrusion) and at a critical voltage, the electrical

forces overcome the surface tension forces resulting in the emergence

of a liquid jet72. Solvent instantly begins to evaporate as the jet is

stretched and whipped, generating a 2D non-woven scaffold composed

of solid nanofibers73 that can be used to generate clinically relevant 3D

biomaterials74-77(Fig. 6c-g).

Fibrous mats from over 100 different synthetic and natural polymers

Fig. 6 (a) The schematic displays an electrospinning apparatus that is composed of a spinneret, high voltage supply, and a collector. Typically, an advancement pump isused to regulate the flow rate of the polymeric solution. A SEM micrograph displays the fiber morphology present in a typical electrospun nanofiber mat. (b) Over the

past dozen years , the t otal number of electrospinning publications exhibit an upward t rend. Data acquired using the SciFinder Scholar database represent the uniquenumber of electrospinning search results as determined on June 22, 2012. Mats consisting of (c) random and (d) aligned fibers were electrospun onto films andassembled into conduits to foster the regeneration of vascularized CNS tissue. Two similar mats were (e) placed back-to-back (f) and rolled (g) into conduits having adiameter of 2.6 mm. Representative horizontal spinal cord sections displayed for (h) film, (i) random, and (j) aligned fiber conduits. Dotted lines indicate the walls of theconduits. (k) After four weeks, aligned fibers foster the robust rostrocaudal axonal regeneration, whereas the same response is absent in film and random fiber conduits.Reproduced from77with permission from Elsevier.

including poly(lactic-co-glycolic acid) (PLGA), poly(caprolactone)

(PCL), poly(ethylene oxide) (PEO), chitosan, hyaluronic acid, and silkprotein have been produced using electrospinning71,78-81.Post-fabrication

chemical surface modification using materials such as proteins, silver

nanoparticles, and drugs, can provide an even greater surface diversity75,82.

Modifying electrospun mats with peptides such as RGD sequences can

facilitate recognition by integrin cell surface receptors and mediate

cell cell and cell ECM adhesion83. Electrospun mats can also provide

3D materials for wound dressings, drug delivery systems, and tissue

engineering scaffolds. For instance, Hurtado et al. electrospun random

(Fig. 6c) and aligned (Fig. 6d) poly-L-lactic acid fibers and rolled them


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(a) (b)

(c)

into conduits (Fig. 6e-g) that provided a more robust regeneration of

vascularized central nervous system (CNS) tissue than film conduits (Fig.

6h-k). For these studies, conduits were grafted into a 3 mm thoracic

rat spinal cord gap created by complete transection77. In vivo studies

have demonstrated the clinical potential of electropun mats to achieve

a localized delivery of chemotherapuetic and nucleic acid agents84.

Electrospun ceramic mats have demonstrated potential for bone-graft

scaffolds due to their inherent biocompatibility and ability to induce

osteoconduction and osseointegration in orthopedic fractures and

defects85.

High throughput materials processingThe ability to impart desired bioactivity over large areas with high speed

and reproducibility will translate to numerous commercial applications.

Non-fouling surfaces3,86, biocompatible implanted devices87, antimicrobial

materials2,44,88, bioactive packaging89, biosensor component design20,90,91,

and enzymatically active materials92 represent only a fraction of

the bioactive surfaces that could be upscaled once high throughput

nanomanufacturing methods have been developed.

Roll-to-roll (R2R) and roll-to-plate (R2P) processes create continuous

coatings on flexible and hard substrates, respectively93. These techniques

can enable the nanomanufacturing of biomaterials, as their successhas already been demonstrated in the manufacturing of flexible solar

cells94 and printed electronics95. Many thin-film deposition techniques

are compatible with the R2R and R2P processes (i.e., flow coating, knife

coating, slot-die coating, meyer bar coating, and gravure coating)94,96,97,

and films as thin as 51 nm with a roughness of 3.7 nm have already been

demonstrated using the gravure coating method98.

Surface topography can also be modified using R2R and R2P processing.

By patterning the gravure cylinder with bioactive inks, fine structures

can be printed requiring only minimal amounts of active agents95,99. Ahn

and Guo have combined the high-speed R2R/R2P process with a modified

NIL patterning technique93,100 (Fig. 7a).Here, a liquid phase UV-curable

resist material was applied on the substrates (polyethylene or glass, Fig.

7b) and pressed against an ethylene tetrafluoroethylene (ETFE) patterned

mold. Exposure to UV-light cured the grating structures (300 nm lines,

Fig. 7c). The imprint mechanism and the resist materials selected for this

R2R-NIL process enabled short imprinting and curing times, making this

version of NIL compatible with high speed processing.

PerspectiveCommercial nanomanufacturing of biomaterials is a challenging prospect

offering a high payoff. As shown above, there have been a number of

techniques developed in the lab that have potential for high throughput

applications. One of the most promising strategies for industrial

application of these materials is the use of large area R2R and R2P

processes that have already found use in the manufacturing of printable

electronics. For this to happen, however, new methodologies will have

to be developed that can maintain the chemical integrity of delicate

biomaterials and the mechanical structure of high surface area-to-volume

materials such as electrospun nanofiber scaffolds. While the creation of

value-added materials for biomedicine does not require the same degree

of economy required for many other applications, economics will stillplay an important factor. Once effective and economical approaches

have been developed, however, there will be broad implications in the

biomedical community that will improve the quality of life around the

world.

AcknowledgmentsWe thank Katrina A. Rieger for her assistance in the preparation ofFig. 6.

This work was supported by the NSF Center for Hierarchical Manufacturing

at the University of Massachusetts (NSEC, CMMI-1025020).

Fig. 7 (a) Schematics of (top) the roll-to-roll nanoimprint lithography (R2R-NIL) and (bottom) the roll-to-plate (R2P-NIL) processes. (b) An epoxysilicone gratingspattern (4 in wide by 12 in long with a 700 nm period) was created on a flexible PET substrate using R2R-NIL. (c) SEM micrograph of the patterned grating structure.Reproduced from93 with permission from the American Chemical Society.


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References

1. Yiu, H. H. P., et al.,Adv Funct Mater(2010) 20 (10), 1599

2. Vasilev, K., et al., Expert Rev Med Devices (2009) 6 (5), 553

3. Merian, T., and Goddard, J. M.,J Agric Food Chem (2012) 60 (12), 2943

4. Alves, N. M., et al., Small (2010) 6 (20), 22085. Richert, L., et al.,Adv Mater(2008) 20 (8), 1488

6. Buser, D., et al.,J Dent Res (2004) 83 (7), 529

7. Thevenot, P., et al., Curr Top Med Chem (2008) 8 (4), 270

8. Stevens, M. M., and George, J. H., Science (2005) 310 (5751), 1135

9. Khor, E., and Lim, L. Y., Biomaterials (2003) 24 (13), 2339

10. Banerjee, I., et al.,Adv Mater(2011) 23 (6), 690

11. Goddard, J. M., and Hotchkiss, J. H., Prog Polym Sci(2007) 32 (7), 698

12. Yi, A. Y., et al.,Adv Polym Technol(2008) 27 (4), 188

13. Cheng, G., et al.,Angew Chem Int Ed(2008) 47 (46), 8831

14. Morra, M.,J Appl Biomater Biomech(2007) 5 (1), 1

15. Huang, Y., et al., Progress in Chemistry(2008) 20 (6), 942

16. Persson, F., et al., Nano Lett (2012) 12 (5), 2260

17. Costa, F., et al.,Acta Biomater(2011) 7 (4), 1431

18. Pesen, D., and Haviland, D. B.,ACS Appl Mater Interfaces (2009) 1 (3), 543

19. Elnathan, R., et al., Nano Lett (2012) 12 (10), 5245

20. Subramani, C., et al.,Adv Mater(2010) 22 (47), 5420

21. Subramani, C., et al., Small (2012) 8 (8), 1209

22. Jang, K.-J., and Nam, J.-M., Small (2008) 4 (11), 1930

23. Elnathan, R., et al., Nano Lett (2008) 8 (11), 3964

24. Pevzner, A., et al., Nano Lett (2012) 12 (1), 7

25. Yeh, Y. C., et al., Nanoscale (2012) 4 (6), 1871

26. Shchukin, D. G., and Sukhorukov, G. B.,Adv Mater(2004) 16 (8), 671

27. De, M., et al.,Adv Mater(2008) 20 (22), 4225

28. Stanford, C. M.,Adv Dent Res (1999) 13, 88

29. Stanford, C. M., Int J Mol Sci(2010) 11 (1), 354

30. Pevzner, A., et al., Nano Lett (2010) 10 (4), 1202

31. Nandwana, V., et al.,J Mater Chem (2011) 21 (42), 1685932. Kwiat, M., et al.,ACS Appl Mater Interfaces (2012)

33. Ofir, Y., et al.,Adv Mater(2010) 22 (32), 3608

34. Huang, C. J., et al.,Anal Chem (2012) 84 (7), 3440

35. Tirrell, M., et al., Surf Sci(2002) 500 (13), 61

36. Donlan, R. M., Problems of Biofilms Associated with Medical Devices andImplants. In Medical Biofilms, John Wiley & Sons, Ltd(2005), pp 29

37. Jordan, B. J., et al., Soft Matter(2006) 2 (7), 558

38. Park, M. H., et al.,Adv Mater(2008) 20 (21), 4185

39. Castelino, K., et al., Langmuir(2005) 21 (5), 1956

40. Stoodley, P., et al.,Annu Rev Microbiol (2002) 56 (1), 187

41. OToole, G., et al.,Annu Rev Microbiol (2000) 54, 49

42. Bandyopadhyay, D., et al., Langmuir(2011) 27 (10), 6124

43. Goddard, J. M., and Hotchkiss, J. H.,J Food Prot (2008) 71 (10), 2042

44. Bastarrachea, L. J., and Goddard, J. M.,J Appl Polym Sci(2013) 127 (1), 82145. Schiffman, J. D., and Elimelech, M.,ACS Appl Mater Interfaces (2011) 3 (2), 462

46. Kim, D. H., et al.,Adv Mater(2010) 22 (41), 4551

47. Curtis, A., and Riehle, M., Phys Med Biol (2001) 46 (4), R47

48. Kim, T. G., et al.,Adv Funct Mater(2012) 22 (12), 2446

49. Bettinger, C. J., et al.,Angew Chem Int Ed(2009) 48 (30), 5406

50. Lock, J. G., et al., Semin Cancer Biol (2008) 18 (1), 65

51. Geiger, B., et al., Nat Rev Mol Cell Biol (2009) 10 (1), 21

52. Arnold, M., et al., Chem Phys Chem (2004) 5 (3), 383

53. Berry, C. C., et al., Biomaterials (2004) 25 (26), 5781

54. Lauffenburger, D. A., and Horwitz, A. F., Cell (1996) 84 (3), 359

55. Malmstrom, J., et al., Nano Lett (2010) 10 (2), 68656. Arnold, M., et al., Soft Matter(2009) 5 (1), 72

57. Lehnert, D., et al.,J Cell Sci(2004) 117 (1), 41

58. Slater, J. H., and Frey, W., J Biomed Mater Res, Part A(2008) 87A (1), 176

59. Duvigneau, J., et al.,Adv Funct Mater(2010) 20 (3), 460

60. Guo, L. J.,Adv Mater(2007) 19 (4), 495

61. Subramani, C., et al.,Adv Mater(2011) 23 (28), 3165

62. Marklein, R. A., and Burdick, J. A.,Adv Mater(2010) 22 (2), 175

63. Chen, W., et al.,ACS Nano (2012) 6 (5), 4094

64. Tay, C. Y., et al., Small (2011) 7 (10), 1416

65. Holzwarth, J. M., and Ma, P. X.,J Mater Chem (2011) 21 (28), 10243

66. Yang, S. F., et al., Tissue Eng (2001) 7 (6), 679

67. Yang, Y., et al.,Adv Mater(2008) 20 (11), 2037

68. Lutolf, M. P., and Hubbell, J. A., Nat Biotechnol (2005) 23 (1), 47

69. Liu, X. H., and Ma, P. X., Biomaterials (2009) 30 (25), 4094

70. Whitesides, G. M., et al., Science (1991) 254 (5036), 1312

71. Schiffman, J. D., and Schauer, C. L., Polym Rev(2008) 48 (2), 317

72. Bellan, L. M., and Craighead, H. G.,J Manuf Sci E-T. ASME. (2009) 131 (3)

73. Shin, Y. M., et al., Polymer(2001) 42 (25), 09955

74. Ding, B., et al., Mater Today(2010) 13 (11), 16

75. Meinel, A. J., et al., Eur J Pharm Biopharm (2012) 81 (1), 1

76. Katti, D. S., et al.,J Biomed Mater Res, Part B (2004) 70B (2), 286

77. Hurtado, A., et al., Biomaterials (2011) 32 (26), 6068

78. Dzenis, Y., Science (2004) 304 (5679), 1917

79. Schiffman, J. D., et al., Polym Eng and Sci(2009) 49 (10), 1918

80. Brenner, E. K., et al., Carbohydr Polym (2012) 87 (1), 926

81. Schiffman, J. D., and Schauer, C. L., Biomacromolecules (2007) 8 (2), 594

82. Schiffman, J. D., et al., Langmuir(2011) 27 (21), 1315983. Mattanavee, W., et al.,ACS Appl Mater Interfaces (2009) 1 (5), 1076

84. Ranganath, S. H., and Wang, C. H., Biomaterials (2008) 29 (20), 2996

85. Dinarvand, P., et al.,ACS Appl Mater Interfaces (2011) 3 (11), 4518

86. Krishnan, S., et al.,J Mater Chem (2008) 18 (29), 3405

87. Biggs, M. J. P., et al., Nanomed Nanotech Biol Med(2010) 6 (5), 619

88. Lichter, J. A., et al., Macromolecules (2009) 42 (22), 8573

89. Tian, F., et al.,J Agric Food Chem (2012) 60 (8), 2046

90. Goddard, J. M., and Erickson, D.,Anal Bioanal Chem (2009) 394 (2), 469

91. Kwiat, M., et al.,J Am Chem Soc (2012) 134 (1), 280

92. Talbert, J. N., and Goddard, J. M., Coll and Surf B-Biointerfaces (2012) 93, 8

93. Ahn, S. H., and Guo, L. J.,ACS Nano (2009) 3 (8), 2304

94. Sondergaard, R., et al., Mater Today(2012) 15 (1-2), 36

95. Kang, H., et al.,Adv Mater(2012) 24 (22), 3065

96. Krebs, F. C., Sol Energy Mater Sol Cells (2009) 93 (4), 394

97. Tracton, A. A., Coatings Technology Handbook3rd ed.; CRC press: Bridgewater,New Jersey, USA, 2005

98. Kim, A., et al.,J Nanosci Nanotechnol (2010) 10 (5), 3326

99. Reddy, A. S. G., et al., Gravure Printed Electrochemical Biosensor. In EurosensorsXXV, Kaltsas, G., and Tsamis, C., (eds.) Elsevier Science Bv, Amsterdam, (2011),Vol. 25

100. Ahn, S. H., and Guo, L. J., Adv Mater(2008) 20 (11), 2044

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