contributed original article integrating nanotechnology into … nanotechnology... · 2017. 4....

28 SVC BULLETIN I SPRING 2017

inteGratinG nanoteChnoloGy into mediCine: Past, Present, and future

conTriBuTeD oriGinal arTicle

An acute shortage of organs is one of the most urgent challenges facing the healthcare sector, due to disease, trauma, congenital defects, and most importantly, age-related maladies. Synthetic materials used in to-day’s medical device applications are typically composed of millimeter- or mi-cron-sized particles, grains, and/or fibers. Although human cells are on the micron scale, their individual components, e.g., proteins, are composed of nanometer fea-tures. As a result of this size structure, the study of nanotechnology (or the use of ma-

Fig. 1—Schematic of how nanostructured surface features can be created on implant surfaces to control surface energy to influence the adsorption and bioactivity of proteins known to change cellular behavior.

terials with at least one dimension in the na-noscale) in medicine has increased tremen-dously over the past several decades[1,2]. Only nanomaterials can mimic the nano-structured features found in natural tissues. Nanotechnology has enabled the creation of materials that can exactly match the di-mensions of natural materials to improve tissue growth. Moreover, nanomaterials can possess unique surface energy (without changing chemistry) to control the initial protein adsorption that cells depend on to function (Fig. 1).

Thomas J. Webster, Northeastern University, Boston

SVC.Bulletin.Spring2017.indd 28 3/20/17 5:10 PM

SVC BULLETIN I SPRING 2017 29

nanotech-nology has enabled the creation of materials that can exactly match the dimensions of natural materials to improve tissue growth.

nanotech-nology has enabled the creation of materials that can exactly match the dimensions of natural materials to improve tissue growth.

TECHNOLOGYSVC.Bulletin.Spring2017.indd 29 3/20/17 5:10 PM

Nanotechnology Applications in Medicine

Two main areas where nanotechnology is being incorporated into medicine include: (a) the use of nanoparticles, and (b) the inclusion of nanostructured surface features. While research on the use of nanoparticles in medicine has significantly en-hanced our knowledge of immune system recognition (or rather the lack thereof), targeted drug delivery, biofilm pene-tration, and so much more, it is clear that using nanoparticles adds an extra risk of toxicity, unintended biodistribution, and biopersistence, requiring additional caution[3,4].

In contrast, it can be argued that regulatory concerns should be much lower for the design, fabrication, and use of nano-structured implant surfaces that do not change in chemistry but do change in nanoscale topography[1,2]. Numerous ex-amples of significantly improved biological functions (such as bone growth, vascular growth, and bacteriostatic surfaces) exist with regard to traditional materials created with a na-noscale surface to achievequick regulatory approval[3–11].For example, titanium alloys with nanoscale surface features created by anodization, severe plastic deformation, electron beam evaporation, and other deposition processes all repre-sent a form of nanotexturing that can improve bone forma-tion without introducing new chemistries into the body that are not currently approved by the Food and Drug Administra-tion (Fig. 2)[5,6].

Other studies have demonstrated that ceramics such as hydroxyapatite—when coated on titanium or other implant

surfaces using electrophoretic deposition—can create nano-scale surface features, which not only increase bone cell func-tions, but also decrease bacteria attachment and growth, all without using antibiotics (Fig. 3)[10].

Silicon nitride has also been shown in vivo to completely eliminate bacteria growth and improve bone growth when possessing nanoscale surface features in a rat calvaria infec-tion model for three months (Fig. 4)[8].

In fact, some researchers actually proposed a mathemati-cal equation that can predict the size of a nanoscale surface feature one should create on an implant to change surface en-ergy that can control initial protein adsorption and bioactivity events to increase tissue growth and/or decrease infection[9].

Future of Nanotechnology in MedicineClearly, while the aforementioned studies provide significant promise for the immediate regulatory approval of today’s medical devices that improve biological performance, all of these approaches are in reaction to a patient’s health prob-lem, and this cannot be the future of medicine. World popula-tion growth is increasing at an alarming rate, yet our medical treatments are still too reactionary and not tailored to each individual’s needs. Far too often, today’s medical approach leads to a prescription that only treats disease symptoms and not the source of the problem. For example, patients receive medical treatment, for the most part, only when medical prac-titioners react to their pain and suffering from broken bones, infections, etc. Other elements of modern society do not work

inTeGraTinG nanoTechnoloGY inTo MeDicineconTriBuTeD

oriGinal arTicle


Fig. 2—Bone pins anodized to possess nanoscale tubes (i.e., nanotubes) have been shown to increase bone growth and decrease bacteria functions without using pharmaceutical agents or antibiotics.

LOW MAGNIFICATION (10K) LOW MAGNIFICATION (10K)

HIGH MAGNIFICATION (100K) HIGH MAGNIFICATION (100K)

NANOTUBULAR PIN

ANODIZATION

RAISED PEAK

GROOVED VALLEY



Fig. 3—Increased bone growth and decreased bacteria functions have been measured on Ti treated with a nanoscale hydroxyapatite coating as depicted on the right side micrograph, compared to a micron scale hydroxyapatite coating on the middle micrograph and plain titanium on the left micrograph. The nanoscale hydroxyapatite coating (right) was produced by electrophoretic deposition, while the micron scale hydroxyapatite coating (middle) was created via plasma spray deposition, a technique used to improve orthopedic implant osseointegration[10]. Scale bars = 1 micron.

Fig. 4—Increased bone growth and decreased bacteria functions have been measured on a nanotextured silicon nitride surface (left) com-pared to smooth silicon nitride surface (right). The rat calvaria infec-tion model was used to simulate bacterial growth for three months[8].


conTriBuTeD oriGinal arTicle inTeGraTinG nanoTechnoloGY inTo MeDicine

ture directions of medicine as well. Specifically, researchers are creating hip implants that can respond to an individual’s immune system and detect in real time what type of cells are growing next to an implant (Fig. 5)[11]. Such hip implant sen-sors can communicate via wireless radio frequency technol-ogy to a clinician to relay if too many bacteria are present or not enough bone growth has occurred. Moreover, these same sensors can be externally activated to release biomolecules to reverse adverse biological events in real time before a prob-lem occurs. While much more work can be done, these sen-sors represent predictive, rather than reactionary, medicine.

Lastly, many research groups are creating synthetic im-mune cells that can be used to kill unwanted bacteria in the body (Fig. 6). In this manner, modern society is moving closer to personalized medicine using nanotechnology.

SummaryIn summary, the world of nanotechnology coatings and pro-cesses is very bright, not only due to new materials that can significantly improve the ones we are implanting today (with-out changing their chemistry), but also by developing new sensors and immune cells that allow for more predictive per-sonalized medicine. It is exciting to see what the future holds for the integration of nanomaterials into medicine.

References1. H. Liu and T.J. Webster, Nanomedicine for Implants: A Review of Stud-

ies and Necessary Experimental Tools, Biomaterials,28(2),pp.354–369, 2007.

2. L. Zhang and T.J. Webster, Nanotechnology and Nanomaterials: Promises for Improved Tissue Regeneration, NanoToday, 4(1),pp.66– 80, 2009.

Fig.6—An image of drug-resistant E. coli being attacked by synthetic immune cells. Scale bar = 1 micron.


this way. Think, for example, do we only fix a bridge when it collapses, killing all of those on it? Our medicine needs to become more predictive and proactive, anticipating patient needs and fixing them before they become problematic or life threatening.

Moreover, it is now well established that while most of us have similar components to our immune system (the same cells, same molecular pathways, etc.), parts of our immune system are quite different from one another. We all have dif-ferent life experiences and have exposed our bodies to differ-ent chemicals. A “one-size-fits-all” medical approach—where one patient may be cured by the same treatment that could kill another patient—is highly problematic. Modern medicine needs to become more personalized and less generalized.

Nanomedicine is offering potential solutions in these fu-

Fig. 5—A hip implant sensor that measures, via resistance, the type of cells that attach to the implant[11]. The sensor is composed of multi-walled carbon nanotubes grown out of anod-ized nanotubular titanium. The hip implant sensor can also communicate biological events surrounding the implant to a handheld device or computer in real time. Through the use of a biodegradable conductive implant coating, the sensor can release biomolecules to fight infec-tion, reverse inflammation, and grow bone through external electrical activation.

Computer

Analyzer instrument

e.g., Multi-walled carbon nanotubes grown out of nanotubular titanium electrode measuring bone growth/loss, infec-tion, and inflammation

Radio frequency signal

e.g., Nanostructure polypyrrole film immobilized antibiotics coating



the Use of Pharmaceuticals, International Journal of Nanomedicine, 9, pp.1775–1781,2014.

11. S. Sirinrath, R. Pareta, and T.J. Webster, Electrically Controlled Drug Release from Nanostructured Polypyrrole Coated on Titanium, Nano-technology, 22(8),pp.1201–1222,2011.

About the Author: Thomas J. WebsterThomas J. Webster is the director of the Nanomedicine Laboratories and has com-pleted extensive studies on the use of nanophase materials in medicine. He was appointed department chair of Chemical Engineering at Northeastern University in

2012. He is the founding editor-in-chief of the International Journal of Nanomedicine. Webster has received numerous honors including: Fellow of both the American Institute for Medical and Biological Engineering and the Biomedical En-gineering Society, recipient of the International Materials Re-search Chinese Academy of Science Lee-Hsun Lecture Award, and member of the International College of Fellows. He was recently elected president of the U.S. Society for Biomaterials. Webster has appeared on BBC, NBC, ABC, Fox News, the Weather Channel and many other news outlets talking about science. For more information, email [email protected]. SvC

3. E. Taylor and T.J. Webster, Reducing Infections through Nanotechnol- ogy and Nanoparticles, International Journal of Nanomedicine, 6, pp.1011–1022,2011.

4. J.T. Seil and T.J. Webster, Antimicrobial Applications of Nanotechnol-ogy: Methods and Literature, International Journal of Nanomedicine, 7,pp.2767–2781,2012.

5. S. Puckett, E. Taylor, T. Raimondo, and T.J. Webster, The Relationship Between the Nanostructure of Titanium Surfaces and Bacterial At-tachment, Biomaterials, 31(4),pp.706–713,2010.

6. B. Ercan, E. Taylor, E. Alpaslan, and T.J. Webster, Diameter of Titanium Nanotubes Influences Anti-bacterial Efficacy, Nanotechnology, 22(29), pp.957–971,2011.

7. L. Liu, B. Ercan, L. Sun, and T.J. Webster, Understanding the Role of Polymer Surface Nanoscale Topography on Inhibiting Bacteria Adhesion and Growth, ACS Biomaterials-Science & Engineering, 2(1), pp.122–130,2016.

8. T.J. Webster, A.A. Patel, and M.N. Rahaman, Anti-infective and Osteo-integration Properties of Silicon Nitride, Poly (Ether Ether Ketone), and Titanium Implants, Acta Biomaterialia, 8(12), pp. 4447–4454,2012.

9. D. Khang, S.Y. Kim, P. Liu-Synder, G.T.R. Palmore, S.M. Durbin, and T.J. Webster, Enhanced Fibronectin Adsorption on Carbon Nanotubes/Poly (Carbonate) Urethane: Independent Role of Surface Nano Rough-ness and Associated Surface Energy, Biomaterials, 28(32),pp.4745–4768, 2007.

10. D. Mathew, G. Bhardwaj, Q. Wang, and T.J. Webster, Decreased Staph-ylococcus Aureus and Increased Osteoblast Density on Nanostruc-tured Electrophoretic-deposited Hydroxyapatite on Titanium Without

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contributed original article integrating nanotechnology into … nanotechnology... · 2017. 4....

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