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Journal Club Theme of March 2016: When mechanics meets medicine in the new age

Shaoxing Qu's picture

Shaoxing Qu

Department of Engineering Mechanics, Zhejiang University, China

Introduction

Mechanics and medicine are two “classic”, but seemingly disconnected branches of science. Mechanics describes the mechanical behavior (i.e., motion, deformation, and etc.) of a physical body when subjected to forces or displacement, while medicine is the science and practice related to health and illness. As mechanicians, we are proud of theories and methods of mechanics for their numerous contributions to human civilization ranging from civil infrastructures to machines to even electronics. However, the role of mechanics in medicine should not be ignored, such as describing the mechanical behavior of the various components in the biological body, and assisting clinic and internal medicine surgery directly or indirectly. Recently, the fast development of science and technology leads to more involvement of mechanics in medicine and vice versa. 

Mechanical behavior of tissues and organs

Mechanics problems associated with fracture of bones and teeth, blood flow in vessels, beat of hearts and etc. have been studied extensively in our society. Recently, biomaterials for repairing and regenerating tissues and organs attract researchers from mechanics, polymer, biomedicine, etc. Hydrogel, soft and wet, is one typical soft biomaterial for biomedical applications, such as drug delivery, extra-cellular matrix, and tissue engineering matrices [1]. Hydrogel is taken as the only candidate for the artificial soft tissues (cartilage, muscle, tendon, and ligament) [2]. The mechanical performances of the hydrogel as soft tissues requires high toughness, low friction, a certain strength, and high deformability. To overcome the brittleness and weakness of the conventional hydrogels, Double-network hydrogels with enhanced strength and toughness were discovered and developed in which a high relative molecular mass neutral polymer is incorporated within a swollen heterogeneous network [3]. Highly stretchable and toughness double-network hydrogel of ionically and covalently crosslinked network was developed, assisted by knowledge of mechanics [4]. A strategy to design tough bonding of hydrogels to non-porous hard surfaces was achieved to mimic the tough interface of the bonding of tendon and cartilage to bone in biological bodies [5].

Mechanics in advanced medical devices

Medical devices are necessary in modern clinical medicine for the purpose of prevention, diagnosis, treatment, monitoring, or alleviation of disease or injury. During the past decade, quite a few mechanics research groups, in collaboration with people from other disciplines, have been successfully developed flexible and/or stretchable electronics to be used in modern clinical medicine, for example, flexible and high-density brain electrode array [6], electronic sensor and actuator webs [7], ultra-flexible piezoelectric devices integrated with heart as energy harvester [8], dielectric elastomer peristaltic pump [9], wearable electrode for electrocardiography using nanomaterials following the bottom-up approach [10], electronic dura mater [11], syringe-injectable electronics [12], bioresorbable silicon electronic sensors for the brain [13], etc.. Knowledge of mechanics is applied to design the special structures, as well as to determine the proper locations for the electronic elements.

Challenges and opportunities

Advance of new technologies paves the way for mechanics to play a more important role in medicine, from diagnosis and treatment of illness to prevention and restore from disease. Moreover, mechanics can act as the bridge for the interdisciplinary research between engineering and medicine, which may promote the renaissance of mechanics.

1.To characterize and develop more accurate constitutive models for various biological tissues and organs. For modern clinical medicine, quantitative relationship between the deformation of a tissue or organ and the pathological signal is required for diagnosis of illness. Therefore, the deformation response of a tissue or organ subjected to external stimuli such as pressure should be accurately predicted, leading to the development of novel constitutive relationships. 

2.To explore pathological mechanisms. Many injuries and failures of the tissues and organs are closely related to their strength and toughness, and occurring with complicated environment. Proper mechanics models to be developed are necessary for revealing the relevant pathological mechanisms, which is useful for both prevention and treatment of illness.

3.To design novel medical devices. Modern clinical medicine calls for more intelligent medical devices, including stents, brain electrodes, medical sensors, tonometers, medical robots, etc.. For example, besides biocompatibility and robustness, a stent requests the smooth transition from flexible state during implantation to firm one after the surgery, as well as consistence with fluid dynamics. Analytical, computational and experimental studies based on the theories and methods in mechanics will contribute considerably to the design of novel medical devices.

References

1. A. S. Hoffman, “Hydrogels for biomedical applications,” Advanced Drug Delivery Reviews, 43, 3-12, 2002.

2. J. P. Gong, “Why are double network hydrogels so tough,” Soft Matter, 6, 2583-2590, 2010.

3. J. P. Gong, Y. Katsuyama, T. Kurokawa, Y. Osada, “Double-network hydrogels with extremely high mechanical strength,” Advanced Materials, 15, 1155-1158, 2003. 

4. J. Y. Sun, X. H. Zhao, W. R. K. Illeperuma, et al., “Highly stretchable and tough hydrogels,” Nature, 489, 133-136.

5. H. Yuk, T. Zhang, S. T. Lin, et al., “Tough bonding of hydrogels to diverse non-porous surfaces,” Nature Materials, 15, 190-196, 2016.

6. J. Viventi, D. H. Kim, L. Vigeland, et al., “Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo,” Nature Neuroscience, 14, 1599-U138, 2011.

7. D. H. Kim, R. Ghaffari, N. S. Lu, et al., “Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy,” Proceedings of The National Academy of Sciences of The United States of America, 109, 19910-19915, 2012.

8. B. W. Lu, Y. Chen, D. P. Ou, et al., “Ultra-flexible Piezoelectric Devices Integrated with Heart to Harvest the Biomechanical Energy,” Scientific Reports, 5, 16065, 2015.

9. G. Y. Mao, X. Q. Huang, J. J. Liu, et al., “Dielectric elastomer peristaltic pump module with finite deformation,” Smart Materials and Structures, 24, 075026, 2015.

10. C. Myers, H. Huang, Y. Zhu, “Wearable silver nanowire dry electrodes for electrophysiological sensing,” RSC Advances, 5, 11627-11632, 2015.

11. I. R. Minev, P. Musienko, A. Hirsch, et al, “Electronic dura mater for long-term multimodal neural interfaces,” Science, 347, 159-163, 2015.

12. J. Liu, T. M. Fu, Z. G. Cheng, et al., “Syringe-injectable electronics,” Nature Nanotechnology, 10, 629-636, 2015.

13. S. K. Kang, R. K. J. Murphy, S. W. Hwang, et al., “Bioresorbable silicon electronic sensors for the brain,” Nature, 530, 71-79, 2016.

Shaoxing Qu's picture

This post is very general.  Welcome comments and discussions for specific direction.

Bin Liu's picture

Shaoxing,  thanks for sharing this perspective of mechanics in this field. I have learned a lot from this post.

Shaoxing Qu's picture

Bin, Thanks! 

Thanks for initiating this discussion!  I think Drug Design is also an interesting medicine-related topic where

 our mechanicial can contribute a lot. In some sense, Drug Design is intended to find some configurations in the

design space which have global mimimum energies. This means that some energy minimization approaches well

developed in mechanics can also be used for Drug Desig.  Of course, the total energy function involved in a  Drug Desig problem is a highly non-linear and most of importamt of all a highly non-convex function of the generalized coordinates.

Therefore finding global optimum is very difficult and theoretically a NP-hard problem. But any advnacement along this

direction will also be very helpful for the solution of  many complex mechanics problems, e.g., post-buckling analysis, the propagation of crack, damage evolution, which can also be viewed as energy minimizaton processes.

 

 

 

Dear Xu Guo,

 

thank you for pointing out the drug design. Can you give some more details and some references to this field?

 

Thanks Bafty

Shaoxing Qu's picture

Xu, Drug Design assisted by energy minimization is a very inspiring topic! We look forward to publications in this field coming soon.

ChangyongCao's picture

Dear Shaoxing,

Thank you very much for the excellent introduction and inspiring discussion. There are great opportunities in combing mechanics and medicine to address the grand challenges that we are facing today. Here, I would like to share our recent study on developing a novel fouling-release urinary catheter [1]. Catheter-associated urinary tract infections are the most common cause of hospital-acquired infections and there are over 30 million Foley urinary catheters used annually in the USA. The catheters will readily acquire biofilms when inserted into human body, and can be clogged by the biofilms in a short time. Current available strategies, such as killing bacteria or delaying bacterial attachment, to reduce the related infection have been unsuccessful in the long-term prevention of biofilm formation. 

In this work, we proposed a new design and optimization of urinary catheter capable of on-demand removal of biofilms based on the theory and method in mechanics. The urinary catheters utilized 4 intra-wall inflation lumens that were pressure-actuated to generate region-selective strains in the elastomeric urine lumen, and thereby remove overlying biofilms (Fig.1). It was demonstrated that the catheter prototypes were able to remove greater than 80% of a mixed community biofilm of P. mirabilis and E. coli on-demand, and furthermore were able to remove the biofilm repeatedly for long-term use. In addition, thanks to the compatibility with current industry standard and materials, the cost would only rise 50 cents per catheter based on our estimation with the venders. This new fouling-release catheter offers the potential for an efficient, non-biologic, non-antibiotic method to remove biofilms. 

Best,

Changyong

 

[1] V. Levering*, C. Cao*, P. Shivapooja, H. Levinson, X. Zhao, G.P. López. Urinary catheter capable of repeated on-demand removal of infectious biofilms via active deformation, Biomaterials 77, 77-86, 2016.

Shaoxing Qu's picture

Changyong, great work! Traditional mechanics of materials focused on strength and ductility of "hard"  materials. Recently, researchers pay more attendtion to the functionality of "soft" materials such as the biofilm in your work. Advance in new technology of medicine is amazing, which discloses more problems related to health and illniess that can be solved by people from mechanics and other disciplines. Would you like to share your experience on collaborating with colleagues from medicine related field? 

It is an interesting thought. Indeed, biomechanics is quite promising.

Shaoxing Qu's picture

Bin, thanks! Any other comments or suggestions based on your work in biomechanics?

Yonggang Huang's picture

Thanks for this interesting post.  Indeed mechanics may play an important role in medicine as Shaoxing has pointed out.  On the first point "Mechanical behavior of tissues and organs" Shaoxing discussed, in addition to the fundamental understanding, there may also be important application opportunities.  For example, if some important phisiological parameters (e.g., hydration level) can be correlated to mechanical properties (thermal conductivity, elastic modulus) then the non-invasive measurement of the latter may provide an easy and straightforward way to determine the former.

On the second point "Mechanics in advanced medical devices" Shaoxing mentioned, I fully agree with his view, but want to emphasize that this needs to be done in close collaboration  with the scientists and engineers including materials science, electrical engineering, biomedical engineering, and of course, medicine.

Shaoxing Qu's picture

 Yonggang, your comments and suggestions are excellent!

Yong Zhu's picture

Thanks, Shaoxing, for leading the discussion on this very interesting topic. Also thanks, Yonggang, for pointing out the opportunities. We have done some work recently in the two areas mentioned.   

On the first point "Mechanical behavior of tissues and organs", we have developed a strain sensor that can monitor the large strain associated with the motions of human joints. The sensor exhibits excellent linearity and repeatability. Using this sensor, we can monitor a wide range of human motions from finger movement to patellar reflex to walking, running and jumping. Due to the soft nature of the sensor, it might find use in measuring mechanical behavior of tissues and organs.   

 

On the second point "Mechanics in advanced medical devices", we recently developed a stretch-trigged method for drug delivery, in collaboration with a group in biomedical engineering. Tensile strain was found to significantly promote the drug delivery. Sustained release by daily motions of muscles, tendons and bone joints can thus be achieved in a convenient manner. Simple analyses attributed the promotion of drug delivery to the enlarged surface area for diffusion and Poisson's ratio-induced compression on the drugs, which, however, need much more work. 

Yong Zhu's picture

S. Yao and Y. Zhu, "Wearable multifunctional sensors using printed stretchable conductors made of silver nanowires", Nanoscale 6, 2345-2352 (2014).  

J. Di, S. Yao, Y. Ye, J. Yu, Z. Cui, T. Ghosh, Y. Zhu, Z. Gu,"Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots", ACS Nano 9 (9), 9407–9415 (2015).

Sulin Zhang's picture

Thanks to Shaoxing for this exciting post. Indeed there is plenty of room at the interface of mechanics and biology. Some of mechanicians, including Subra Suresh (CMU), Gang Bao (Rice), Jimmy Hsia (CMU), Taher Saif (UIUC), etc. have delved into the field at different stages of their careers, all with great success. The problems generally require coordinated inputs from different disciplines to make a complete story, and thus more challenging, as commented by Yonggang. 

My group in recent years made some attempts in this field. Besides some earlier work in understanding the cellular uptake of nanoparticles (size selective, shape senstive, and microenvironment regulative), we move slowly toward mechanics of multicellular structures and mechanics in phathology. For instance, we recently explained why red blood cells become very stiff at the asexual stage of malaria infection:

 

 Zhang Y.*, Huang C. J.*, Kim S., Golkaram M.*, Dixon M. W. A., Tilley L., Li J., Zhang S. L.◊, Suresh S. Multiple stiffening effects of nanoscale knobs on malaria parasite-infected human red blood cells, Proceedings of National Academy of Sciences, 12, 6068-6073, (2015).

 

And why red blood cells exhibit reverible stiffness during the sexual stage of malaria infection, ready to re-transmit the disease by mosquitos:

 

    Megan K. Dearnley#, Chu Thi Thu Trang#, Yao Zhang#, Oliver Looker#, Changjin Huang, Nectarios Klonis, Jeff Yeoman, Shannon Kenny, Mohit Arora, James Osborne,Rajesh Chandramohanadas, Sulin Zhang, Matthew W.A. Dixon and Leann Tilley. Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages. Proceedings of National Academy of Sciences. In print, 2016.  

Shaoxing Qu's picture

Sulin, thanks a lot for the comment! Your work posted here is very inspiring.

Henry Tan's picture

Shaoxing,

This is a nice topic and sorry for being late in replying. Recently I am working on surface roughness induced implant-associated infection, a case involving both mechanics and medical devices, a recent paper is published in Journal of the Mechanics and Physics of Solids, in press.

Title: In vivo surface roughness evolution of a stressed metallic implant

Abstract: Implant-associated infection, a serious medical issue, is caused by the adhesion of bacteria to the surface of biomaterials; for this process the surface roughness is an important property. Surface nanotopography of medical implant devices can control the extent of bacterial attachment by modifying the surface morphology; to this end a model is introduced to facilitate the analysis of a nanoscale smooth surface subject to mechanical loading and in vivo corrosion. At nanometre scale rough surface promotes friction, hence reduces the mobility of the bacteria; this sessile environment expedites the biofilm growth. This manuscript derives the controlling equation for surface roughness evolution for metallic implant subject to in-plane stresses, and predicts the in vivo roughness changes within 6 hours of continued mechanical loading at different stress level. This paper provides analytic tool and theoretical information for surface nanotopography of medical implant devices.

-- Henry

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