We know what we are, but know not what we may be.
--- William Shakespeare
Let’s go invent tomorrow instead of worrying about what happened yesterday.
― Steve Jobs
As we look ahead into the next century, leaders will be those who empower others.
― Bill Gates
The blue of the sky is one of the most special colors in the world, because the color is deep but see-through both at the same time.
― Cynthia Kadohata
Impossible is a word to be found only in the dictionary of fools.
--- Napoleon Bonaparte
Everything has beauty, but not everyone sees it.
--- Confucius
Patients deserve more. They deserve not only providing them with best available treatment, follow up and counselling, but they need also to benefit from major advances made in various fields of science and are expected to have impact on medicine in near future. Surgery has always benefited well from advances made in in engineering, imaging, electronics, and computer science for improving understanding of mechanism of disease, developing new techniques for diagnostics, operative tools, postoperative monitoring and interpretation of outcomes of surgery.
Today, the exponential advancements made in the field of communication technologies has brough many, and in a very short time new concepts that were introduced to us but the field was not able to absorb them as fast as these were developed and offered. One possible limitation being the lack of effective flow of information, involvement of clinicians and slowness of the process of introducing new advances in other science disciplines to medical education curricula, training or specialty continuous learning. Therefore, it is mandatory to keep this flow in appropriate pace and continuous especially to specialty of craniomaxillofacial (CMF) surgery through our leading journal, the Journal of Craniofacial Surgery.
To bring things together in a holistic care [1], future therapy will comprise automated smart implants that can function according to need, e.g. release appropriate molecules as needed, take and eliminate others, heal if damaged, etc. To achieve the vision of having autonomous implants, we need to develop implants with not only sensors and actuators but also with communication capabilities. Through connecting to the Internet of Things (IoTs) and the hardware and software tools available in cloud, smart devices will be independent with no need for interference from us. This development will take stages, 1) development of implants with smart components, 2) development of implants that can be controlled by doctors and specialized care givers, 3) development of implants that can be controlled by patients and at last autonomous implants, with native tissue or organ mimicking properties ad behavior.
To accomplish this, developments in biomaterials that currently include “smartness” such as memory, responsiveness and self-healing have been made. The other aspect of smartness in implants is sensing. Developments in sensing include the monitoring of various physiological variables that involve vital signs as well as disease biomarkers via nanoscale implantable, targeted devices or wearable devices. Another aspect of development comprises the microrobots that can be injected into the body, propelling towards a problem area and perform microsurgery. Researchers have already demonstrated the use of such robots for patching small wounds in the stomach, remove dangerous objects, and deliver drugs to tumors.
To coordinate these devices and interpret the data that they are collecting, developments in communications include both novel communication techniques such as molecular communication as well as novel networking concepts such as Internet of Bio-NanoThings (IoBNTs) geared towards the realization of smart and connected healthcare [2]. IoBNTs envisions the heterogeneous collaborative networks of natural and artificial nano-biological functional devices (e.g., engineered bacteria, human cells and nanobiosensors), seamlessly integrated to the internet infrastructure. IoBNTs is positioned to extend our connectivity and capability to have control over non-conventional domains (e.g., human body) with unprecedented spatiotemporal resolution, enabling paradigm-shifting applications in the healthcare domain, such as continuous health monitoring with autonomous implants and therapeutic systems with single molecular precision.
Advances made in the miniaturization of devices helps to develop micro- and nanoscale implants which can process sensor signals on the device and make decisions to actuate on the spot according to preprogrammed embedded rules. Novel technologies such as the application-specific integrated circuits (ASIC) and microelectromechanical systems (MEMS) are utilized to build the physical sensor components and the electronics to control them at very small scales. Besides electronics-based devices, bioengineering provides alternative device technologies based on engineering of natural cells and molecules. Engineered bacteria and stem cells, synthetic cells, and functional biomolecules such DNA, protein, nanoparticles can be considered as devices capable of sensing, actuating, and reporting similar to conventional devices but with an inherent biocompatibility. Even processing of data is possible by synthetic biology which created examples of logic circuits implemented in cells with genetic modification. Moreover, since cells already have their mechanisms to provide energy for cellular functions, powering these biology-based devices does not present an issue as it is the case for electronics-based devices. To address the latter, energy harvesting and wireless power delivery have been developed to build stand-alone devices without any tethers. Energy harvesting in the body for smart implants can be achieved using piezoelectric materials which convert kinetic energy in the form of vibrations or shocks into electrical energy. Alternatively, energy can be harvested by using antennae to capture power delivered wirelessly from electromagnetic waves sent from outside the body. Usually, wireless power delivery is coupled with wireless data transmission where the electromagnetic wave sent to implanted device captures the wave, use it to power up its components and backscatter the wave to send back data similar to principles of radiofrequency identification (RFID) tags that are currently used in everyday life.
Considering the plethora of biomedical devices implanted or dwelling in various organs in the body, their small size limits their spatial operation range. Therefore, establishing communication among these devices within an organ will allow them to execute complex tasks that they cannot accomplish alone. A concerted effort of these devices requires not only communication between similar types of devices focusing on a collective goal in an organ, but also communication with other device clusters in related organs, and communication with wearables on the surface of the body which will eventually relay information to devices outside of the body. This information transfer chain will allow remote interrogation and reconfiguration of implantable and wearable devices and processing of collected information by fusing data acquired from different types of sensors and from different spatio-temporal conditions. Due to small size, implantable microdevices often lack powerful signal processing hardware and software. Hence, relaying the information to outside of the body enables the use of advanced hardware tools to run complicated algorithms such as machine learning routines which are shown to be very effective to extract clinical decisions from noisy sensor data.
Connecting ubiquitous smart implants in the body to the internet, it becomes possible to create massive data sets for longitudinal and horizontal studies that can help physicians to get a more complete picture of a single patient’s health at a granular level at all times and also compare and contrast data from numerous patients outside of clinical settings. Since current implantable and wearable medical devices have limited access to body health parameters, it is not possible to concoct such a database which may eventually be of service for early diagnosis of diseases, monitoring of conventional therapies, and autonomous therapies. A challenge that arises here is that we cannot, as care givers process this huge amount of data. Therefore, the use of artificial intelligence will enable us to interpret collected data and make appropriate decisions after being trained using accumulated clinical data, which may eventually help to develop autonomous implants.
It is also interesting but challenging to be able to pick-up natural communications taking place in the body in the form of biochemical signals at the molecular level and transduce them to electrical signals that could be communicated outside. This novel concept called molecular communication, which involves the propagation of information encoded on the properties of molecules such as concentration, type and timing by a transmitter that emits molecular signals in the environment [3]. On the other end, a receiver captures these molecules by chemical receptors and recovers the intended information. Molecular communication envisions to enable devices and organ systems to be connected to the internet to form networks of natural cells and man-made devices, i.e. IoBNTs, where implants can get information they need, deal with problems autonomously and report anomalies to healthcare professionals [4].
Molecular Communication can be complemented with other technologies enabling communication of implants with devices outside of the body. Terahertz (THz) communication (electromagnetic waves with frequency between radiofrequency and optical waves) is a promising candidate since the implant antenna size for that frequency is in the nanoscale range. However, at THz frequencies, communication signal is attenuated by water molecules (70% of body is water), which limits the depth a signal can penetrate. Another alternative is to use ultrasound waves, but large-size acoustic transducers are needed, which is a limiting factor.
IoBNT envisions the use of large number of devices to be connected, which creates challenges for the management of IoBNT network. The first challenge is the transduction of molecular to electrical signals, which need to be processed and forwarded. These are called bio-cyber gateways and they connect biological realm with the electronics realm. These gateways can be built by using miniaturized electrochemical sensors having biorecognition elements and optical sensor hosting reporter cells. Another challenge is the change in the location or growth of the tissue, which can be overcame by using smart and biodegradable materials The other challenge is the security and privacy of this network, since health data is very critical, and any attack can have adverse effects on patient’s health. Cyber-security addresses this problem by creating physical signatures using unique electrical conductivity characteristics of one’s body as authentication which cannot be replicated by another individual.
These technologies together, will ultimately lead to a paradigm shift for surgery far more significant than the shift from open surgery to minimally-invasive surgeries. Applications based on the interconnected implants surpass their individual capabilities to enable unprecedented resolution of sensing, minimally invasive tools to perform microscale surgery without any incisions, and continuous monitoring of healing and recovery.
Accordingly, smart implants will ultimately be the self-healing body that will be part of wide grid of connect computer-bodies that interact, learn from each other experiences, advise, communicate and actuate. Our healing and remodeling capabilities in our bodies will be vastly expanded to an unprecedented limit. We will be able to be a part of the overall “syncytium” of the existence around us. Act and interact. At some stage such independent autonomous system, will need only minor interference forms for adjustment, maintenance and possible updating. These tasks are mainly to be undertaken by engineers jointly with surgeons or alone, and new specialties will emerge that combine both engineering and medicine to be able to deal with these challenges where interventions can be through the IoTs and not only through knife and sutures. At this point in time surgery would have done much of its mission in shaping a new face of the future through new capabilities at the level of molecules and energy waves.
Acknowledgements
The authors acknowledge that they have no competing interests. The authors also acknowledge funding from National Institutes of Health (1UG3TR003148-01) and the American Heart Association (18TPA34230036, 442611-NU80922), U.S. National Science Foundation under Grant CNS-17663969.
References
- [1].Ashammakhi N, Darabi MA, Pountos I, The Dynamic Cycle of Future Personalized and Regenerative Therapy, Journal of Craniofacial Surgery 30(3) (2019) 623–625. [DOI] [PubMed] [Google Scholar]
- [2].Akyildiz IF, Pierobon M, Balasubramaniam S, Koucheryavy Y, The internet of bio-nano things, IEEE Communications Magazine 53(3) (2015) 32–40. [Google Scholar]
- [3].Akan OB, Ramezani H, Khan T, Abbasi NA, Kuscu M, Fundamentals of molecular information and communication science, Proceedings of the IEEE 105(2) (2016) 306–318. [Google Scholar]
- [4].Akyildiz IF, Chen J, Ghovanloo M, Guler U, Ozkaya-Ahmadov T, Pierobon M, Sarioglu AF, Unluturk BD, Microbiome-Gut-Brain Axis as a Biomolecular Communication Network for the Internet of Bio-NanoThings, IEEE Access 7 (2019) 136161–136175. [Google Scholar]