1 Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai 519087, China; nc.ude.unb.liam@317930119102 (Y.W.); nc.ude.unb.liam@580930119102 (Y.H.)
Find articles by Yue Wang1 Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai 519087, China; nc.ude.unb.liam@317930119102 (Y.W.); nc.ude.unb.liam@580930119102 (Y.H.)
Find articles by Yu Huang2 College of Electronic Engineering, Heilongjiang University, Harbin 150080, China; nc.ude.ujlh@80iygnohiab
Find articles by Hongyi Bai3 College of Microelectronics, Shenzhen Institute of Information Technology, Shenzhen 518172, China; nc.ude.tiizs@qggnaw
Find articles by Guoqing Wang4 Research Center for Advanced Optics and Photoelectronics, Department of Physics, College of Science, Shantou University, Shantou 515063, China; nc.ude.uts@3uhhx
Find articles by Xuehao Hu5 Shandong Key Laboratory of Optical Communication Science and Technology, School of Physics Science and Information Technology, Liaocheng University, Liaocheng 252059, China; nc.ude.ucl@hsotnas
Find articles by Santosh Kumar1 Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai 519087, China; nc.ude.unb.liam@317930119102 (Y.W.); nc.ude.unb.liam@580930119102 (Y.H.)
Find articles by Rui Min1 Center for Cognition and Neuroergonomics, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University at Zhuhai, Zhuhai 519087, China; nc.ude.unb.liam@317930119102 (Y.W.); nc.ude.unb.liam@580930119102 (Y.H.)
2 College of Electronic Engineering, Heilongjiang University, Harbin 150080, China; nc.ude.ujlh@80iygnohiab
3 College of Microelectronics, Shenzhen Institute of Information Technology, Shenzhen 518172, China; nc.ude.tiizs@qggnaw
4 Research Center for Advanced Optics and Photoelectronics, Department of Physics, College of Science, Shantou University, Shantou 515063, China; nc.ude.uts@3uhhx
5 Shandong Key Laboratory of Optical Communication Science and Technology, School of Physics Science and Information Technology, Liaocheng University, Liaocheng 252059, China; nc.ude.ucl@hsotnas
* Correspondence: nc.ude.unb@nimiur Received 2021 Oct 19; Accepted 2021 Nov 20. Copyright © 2021 by the authors.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
This article discusses recent advances in biocompatible and biodegradable polymer optical fiber (POF) for medical applications. First, the POF material and its optical properties are summarized. Then, several common optical fiber fabrication methods are thoroughly discussed. Following that, clinical applications of biocompatible and biodegradable POFs are discussed, including optogenetics, biosensing, drug delivery, and neural recording. Following that, biomedical applications expanded the specific functionalization of the material or fiber design. Different research or clinical applications necessitate the use of different equipment to achieve the desired results. Finally, the difficulty of implanting flexible fiber varies with its flexibility. We present our article in a clear and logical manner that will be useful to researchers seeking a broad perspective on the proposed topic. Overall, the content provides a comprehensive overview of biocompatible and biodegradable POFs, including previous breakthroughs, as well as recent advancements. Biodegradable optical fibers have numerous applications, opening up new avenues in biomedicine.
Keywords: biocompatible, biodegradable, polymer optical fiber, biomedical applicationSince the 1990s, optical fiber systems have been widely used in data transmission due to advancements in laser, optical fiber amplifier, and optical fiber technology [1]. With advantages such as no radiation, immunity to electromagnetic interference (EMI), and ease of multiplexing [2], optical-fiber-based technology is becoming more prevalent in a variety of sectors of our lives, including communication [3,4], microwave generation [5,6], mechanical inspection [6,7], and earthquake early warning [7,8]. Silica optical fiber is the backbone of the global Internet, with wavelengths optimized between 1260 and 1650 nm and typically employing single-mode fiber (SMF) with a core diameter of 4~8 μm [9]. Only one mode propagates in SMF, resulting in a faster transmission speed and greater distance than multimode silica optical fiber. The core diameter of a multimode silica optical fiber is typically 50 or 62.5 μm, which enables the propagation of multiple light modes within the optimized communication window of 850 nm and 1300 nm [10,11]. Silica optical fiber transmission ranges can be customized by adding impurities, such as doping materials. Additionally, there are various diameters of silica multimode optical fiber for use in specialized sensing applications [12,13]. Due to the numerous advantages, conventional silica optical fibers are widely used in sensors [12,14,15,16], high-energy military weapons [17], high-speed internet communications, and cloud-based data services [18,19,20]. While silica optical fibers have gained significant attention and value in medical applications, such as endoscopes [21], optical coherence tomography (OCT), and heart rate monitors [22], they are intrinsically stiff and, therefore, cannot provide the required flexibility and biocompatibility for biomedical applications. Due to their fragility and susceptibility to bending or distortion, the high risk of fracture may adversely impact the user’s safety when implanted in tissues or attached to the skin. Additionally, once a silica optical fiber is implanted beneath the skin, the incompatibility of its mechanical and chemical properties results in blood–material interface adhesion, foreign-body and infectious reaction, chronic inflammation, and tissue damage [23].
Polymer optical fibers (POFs) are optical fibers made of polymer optical materials throughout. For short-range visible light transmission, conventional polymer optical fibers are made of PMMA with core diameters of 980 μm or 735 μm [24,25]. A PMMA POF has an optical attenuation of 0.15 dB/m near 650 nm, which is three orders of magnitude greater than that of a standard silica optical fiber (0.2 dB/km at 1550 nm). However, because POF has a larger numerical aperture (NA) than standard telecommunications-grade silica optical fiber, they are more convenient to connect and install, making them attractive for short-distance connectivity applications, such as fiber-to-the-home (FTTH) and healthcare systems [26]. The first and most widely used polymer optical fiber communication medium was PMMA. With the advancement of optical fiber technology, AGC (formerly known as Asahi Glass Co.) now retails several varieties of CYTOP-based graded-index polymer optical fiber (GI-POF) under the trade name “Fontex”. This type of optical fiber has a double cladding structure and exhibits low attenuation and scattering losses due to the absence of the CH bond and a low refractive index. Unlike the POFs mentioned previously, the small-dimensional “Fontex” is transparent between 650 and 1300 nm and exhibits virtually minimal transmission loss. Additionally, it is more resistant to bending than conventional silica fiber, allowing for optical transmission through knots on fiber without disconnection [20]. Thus, “Fontex” is a type of optical fiber that is both reliable and safe for high-speed and large-volume data transmission. Additionally, polymer optical fibers are advantageous for sensing applications. For instance, researchers have discovered POFs’ extraordinary sensing capability, which includes pressure, humidity, temperature, and vibration [27,28,29].
Apart from the well-known applications mentioned previously, optical fibers have been used in medicine for decades, providing a safer and more efficient method of disease diagnosis, health monitoring [30], and clinical treatment [31,32]. With the development of advanced medical instruments in recent years, some optical fibers have found commercial applications in medical applications, and growing research is focusing on this promising technique. Compared with the conventional silica optical fiber, POFs possess many other advantages, such as lower Young’s modulus (~3.2 GPa for PMMA), higher failure strain, and better flexibility. The small size, low cost, nontoxicity, and electromagnetic insensitivity of biocompatible POFs make them ideal for devices applied in or near the body that shed some light on novel therapies in immunology, cardiology, neurology, oncology, and gastroenterology, among other fields [33,34,35]. For example, it is reported that wearable optical fiber based on fiber Bragg gratings can be used to monitor heart rate [36] and detect basic activities, such as walking, sitting, and squatting [15], which is promising for chronic disease prevention. Due to the increasing prevalence of diseases such as cancer, lithiasis, and angiocardiopathy, as well as the growth of minimally invasive surgery, there is an urgent need for more biocompatible, more photoconductive, and less invasive optical fibers, as well as nontoxic, tissue-like materials and low-cost, high-productivity, and versatile fabrication methods. In recent years, one has seen a surge in the use of polymer optical fibers due to their high elastic strain limit, flexibility, ease of manipulation, and low cost.
It is worth noting that a portion of biocompatible polymers are biodegradable, meaning they can be hydrolyzed or degraded into small molecules in a physiological environment [37,38]. As a result, it can further minimize damage to the host tissues, as additional removal surgery is not required. Natural materials are the best candidates for biocompatible and biodegradable optical fibers due to their superior optical and mechanical properties, nontoxicity, and intrinsic biodegradability that is proportional to the number of different components. Biocompatible optical fibers have been developed using protein, agarose, silk and spider fiber, cellulose, and cells [2,39,40,41]. In that, the bacteria-cell-based optical fiber exhibits the best biocompatibility and biodegradability due to its tissue-like nature. Synthetic polymers, such as poly (ethylene glycol) (PEG), poly (glycolic acid) (PGA), aliphatic polyesters of poly (lactic acid) (PLA), poly (lactic-co-glycolic acid) (PLGA), and poly (L-lactic acid) (PLLA), have been approved by the U.S. Food and Drug Administration (FDA) for medical applications, such as biosensing, drug delivery, and tissue engineering [42,43,44,45,46,47]. Along with low light attenuation and excellent transparency, this type of optical fiber has a low Young’s modulus and a high degree of flexibility, which allows it to be less cytotoxic and invasive to surrounding tissues. Hydrogel-based optical fibers are a research focus due to their porous structure and high water content that is compatible with the extracellular matrix [48]. This type of optical fiber is reported to have an excellent tensile strength of up to 2.27 Mpa, the ability to stretch more than nine times its original length, and the ability to self-heal [49]. Additionally, hydrogel optical fibers can remain functional for a controllable period of time in a physiological fluid environment after being implanted into free-moving mice [50]. Hydrogels perform poorly in comparison to polyesters and other thermoplastics in terms of optical properties and fabrication operability [38]. However, coating hydrogels on thermoplastic polymer fibers appears to be an ideal solution for tissue damage mitigation, as it softens the surface of the fibers and mimics the water content of the tissue. The advancement of medicine, particularly neuroscience, has increased the demand for multifunctional optical fibers, as the activities of cells or organs are influenced by the co-ordination of multiple signals, such as chemical signals, electrical signals, and neurotransmitters [51,52]. Multifunctional optical fibers allow for the integration of waveguides, microfluidic channels, and electrodes, enabling simultaneous interrogation of chemical, mechanical, and electrical signals without significant invasion. More precisely, they are capable of deep tissue delivery of drugs, nutrients, and viral vectors via hollow channels [53,54].
Many articles and reviews have been written about biocompatible and biodegradable optical fibers, that have become a hot research topic and are rapidly developing in recent years. In 2018, Nazempour, R. et al. published an overview on the development of bio-compatible and implantable optical fibers and waveguides for biomedicine, which included a good number of examples and illustrations, clear organization, and expression, as well as informative discussion and outlooks [55]. Gierej, A. et al. presented a systematic review of fabrication processes and discussed issues that may influence them, such as biomaterial properties and other considerations [56].
In this review, we focus on the differences between optical fiber and waveguide that have been overlooked in the majority of previous reviews. In addition, to keep this article focused and well-organized, we only use biocompatible and biodegradable optical fibers made of polymers. It is worth noting that we treated biomaterials, optical fiber fabrication methods, and their biomedical applications equally in order to make our review informative and appropriate for anyone seeking a thorough understanding of the topic. We present our article in an instructive and logical manner that is useful for researchers who want a broad perspective on the subject and also for readers who do not have a thorough understanding of the topic. We also summarize a number of informative tables and conclusive diagrams to enrich the article. Finally, the content provides a broad overview of biocompatible and biodegradable POFs, including earlier breakthroughs, as well as recent advancements. Section 2 divides constituent materials into five categories: natural materials, hydrogels, synthetic materials, elastomers, and multi-materials. We summarize the optical and mechanical properties, advantages, and limitations of each material using a variety of common and advantageous optical fibers as examples. Because some chemicals appear visually similar, we provide skeletal formulas in addition to their physical and chemical properties to highlight the differences between them. Section 3 focuses on the most commonly used biocompatible and biodegradable optical fiber fabrication methods, such as thermal drawing, casting, extrusion, and other approaches derived from extrusion. In this section, we will go over the fabrication steps, precautions, benefits, and drawbacks of each fabrication method in detail. Section 4 summarizes the critical applications of biocompatible and biodegradable optical fibers in medicine, such as sensing, phototherapy, neural recording, drug delivery, and optogenetics. In the conclusion, we clearly and concisely summarize the benefits and drawbacks of biocompatible and biodegradable POF. Although biocompatible and biodegradable optical fibers perform worse than silica optical fibers in terms of light-guiding efficiency, and there are challenges in complex structure fabrication methods and minimally invasive implanting surgery, biocompatible and biodegradable optical fibers have a bright future in biomedicine. Figure 1 shows a summary of this review about biocompatible and biodegradable polymer optical fibers.