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Page 20 of 39 Yang et al. Soft Sci. 2025, 5, 46 https://dx.doi.org/10.20517/ss.2025.44

et al. prepared a fiber-optic sensor based on a nanocomposite hydrogel loaded with AuNPs in a PBA-based
hydrogel matrix, which exhibited excellent sensitivity, a fast response time (30 s), and a detection limit of
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1 mm .

Blood oxygen and other biomarkers
Blood oxygen levels and various biomarkers serve as critical indicators of physiological health and disease
status. By leveraging flexible optical waveguides, researchers have developed innovative techniques for real-
time, noninvasive monitoring, paving the way for personalized healthcare interventions. Deng et al.
described a highly sensitive hemoglobin detection method based on polarization-differential
spectrophotometry with excellent detection accuracy and sensitivity [Figure 7E ], which can be applied to
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[177]
the early diagnosis of diseases . Similarly, Rahad et al. performed hemoglobin concentration
[178]
measurements using a novel RI nanosensor based on a metal-insulator-metal (MIM) waveguide . Luo
et al. fabricated a reflective fiber-optic sensor for hemoglobin detection using the mechanism by which
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hemoglobin binds to oxygen and is converted to oxyhemoglobin and SPR theory . In brain science
research, Zheng et al. detected neurotransmitters in the micromolar range using a surface-enhanced Raman
[46]
spectroscopy (SERS)-active neural probe based on a tapered fiber (TF), as shown in Figure 7F . To meet
the needs of personalized medicine, Safaee et al. proposed an optical core-shell microfiber textile containing
single-walled carbon nanotubes (SWCNTs) for real-time optical monitoring of the hydrogen peroxide
concentration in in vitro wounds .
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Biomedical therapy
Biomedical therapeutic applications of flexible optical waveguides leverage the unique properties of photons
through photochemical or photophysical mechanisms. These mechanisms encompass a spectrum of
techniques, including photothermal therapy (PTT), photodynamic therapy (PDT), photobiomodulation
(PBM), and optogenetic therapy. The integration of flexible optical waveguides enhances the efficacy and
safety of these therapeutic modalities by facilitating targeted light delivery to specific anatomical sites with
minimal invasiveness . In this section, the diverse applications of flexible optical waveguides in
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biomedical therapy are explored, highlighting their role in advancing therapeutic interventions for various
diseases and medical conditions.

Photomedicine
Currently, phototherapy for cancer consists mainly of PTT and PDT. In PTT, the conversion of light energy
into heat is used to selectively target and destroy cancer cells . Flexible optical waveguides can precisely
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deliver the necessary light to tumor sites, minimizing damage to surrounding healthy tissues and enhancing
treatment specificity. PDT involves the use of light-activated photosensitizers to produce reactive oxygen
species that can kill cancer cells or pathogens [183,184] . The use of flexible optical waveguides in PDT allows
accurate delivery of light to deep tissues, improving the effectiveness and precision of the therapy. An
upconversion nanoparticle (UCNP) is the ideal wireless transducer for PDT, converting near-infrared light
that penetrates deep tissues into visible light for phototherapy. As shown in Figure 8A, Teh et al. developed
a biocompatible UCNP implant delivered in flexible hydrogel optical waveguides . The system was
[48]
successful in achieving chronic PDT in an unfettered and noninvasive manner in a mouse model of
glioblastoma. The application of photomedicine treatments in deep tissues is often challenging because of
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the possible risk of hyperthermia (damage to normal tissues) . Recently, Chen et al. prepared a
temperature-adaptive hydrogel fiber-based optical waveguide (THFOW) [Figure 8B], which can eliminate
deep tumor cells through thermally modulated interventional photomedicine . According to the study
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results, the THFOW showed good light propagation properties and thermal sensitivity along with soft tissue
affinity and was effective in eliminating tumor cells and reducing the risk of overheating in a mouse model.