Spinal cord injury (SCI) triggers a cascade of pathological events, including persistent neuroinflammation and glial scar formation, which severely hinder axonal regeneration and motor functional recovery. Inspired by the immunosuppressive and regenerative features of the tumor microenvironment, this study introduces a high-reward strategy that repurposes tumor-derived extracellular vesicles (TDEVs) for SCI repair. To ensure localized delivery and enhance safety, TDEVs are incorporated into an injectable adhesive hydrogel composed of carboxymethyl chitosan (CMC) and polydopamine (PDA), crosslinked through Schiff-base chemistry. The resulting TDEVs@CMC-PDA hydrogel adheres firmly to the injured spinal cord and enables sustained release of TDEVs, allowing targeted modulation of the injury microenvironment. In a mouse SCI model, TDEVs@CMC-PDA effectively attenuates neuroinflammation, suppresses glial scar formation, and promotes axonal regrowth and remyelination, ultimately improving motor function. Importantly, biosafety assessments reveal no evidence of systemic toxicity or transcriptional activation of oncogenic pathways. These findings highlight the therapeutic promise and safety of repurposing TDEVs with the adhesive CMC-PDA hydrogel, positioning this strategy as a compelling platform for neural regeneration and beyond.

Glaucoma is a serious cause of permanent blindness worldwide, mainly caused by inflammation and degeneration of the optic nerve. However, current treatments using systemically administered drugs have limited effectiveness due to various biological barriers that prevent their biodistribution in the eye. To overcome these challenges, we developed a new therapy that utilizes intranasal delivery to retinal lesions. In this therapy, we used platelet extracellular vesicles (pEVs) as carriers for epigallocatechin gallate (EGCG), which is known for its neuroprotective, anti-inflammatory, and immunomodulatory properties. We hypothesized that this therapy could overcome ocular barriers, increase drug bioavailability, and mitigate glaucoma progression. We conducted extensive characterization of the biochemical and biophysical properties of the EGCG-pEVs, and the results were promising. In vivo tests using an animal model of dexamethasone-induced glaucoma showed that intranasal administration of EGCG-pEVs was safe and had superior drug delivery and therapeutic efficacy, including anti-inflammatory, immunomodulatory, and intraocular pressure-reducing effects, compared to an intraperitoneal injection or ophthalmic drug administration routes. This unique mode of drug administration shows great potential for clinical applications in ophthalmology.

Vaccination is one of the most effective strategies for preventing infectious diseases. Recently, most research has centered on the development of protein subunit vaccines due to their safety. However, their low immunogenicity remains a challenge. Nanoparticle vaccines offer advantages by protecting proteins from degradation and acting as adjuvants to stimulate the immune system. Herein, a polyplexe (OVA@PEI/Fu) formed by the electrostatic interaction between positively charged polyethyleneimine (PEI) and negatively charged fucoidan was prepared for the encapsulation of a model antigen, ovalbumin (OVA). Experimental results revealed that the incorporation of fucoidan in the polyplexes not only enhanced OVA loading efficiency but also contributed adjuvant effects, significantly boosting dendritic cell activation and maturation in vitro compared to OVA@PEI polyplexes. In vivo experiments showed that the OVA@PEI/Fu can induce strong anti-OVA specific antibody responses, as well as OVA-specific CD4+ and CD8+ T cell responses. The carrier developed in the present study shows promise as a platform for protein-based subunit vaccines.

Damage to lower genitourinary (GU) organs, which can lead to organ dysfunction and/or infertility, poses a significant threat to individual health and quality of life. Polysaccharide-based delivery systems for biologically active therapeutics have emerged as promising strategies for regenerative treatment. However, several challenges remain in achieving site-specific delivery with optimal bioactivity, stability, and sustained release for long-term therapeutic efficacy. This review highlights recent advancements in delivery system design, including manufacturing technologies, bioactive loading strategies, and innovative therapeutic applications aimed at enhancing clinical outcomes. We explore how these developments are being applied to regenerative therapies targeting lower GU injuries and dysfunctions. Notably, the integration of smart delivery technologies, tailored biomaterials, and bio responsive platforms has led to the development of more precise, multifunctional, and intelligent systems. Encouraging results have been reported both in clinical applications and preclinical in vivo models. Furthermore, the continuous evolution of biomedical materials, therapeutic agents, and 3D printing techniques, combined with emerging engineering approaches, offers a promising future for the management and repair of lower GU tract disorders.

Obesity-induced inflammation in visceral adipose tissue (VAT) is a major driver of metabolic dysfunctions, contributing to severe health conditions such as insulin resistance, diabetes, and fatty liver disease. Current anti-inflammatory therapies lack specificity, often leading to systemic immune suppression. To address this challenge, this study develops a nanosilicon-based hydrogen (H2)-generating nanostructure coated with a positively charged copolymer layer, specifically designed for targeted immunomodulation within VAT. Following intraperitoneal administration in high-fat diet-fed obese mice, the positively charged H2-generating nanostructure selectively accumulates in the expanded extracellular matrix of obese VAT through electrostatic attraction to its negatively charged components. Once accumulation, it reacts with body fluids to sustainably generates H2. This continuous H2 release reprograms the local immune microenvironment by balancing pro-inflammatory M1 and anti-inflammatory M2 adipose tissue macrophages, effectively mitigating VAT inflammation and restoring adipocyte function. In addition to its localized effects, this intervention improves systemic lipid and glucose metabolism, highlighting its potential to address obesity-associated metabolic dysfunctions. By targeting VAT inflammation with high specificity and minimal side effects, this H2-based nanotechnology offers a promising therapeutic strategy for obesity and its related metabolic disorders.

Physical stimulation with mild heat possesses the notable ability to induce immunomodulation within the tumor microenvironment (TME). It transforms the immunosuppressive TME into an immune-active state, making tumors more receptive to immune checkpoint inhibitor (ICI) therapy. Transient receptor potential vanilloid 1 (TRPV1), which can be activated by mild heat, holds the potential to induce these alterations in the TME. However, achieving precise temperature control within tumors while protecting neighboring tissues remains a significant challenge when using external heat sources. Taking inspiration from the heat sensation elicited by capsaicin-containing products activating TRPV1, this study employs capsaicin to chemically stimulate TRPV1, imitating immunomodulatory benefits akin to those induced by mild heat. This involves developing a glutathione (GSH)-responsive immunomodulatory prodrug micelle system to deliver capsaicin and an ICI (BMS202) concurrently. Following intravenous administration, the prodrug micelles accumulate at the tumor site through the enhanced permeability and retention effect. Within the GSH-rich TME, the micelles disintegrate and release capsaicin and BMS202. The released capsaicin activates TRPV1 expressed in the TME, enhancing programmed death ligand 1 expression on tumor cell surfaces and promoting T cell recruitment into the TME, rendering it more immunologically active. Meanwhile, the liberated BMS202 blocks immune checkpoints on tumor cells and T cells, activating the recruited T cells and ultimately eradicating the tumors. This innovative strategy represents a comprehensive approach to fine-tune the TME, significantly amplifying the effectiveness of cancer immunotherapy by exploiting the TRPV1 pathway and enabling in situ control of immunomodulation within the TME.

Polysaccharides, with the abundant availability, biodegradability, and inherent safety, offer a vast array of promising applications. Leveraging the remarkable attributes of polysaccharides, biomimetic and multifunctional hydrogels have emerged as a compelling avenue for efficacious wound dressing. The gels emulate the innate extracellular biomatrix as well as foster cellular proliferation. The distinctive structural compositions and profusion of functional groups within polysaccharides confer excellent physical/chemical traits as well as distinct restorative involvements. Gels crafted from polysaccharide matrixes serve as a robust defense against bacterial threats, effectively shielding wounds from harm. This comprehensive review delves into wound physiology, accentuating the significance of numerous polysaccharide-based gels in the wound healing context. The discourse encompasses an exploration of polysaccharide hydrogels tailored for diverse wound types, along with an examination of various therapeutic agents encapsulated within hydrogels to facilitate wound repair, incorporating recent patent developments. Within the scope of this manuscript, the perspective of these captivating gels for promoting optimal healing of wounds is vividly depicted. Nevertheless, the pursuit of knowledge remains ongoing, as further research is warranted to bioengineer progressive polysaccharide gels imbued with adaptable features. Such endeavors hold the promise of unlocking substantial potential within the realm of wound healing, propelling us toward multifaceted and sophisticated solutions.

Due to the mortality associated with thrombosis and its high recurrence rate, there is a need to investigate antithrombotic approaches. Noninvasive site-specific thrombolysis is a current approach being used; however, its usage is characterized by the following limitations: low targeting efficiency, poor ability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms, and risk of thrombus recurrence that is comparable to that of traditional pharmacological thrombolysis agents. Therefore, it is vital to develop an alternative technique that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed. This platform is capable of delivering a synthetic peptide derived from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors for noninvasive site-specific thrombolysis, effective anticoagulation, and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequently rupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancing bioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extended circulation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination can significantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultant phototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor-1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.

Near-infrared–photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole–iron oxide–afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm−1 peaks; substantial O–H stretching was seen, with significant C=C stretching at 1637 cm−1; and a modest appearance of C–O–H bending at 1444 cm−1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.

The exine capsules of pollen particles exhibit a variety of characteristic surface morphologies that promote their cell interactions; their use as antigen carriers for vaccination has been proposed. However, the allergy-causing substances in pollen particles may not all be removed, even by vigorous chemical treatments. To resolve this issue, this work develops systemic approaches for synthesizing pollen-mimetic metal-organic frameworks (MOFs), which comprise aluminum (Al) ions and an organic linker (2-aminoterephthalic acid), with tunable spike-like nanostructures on their surfaces. The as-synthesized MOFs act not only as a delivery vehicle that carries a model antigen (ovalbumin, OVA) but also as an adjuvant (Al). Scanning and transmission electron microscopies images reveal that the aspect ratio of the nanospikes that are grown on the MOFs can be controlled. A higher aspect ratio of the nanospikes on the MOFs is associated with greater cell attachment and faster and more efficient phagocytosis in cells, which results in greater expressions of pro-inflammatory cytokines. Consequently, a more robust immune response against the antigen of interest is elicited. These findings have broad implications for the rational design of the future antigen/adjuvant-presenting particles for vaccination.

Bacteria‐mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium‐like metal–organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side‐effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2‐aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium‐like MOFs under exposure to an near‐infrared laser and the immune checkpoint blockade of systemically administered αPD‐1 is evaluated in tumor‐bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis.

Most cancer vaccines under development are associated with defined tumor antigens rather than with all antigens of whole tumor cells, limiting the anti-tumor immune responses that they elicit. This work proposes an immunomodulator (R848)-loaded nanoparticle system (R848@NPs) that can absorb near-infrared light (+ NIR) to cause low-temperature hyperthermia that interacts synergistically with its loaded R848 to relieve the tumor-mediated immunosuppressive microenvironment, generating robust anti-tumor memory immunity. In vitro results reveal that the R848@NPs could be effectively internalized by dendritic cells, causing their maturation and the subsequent regulation of their anti-tumor immune responses. Post-treatment observations in mice in which tumors were heat-treated at high temperatures reveal that tumor growth was significantly inhibited initially but not in the longer term, while low-temperature hyperthermia or immunotherapy alone simply delayed tumor growth. In contrast, a combined therapy that involved low-temperature hyperthermia and immunotherapy using R848@NPs/ + NIR induced a long-lasting immunologic memory and consequently inhibited tumor growth and prevented cancer recurrence and metastasis. These results suggest that the method that is proposed herein is promising for generating cancer vaccines in situ, by using the tumor itself as the antigen source and the introduced R848@NPs/ + NIR to generate a long-term anti-tumor immunity, for personalized immunotherapy.

Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized aluminum‐based metal–organic framework (Al‐MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast‐derived capsule is used to carry the Al‐MOF‐armored OVA as a “Trojan Horse”‐like transport platform. In vitro experiments reveal that the mineralization of Al‐MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al‐MOFs can gradually disintegrate in a phosphate ion‐containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the “Trojan Horse”‐like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al‐MOF‐armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long‐lasting, high‐levels of mucosal S‐IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.

Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.

Inflammatory bowel disease (IBD) is an intestinal inflammatory disorder. Exogenous hydrogen sulfide (H2S) donors such as diallyl trisulfide (DATS) have been used as anti-inflammatory mediators. However, an ideal method of administering DATS has yet to be established owing to its poor water solubility. Herein, a self-spray coating system that is derived from a DATS-loaded capsule with foaming capability (CAP-w-FC) is proposed for treating colitis. Following the rectal administration of CAP-w-FC into rats bearing colitis and its subsequent dissolution in the intestinal fluid, a spray coating system is self-assembled in situ. This system greatly promotes the dissolution of the poorly water-soluble DATS by producing nano-scaled micellar particles that are sprayed onto the large luminal surface of the colorectal tract. Following the internalization of the micellar particles by colon epithelial cells, their loaded DATS reacts with intracellular glutathione to yield H2S. This exogenous H2S then diffuses through plasma membranes to carry out its biological functions, including suppressing the overproduction of pro-inflammatory cytokines, inhibiting the adhesion of macrophages on the vascular endothelium, and repairing colonic inflamed tissues. Analytical results demonstrate that this self-spray coating system may be used as a unique drug delivery technique for covering the large colorectal surface to treat IBD.

Focal infections that are caused by antibiotic-resistant bacteria are becoming an ever-growing challenge to human health. To address this challenge, a pH-responsive amphiphilic polymer of polyaniline-conjugated glycol chitosan (PANI-GCS) that can self-assemble into nanoparticles (NPs) in situ is developed. The PANI-GCS NPs undergo a unique surface charge conversion that is induced by their local pH, favoring bacterium-specific aggregation without direct contact with host cells. Following conjugation onto GCS, the optical-absorbance peak of PANI is red-shifted toward the near-infrared (NIR) region, enabling PANI-GCS NPs to generate a substantial amount of heat, which is emitted to their neighborhood. The local temperature of the NIR-irradiated PANI-GCS NPs is estimated to be approximately 5 °C higher than their ambient tissue temperature, ensuring specific and direct heating of their aggregated bacteria; hence, damage to tissue is reduced and wound healing is accelerated. The above results demonstrate that PANI-GCS NPs are practical for use in the photothermal ablation of focal infections.

Event Abstract Back to Event Synergistic antibacterial effects mediated by graphene/iron oxide-based nanocomposites Hsing-Wen Sung1, 2*, Wen-Yu Pan1*, Chieh-Cheng Huang1*, Tzu-Tsen Lin1*, Hsin-Yi Hu1*, Wei-Chih Lin1* and Meng-Ju Li3* 1 National Tsing Hua University, Department of Chemical Engineering, Taiwan 2 National Tsing Hua University, Institute of Biomedical Engineering, Taiwan 3 National Taiwan University Hospital Hsinchu Branch, Department of Pediatrics, Taiwan This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe2+/Fe3+ ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. Keywords: Bacteria, temperature, biomedical application, Polymeric material Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in wound care Citation: Sung H, Pan W, Huang C, Lin T, Hu H, Lin W and Li M (2016). Synergistic antibacterial effects mediated by graphene/iron oxide-based nanocomposites. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01627 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Hsing-Wen Sung, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email1 Dr. Wen-Yu Pan, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email2 Dr. Chieh-Cheng Huang, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email3 Dr. Tzu-Tsen Lin, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email4 Dr. Hsin-Yi Hu, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email5 Dr. Wei-Chih Lin, National Tsing Hua University, Department of Chemical Engineering, Hsinchu, Taiwan, Email6 Dr. Meng-Ju Li, National Taiwan University Hospital Hsinchu Branch, Department of Pediatrics, Hsinchu, Taiwan, Email7 Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hsing-Wen Sung Wen-Yu Pan Chieh-Cheng Huang Tzu-Tsen Lin Hsin-Yi Hu Wei-Chih Lin Meng-Ju Li Google Hsing-Wen Sung Wen-Yu Pan Chieh-Cheng Huang Tzu-Tsen Lin Hsin-Yi Hu Wei-Chih Lin Meng-Ju Li Google Scholar Hsing-Wen Sung Wen-Yu Pan Chieh-Cheng Huang Tzu-Tsen Lin Hsin-Yi Hu Wei-Chih Lin Meng-Ju Li PubMed Hsing-Wen Sung Wen-Yu Pan Chieh-Cheng Huang Tzu-Tsen Lin Hsin-Yi Hu Wei-Chih Lin Meng-Ju Li Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.