Hydrogel facilitated bioelectronic integration.

The recent advances in bio-integratable electronics are creating new opportunities for investigating and directing biologically significant processes, yet their performance to date is still limited by the inherent physiochemical and signaling mismatches at the heterogeneous interfaces. Hydrogels represent a unique category of materials to bridge the gap between biological and electronic systems because of their structural/functional similarity to biological tissues and design versatility to accommodate cross-system communication. In this review, we discuss the latest progress in the engineering of hydrogel interfaces for bioelectronics development that promotes (1) structural compatibility, where the mechanical and chemical properties of hydrogels can be modulated to achieve coherent, chronically stable biotic-abiotic junctions; and (2) interfacial signal transduction, where the charge and mass transport within the hydrogel mediators can be rationally programmed to condition/amplify the bioderived signals and enhance the electrical/electrochemical coupling. We will further discuss the application of functional hydrogels in complex physiological environments for bioelectronic integration across different scales/biological levels. These ongoing research efforts have the potential to blur the distinction between living systems and artificial electronics, and ultimately decode and regulate biological functioning for both fundamental inquiries and biomedical applications.

Comparing Gut Microbiome in Mothers' Own Breast Milk- and Formula-Fed Moderate-Late Preterm Infants.

Gut microbiome plays an important role in adult human health and diseases. However, how nutritional factors shape the initial colonization of gut bacteria in infants, especially in preterm infants, is still not completely known. In this study, we compared the effects of feeding with mothers' own breast milk (MBM) and formula on the initial composition and gene expression of gut bacteria in moderate-late preterm infants. Fecal samples were collected from ten formula-fed and ten MBM healthy infants born between 32 and 37 weeks' gestation after they reached full-volume enteral feedings. Total DNAs were extracted from fecal samples for amplicon sequencing of 16S ribosomal RNA (rRNA) gene and total RNA with rRNA depletion for metatranscriptome RNA-Seq 16S rRNA gene amplicon sequencing results showed that the alpha-diversity was similar between the MBM- and formula-fed preterm infants, but the beta-diversity showed a significant difference in composition (p = 0.002). The most abundant taxa were Veillonella (18.4%) and Escherichia/Shigella (15.2%) in MBM infants, whereas the most abundant taxa of formula-fed infants were Streptococcus (18.6%) and Klebsiella (17.4%). The genera Propionibacterium, Streptococcus, and Finegoldia and order Clostridiales had significantly higher relative abundance in the MBM group than the formula group, whereas bacteria under family Enterobacteriaceae, genera Enterococcus and Veillonella, and class Bacilli were more abundant in the formula group. In general, microbiomes from both diet groups exhibited high functional levels of catalytic activity and metabolic processing when analyzed for gene ontology using a comparative metatranscriptome approach. Statistically, the microbial genes in the MBM group had an upregulation in expression related to glycine reductase, periplasmic acid stress response in Enterobacteria, acid resistance mechanisms, and L-fucose utilization. In contrast, the formula-fed group had upregulations in genes associated with methionine and valine degradation functions. Our data suggest that the nutritional source plays a role in shaping the moderate-late preterm gut microbiome as evidenced by the differences in bacterial composition and gene expression profiles in the fecal samples. The MBM group enriched Propionibacterium. Glycine reductase was highly upregulated in the microbiota from MBM along with the upregulated acid stress tolerance genes, suggesting that the intensity of fermentation process was enhanced.

Bottom-Up Construction of Electrochemically Active Living Filters: From Graphene Oxide Mediated Formation of Bacterial Cables to 3D Assembly of Hierarchical Architectures.

Living composites comprising of both biotic and abiotic modules are shifting the paradigm of materials science, yet challenges remain in effectively converging their distinctive structural and functional attributes. Here we present a bottom-up hybridization strategy to construct functionally coherent, electrochemically active biohybrids with optimal mass/charge transport, mechanical integrity, and biocatalytic performance. This biohybrid can overcome several key limitations of traditional biocarrier designs and demonstrate superior efficiency in metabolizing low-concentration toxic ions with minimal environmental impact. Overall, this work exemplifies a biointegration strategy that complements existing synthetic biology toolsets to further expand the range of material attributes and functionalities.

Modularized Field-Effect Transistor Biosensors.

Field-effect transistors (FETs), when functionalized with proper biorecognition elements (such as antibodies or enzymes), represent a unique platform for real-time, specific, label-free transduction of biochemical signals. However, direct immobilization of biorecognition molecules on FETs imposes limitations on reprogrammability, sensor regeneration, and robust device handling. Here we demonstrate a modularized design of FET biosensors with separate biorecognition and transducer modules, which are capable of reversible assembly and disassembly. In particular, hydrogel "stamps" immobilizing bioreceptors have been chosen to build biorecognition modules to reliably interface with FET transducers structurally and functionally. Successful detection of penicillin down to 0.25 mM has been achieved with a penicillinase-encoded hydrogel module, demonstrating effective signal transduction across the hybrid interface. Moreover, sequential integration of urease- and penicillinase-encoded modules on the same FET device allows us to reprogram the sensing modality without cross-contamination. In addition to independent bioreceptor encoding, the modular design also fosters sophisticated control of sensing kinetics by modulating the physiochemical microenvironment in the biorecognition modules. Specifically, the distinction in hydrogel porosity between polyethylene glycol and gelatin enables controlled access and detection of larger molecules, such as poly-l-lysine (MW 150-300 kDa), only through the gelatin module. Biorecognition modules with standardized interface designs have also been exploited to comply with additive mass fabrication by 3D printing, demonstrating potential for low cost, ease of storage, multiplexing, and great customizability for personalized biosensor production. This generic concept presents a unique integration strategy for modularized bioelectronics and could broadly impact hybrid device development.

Hydrogel Gate Graphene Field-Effect Transistors as Multiplexed Biosensors.

Nanoscale field-effect transistors (FETs) represent a unique platform for real time, label-free transduction of biochemical signals with unprecedented sensitivity and spatiotemporal resolution, yet their translation toward practical biomedical applications remains challenging. Herein, we demonstrate the potential to overcome several key limitations of traditional FET sensors by exploiting bioactive hydrogels as the gate material. Spatially defined photopolymerization is utilized to achieve selective patterning of polyethylene glycol on top of individual graphene FET devices, through which multiple biospecific receptors can be independently encapsulated into the hydrogel gate. The hydrogel-mediated integration of penicillinase was demonstrated to effectively catalyze enzymatic reaction in the confined microenvironment, enabling real time, label-free detection of penicillin down to 0.2 mM. Multiplexed functionalization with penicillinase and acetylcholinesterase has been demonstrated to achieve highly specific sensing. In addition, the microenvironment created by the hydrogel gate has been shown to significantly reduce the nonspecific binding of nontarget molecules to graphene channels as well as preserve the encapsulated enzyme activity for at least one week, in comparison to free enzymes showing significant signal loss within one day. This general approach presents a new biointegration strategy and facilitates multiplex detection of bioanalytes on the same platform, which could underwrite new advances in healthcare research.

Potential applications of image-guided radiotherapy for radiation dose escalation in patients with early stage high-risk prostate cancer.

Patients with early stage high-risk prostate cancer (prostate specific antigen > 20, Gleason score > 7) are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical-free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT), by virtue of combining the steep dose gradient of intensity-modulated radiotherapy and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypo-fractionated IGRT and it may improve patient quality of life.

Effectiveness of radiotherapy for elderly patients with non-melanoma skin cancer of the head.

AIM: To assess the effectiveness of conventionally fractionated radiotherapy for local control and cosmesis in elderly patients (age 70 years or older) with non-melanoma skin cancer of the head. METHODS: A retrospective review of 15 patients undergoing definitive radiation (11 patients) or postoperative radiation (4 patients) for squamous cell carcinoma (9 patients) and basal cell carcinoma (6 patients) of the head was undertaken. At each follow-up visit, a radiation oncology resident and/or medical student was requested to examine the patient's head and neck, and determine the initial location of the cancer without reviewing their medical record. RESULTS: No patient developed a loco-regional recurrence. The residents and medical students were unable to determine the initial location of the cancer because of the skin normalcy. CONCLUSION: Conventionally fractionated radiotherapy is effective for local control and provides excellent cosmesis for elderly patients with skin cancer of the head.

Feasibility of tomotherapy for postoperative irradiation of lower extremity sarcomas.

AIMS AND BACKGROUND: To evaluate the effectiveness of helical tomotherapy-based image-guided radiotherapy (IGRT) following surgery for lower extremity sarcoma. METHODS AND STUDY DESIGN: A retrospective review of three patients undergoing postoperative irradiation with tomotherapy for lower extremity sarcoma was conducted. Planning target volume (PTV) coverage, acute side effects, long-term complications and functional results were assessed. RESULTS: Tomotherapy allows adequate coverage of the PTV without an excessive radiation dose to the normal adjacent structures. Radiotherapy side effects were acceptable with no treatment breaks. All patients were disease free with no complications and no impairment of their daily activity at the last follow-up. CONCLUSION: IGRT delivered by tomotherapy may be ideally suited for sarcoma of the extremities because of its ability to achieve a high radiation dose along with excellent normal tissue sparing. Further prospective studies should be conducted to confirm this hypothesis.

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer.

BACKGROUND: In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. METHODS: A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). RESULTS: At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. CONCLUSIONS: IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. METHODS: A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. RESULTS: At a median follow-up of 22 months (4-53 months), no patient developed retropharyngeal nodal recurrences. CONCLUSION: Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Effectiveness of intensity-modulated and image-guided radiotherapy to spare the mandible from excessive radiation.

We would like to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) to decrease the risk of osteoradionecrosis in locally advanced head and neck cancer. We conducted a retrospective study of 83 patients with head and neck cancer undergoing concurrent definitive chemoradiation, post-operative radiotherapy or chemoradiation, or radiotherapy alone with IMRT or IGRT. Mean mandibular dose was, respectively, 43.6Gy and 43.8Gy for the IMRT and IGRT technique. At a median follow-up of 28 months (5-55 months), only one patient developed osteoradionecrosis requiring hyperbaric oxygen. Sharp dose falloff associated with IMRT and IGRT decreased excessive radiation of the mandible and may reduce the risks of osteoradionecrosis.

Feasibility of tomotherapy to reduce cochlea radiation dose in patients with locally advanced nasopharyngeal cancer.

AIMS AND BACKGROUND: To evaluate the effectiveness of tomotherapy-based image-guided radiotherapy (IGRT) on the radiation dose to the cochlea in patients with nasopharyngeal cancer. METHODS AND STUDY DESIGN: A retrospective review of five patients undergoing concurrent chemoradiation with tomotherapy for locally advanced nasopharyngeal cancer was performed. RESULTS: The mean dose to the right and left cochlea was 25 Gy and 35.3 Gy respectively, while the dose to the gross tumor ranged from 70 to 75 Gy. All patients had excellent clinical response to the treatment at a median follow-up of five months. CONCLUSIONS: IGRT for head and neck cancer delivered by tomotherapy can significantly decrease the radiation dose to the cochlea without sacrificing target volume coverage.

Feasibility of image-guided radiotherapy based on tomotherapy for the treatment of locally advanced anal carcinoma.

BACKGROUND: The standard of care for locally advanced anal cancer has been concurrent chemoradiation. However, conventional treatment with 3-dimensional radiotherapy is associated with significant toxicity. The feasibility of new radiotherapy techniques such as image-guided radiotherapy (IGRT) in combination with chemotherapy for the treatment of this malignancy was assessed. PATIENTS AND METHODS: A retrospective review of five patients with locally advanced anal carcinoma treated with Tomotherapy-based IGRT was conducted. All the patients received concurrent chemotherapy. RESULTS: Gastrointestinal toxicity remained the limiting factor as four patients experienced grade 3-4 enteritis requiring a break during treatment. No patient experienced grade 3-4 hematological toxicity. Despite the large tumor size, three patients achieved local control at a median follow-up of 19 months. CONCLUSION: Tomotherapy-based IGRT may be a promising treatment for locally advanced anal cancer and needs to be investigated in further prospective trials.