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Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing.

Background Gas forming infection of the spine is a consequence of vertebral osteomyelitis, necrotizing fasciitis, or a gas-forming epidural abscess, which is very rare and fatal conditions. This is the rare case of necrotizing fasciitis that rapidly progressed from the lumbar area to upper thoracic area. Case presentation A 58-year-old male complained of lower back pain with fever and chills. The patient had a history of uncontrolled diabetes mellitus without diabetic medication over the previous 3 months, and he had received several local injections around the lumbar area. Laboratory data revealed white blood cell count of 19,710 /mm3, erythrocyte sedimentation of 40 mm/h, and C-reactive protein of 30.7 mg/L. Radiological findings revealed a small amount of air bubbles in the paraspinal area and lumbar epidural spaces. The patient refused emergency surgery and was discharged from the hospital. The patient re-visited the emergency department two days after discharge complaining of more severe back pain with persistent fever, and his vital signs had deteriorated, with low blood pressure and tachycardia. K. pneumoniae was isolated in cultures from ultrasound-guided aspirates and peripheral blood. The follow-up radiographs revealed aggressive dissemination of innumerable air bubbles from the lumbar area to the T5 level. The patient underwent emergent decompressive laminectomy and debridement of infected paravertebral fascia and musculature. Despite intensive care for deteriorated vital signs and his back wound, the patient died on postoperative day 3 due to multi-organ failure. Conclusions Necrotizing fasciitis involving the spine is a very rare disease with life-threatening conditions, rapid progression, and a high mortality rate. Therefore, prompt surgical treatment with a high index of suspicion is imperative to prevent potentially fatal conditions in similar extremely rare cases.

Catechol-containing hydrogels have been exploited in biomedical fields due to their adhesive and cohesive properties, hemostatic abilities, and biocompatibility. Catechol moieties can be oxidized to o-catecholquinone, a chemically active intermediate, in the presence of oxygen to act as an electrophile to form catechol-catechol or catechol-amine/thiol adducts. To date, catechol cross-linking chemistry to fabricate hydrogels has been mostly performed at room temperature. Herein, we report large increases in catechol cross-linking reaction kinetics by the freeze-thawing process. The formation of ice crystals during freezing steps spatially condenses catechol-containing polymers into nearly frozen (yet unfrozen) regions, resulting in decreases in the polymeric chain distances. This environment allows great increases in catechol cross-linking kinetics, a phenomenon that can also occur during thawing steps. The increased cross-linking rate and spatial condensation in the cryogels provide unique wall and pore structures, which result in elastic, spongelike hydrogels. The moduli of the cryogels prepared by glycol-chitosan-catechol (g-chitosan-c) were improved by 3-6-fold compared to room temperature-cured conventional hydrogels, and the degree of improvement increased depending on the freezing time and the number of freeze-thawing cycles. Unlike typical cell encapsulations before cross-linking, which have often been a source of cytotoxicity, the macroporosity of cryogels allows nontoxic cell seeding with ease. This research offers a new way to utilize catechol cross-linking chemistry by freeze-thawing processes to simultaneously regulate mechanical strength and porous structures in catechol-containing hydrogels.

Cancer remains one of the most deadly diseases globally, but carbon-based nanomaterials have the potential to revolutionize cancer diagnosis and therapy. Advances in nanotechnology and a better understanding of tumor microenvironments have contributed to novel nanotargeting routes that may bring new hope to cancer patients. Several low-dimensional carbon-based nanomaterials have shown promising preclinical results; as such, low-dimensional carbon dots (CDs) and their derivatives are considered up-and-coming candidates for cancer treatment. The unique properties of carbon-based nanomaterials are high surface area to volume ratio, chemical inertness, biocompatibility, and low cytotoxicity. It makes them well suited for delivering chemotherapeutics in cancer treatment and diagnosis. Recent studies have shown that the CDs are potential applicants in biomedical sciences, both as nanocarriers and nanotransducers. This review covers the most commonly used CD nanoparticles in nanomedicines intended for the early diagnosis and therapy of cancer.

Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp2 carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and in vivo cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.

Recently, there has been growing interest in replacing severely damaged salivary glands with artificial salivary gland functional units created in vitro by tissue engineering approaches. Although various materials such as poly(lactic-co-glycolic acid), polylactic acid, poly(glycolic acid), and polyethylene glycol hydrogels have been used as scaffolds for salivary gland tissue engineering, none of them is effective enough to closely recapitulate the branched structural complexity and heterogeneous cell population of native salivary glands. Instead of discovering new biomaterial candidates, we synthesized hyaluronic acid-catechol (HACA) conjugates to establish a versatile hyaluronic acid coating platform named "NiCHE (nature-inspired catechol-conjugated hyaluronic acid environment)" for boosting the salivary gland tissue engineering efficacy of the previously reported biomaterials. By mimicking hyaluronic acid-rich niche in the mesenchyme of embryonic submandibular glands (eSMGs) with NiCHE coating on substrates including polycarbonate membrane, stiff agarose hydrogel, and polycaprolactone scaffold, we observed significantly enhanced cell adhesion, vascular endothelial and progenitor cell proliferation, and branching of in vitro-cultured eSMGs. High mechanical stiffness of the substrate is known to inhibit eSMG growth, but the NiCHE coating significantly reduced such stiffness-induced negative effects, leading to successful differentiation of progenitor cells to functional acinar and myoepithelial cells. These enhancement effects of the NiCHE coating were due to the increased proliferation of vascular endothelial cells via interaction between CD44 and surface-immobilized HAs. As such, our NiCHE coating platform renders any kind of material highly effective for salivary gland tissue culture by mimicking in vivo embryonic mesenchymal HA. Based on our results, we expect the NiCHE coating to expand the range of biomaterial candidates for salivary glands and other branching epithelial organs.

Here, in Ppara−/− mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12−/−) mice using RNA-guided endonuclease. Acot12−/− mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA., Increasing evidence suggested that dysregulation in lipid metabolism is linked to OA pathogenesis, but the underlying regulatory mechanism is not well understood. Here, the authors show that PPARα-ACOT12 signalling regulates cartilage homeostasis by regulating de novo lipogenesis in mice.

(1) Background: Lumbar spinal stenosis (LSS) causes uncomfortable neuropathic symptoms, which can negatively affect osteoporosis. The aim of this study was to investigate the effect of LSS on bone mineral density (BMD) in patients treated with one of three oral bisphosphonates (ibandronate, alendronate and risedronate) for initially diagnosed osteoporosis. (2) Methods: We included 346 patients treated with oral bisphosphonates for three years. We compared annual BMD T-scores and BMD increases between the two groups according to symptomatic LSS. The therapeutic efficacies of the three oral bisphosphonates in each group were also evaluated. (3) Results: Annual and total increases in BMD were significantly greater in group I (osteoporosis) compared to group II (osteoporosis + LSS). The total increase in BMD for three years was significantly greater in the ibandronate and alendronate subgroups than that in the risedronate subgroup (0.49 vs. 0.45 vs. 0.25, p < 0.001). Ibandronate showed a significantly greater increase in BMD than that of risedronate in group II (0.36 vs. 0.13, p = 0.018). (4) Conclusions: Symptomatic LSS may interfere with the increase in BMD. Ibandronate and alendronate were more effective in treating osteoporosis than risedronate. In particular, ibandronate was more effective than risedronate in patients with both osteoporosis and LSS.

The incidence of snapping popliteus tendon syndrome, a type of lateral knee snapping, is not high, so making an accurate diagnosis is difficult. A proper treatment following an accurate diagnosis is essential for improvement. Very few cases have been reported of its treatment.An 18-year-old male patient had experienced painful popping in the lateral part of the knee during knee flexion for 3 years before his hospital visit.Snapping popliteus tendon syndrome.The patient underwent an all-arthroscopic surgery. Tendon debulking and tissue debridement around the popliteus tendon was conducted, but the snapping did not resolve. The enlarged tubercle was excised through an arthroscopic procedure using a burr, and the surgery was finished after confirming that snapping was resolved.Full range of motion (ROM) was recovered 6 weeks after surgery and the snapping did not recur.Snapping popliteus tendon syndrome is a disease that is hardly recognized due to its low prevalence and difficulty in diagnosis, and it requires close observation of the patient before surgery. The location of the tenderness and the snapping occurrence must also be carefully identified. Our procedure is an entirely arthroscopic technique; as it has the prominent advantage of a speedy recovery and easy rehabilitation, it could also be helpful to set treatment standards for this disease in the future.

Carbon dot-based composite materials have been extensively developed for versatile biomedical applications, such as drug delivery, tissue engineering, bioimaging, biosensors, and photothermal cancer therapy, owing to their excellent mechanical properties, electrical and thermal conductivity, large surface-to-volume ratio, and biocompatibility. For instance, the hydrophobicity and delocalized π-electrons of carbon dots enable insoluble drug loading in carbon composite-based drug delivery carriers. In addition, carbon dot-based materials are suitable for optical and electrochemical biosensor applications owing to their intrinsic properties. Thus, this review briefly focuses on the following: (1) general aspects, (2) various sources, and (3) versatile biomedical applications of carbon dots and composite materials. More importantly, we present the emerging applications of carbon dot-based materials, such as in agricultural systems, COVID-19 theranostics, counterfeit, and security.

Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed biomaterials can surpass the capabilities of their parent material. Herein, the modification of hyaluronic acid (HA) to exhibit self-healing properties is described, and its physical and biological function both in vitro and in vivo is studied. The in vitro findings showed that self-healing HA designed to undergo self-repair improves lubrication, enhances free radical scavenging, and attenuates enzymatic degradation compared to unmodified HA. Longitudinal imaging following intraarticular injection of self-healing HA shows improved in vivo retention despite its low molecular weight. Concomitant with these functions, intraarticular injection of self-healing HA mitigates anterior cruciate ligament injury-mediated cartilage degeneration in rodents. This proof-of-concept study shows how incorporation of functional properties such as self-healing can be used to surpass the existing capabilities of biolubricants.

Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed biomaterials could surpass the capabilities of their parent material. Herein, we describe the modification of hyaluronic acid (HA) molecules to exhibit self-healing properties and studied its physical and biological function both in vitro and in vivo. Our in vitro findings showed that self-healing HA designed to undergo autonomous repair improved lubrication, enhanced free radical scavenging, and resisted enzymatic degradation compared to unmodified HA. Longitudinal imaging following intra-articular injection of self-healing HA showed improved in vivo retention despite the low molecular weight. Concomitant with these functions, intra-articular injection of self-healing HA mitigated anterior cruciate ligament injury-mediated cartilage degeneration in rodents. This proof-of-concept study shows how incorporation of functional properties like self-healing can be used to surpass the existing capabilities of biolubricants.

Mussel-inspired adhesive materials have received much attention for biomedical applications primarily because of their underwater/tissue adhesive properties. However, so far, no comparative study focusing on effect of charge differences (i.e., positive vs. negative) in the presence of conjugated catechols has been conducted. In this study, we investigate the physicochemical characteristics and in vitro/in vivo tissue adhesive properties of hydrogels that use anionic (i.e., hyaluronic acid) and cationic (i.e. chitosan) catechol-conjugated polysaccharides. Fe(III) is utilized to effectively prepare both hydrogels. Hyaluronic acid-catechol (HA-C) hydrogels are immediately formed by iron-catechol coordination bonds, while chitosan-catechol (CHI-C) hydrogel is formed by both iron-catechol coordination and catechol-amine covalent reactions. The gelation time and in vitro adhesiveness are similar for both CHI-C and HA-C hydrogels. Differences are found in that the CHI-C hydrogels showed enhanced water-resistance and long-lasting adhesion in vivo. It is noteworthy to mention that the cationic nature of mussel adhesive proteins due to lysine and histidine residues in the pads of Mytilus edulis is known to be an important contributor to underwater adhesion. Thus, this comparative study provides significant insight for the design of effective mussel-inspired adhesive materials.

Purpose: Various surgical methods have been reported for Kummell’s disease with neurologic deficits. The aim of this study was to introduce long-segmental posterior fusion (LPF) combined with vertebroplasty (VP) and wiring as an alternative surgical technique. Material and Methods: We retrospectively analyzed 10 patients undergoing posterior decompression and LPF combined with VP and wiring for Kummell’s disease with neurologic deficits from January 2011 to December 2014. The radiologic outcomes included the local kyphotic angle (LKA) and vertebral wedge angle (VWA). Clinical outcomes, including the visual analog scale (VAS), the Oswestry Disability Index (ODI) and the Frankel grade were assessed. Surgery-related complications were also evaluated. Results: The mean age of the included patients was 77 ± 8 years with a mean follow-up period of 31.4 ± 4.9 months and a mean bone mineral density of −3.5 ± 0.7 (T-score). The mean operation time was 220 ± 32.3 minutes with a mean blood loss of 555 ± 125.7 mL. The preoperative LKA and VWA were significantly corrected postoperatively (37.9 ± 8.7° vs. 15.3 ± 5.3°, p = 0.005 for LKA; 21.3 ± 5.1° vs. 7.6 ± 2.8°, p = 0.005 for VWA) without a loss of correction at the last follow-up. The VAS and ODI were also significantly improved (7.7 ± 1.1 vs. 3.0 ± 1.6, p = 0.007 for VAS; 90.3 ± 8.9 vs. 49.6 ± 22.7, p = 0.007 for ODI). The Frankel grade of all patients was improved by at least 1 or 2 grades at the last follow-up. Surgery-related complications such as intraoperative cement leakage and implant loosening during the follow-up were not observed. Conclusions: LPF combined with VP and wiring might be an effective surgical option for Kummell’s disease with neurologic deficits, especially for the elderly patients with morbidities. Level of Evidence: level IV.

Embryonic salivary gland mesenchyme (eSGM) secretes various growth factors (bioactives) that support the proper growth and differentiation of salivary gland epithelium. Therefore, eSGM cells can be used as feeder cells for in vitro-cultured artificial salivary gland if their survival and bioactivity are properly maintained. As eSGM is encapsulated in a hyaluronan (HA)-rich developmental milieu, we hypothesized that mimicking this environment in vitro via surface immobilization of HA might enhance survival and bioactivity of eSGM. In this study, various HA derivatives, conjugated with catechol (HA–CA), thiol (HA–SH), or amine (HA–EDA) moieties, respectively, were screened for their efficacy of culturing eSGM-derived feeder cells in vitro. Among these HA derivatives, HA–CA showed the highest surface coating efficiency and growth enhancement effect on the embryonic submandibular gland. In addition, the HA–CA coating enhanced the production of growth factors EGF and FGF7, but not FGF10. These effects were maintained when eSGM cells isolated from the embryonic salivary gland were re-seeded to develop the feeder layer cells. CD44s (a major HA receptor) in eSGM cells were clustered at the cell membrane, and enhanced EGF expression was detected only in CD44 cluster-positive cells, suggesting that membrane clustering of CD44 is the key mechanism for the increased expression of EGF.

All animal experiments for evaluating drug efficacy or developing medical devices are unavoidably accompanied by bleeding that result in unreliable outcomes with large variations between individuals. Herein, we developed hemostatic swabs prepared by a mussel-inspired catecholamine polymer called chitosan-catechol, which was inspired by the chemical composition of the well-known material-independent coating material of polydopamine. The hemostatic ability of the swabs resulted from the formation of self-sealing membranes by rapid intermolecular interactions between whole blood proteins and the applied chitosan-catechol. The blood protein/chitosan-catechol composite sealing membrane resulted in dramatic decreases in bleeding for both normal and coagulopathic models, such as diabetes.

Rationale: Unilateral diaphragmatic paralysis due to cervical spondylosis has rarely been reported. We present the first case of unilateral diaphragmatic paralysis without radicular pain or motor weakness due to cervical foraminal stenosis and a review of the related literature. Patient concerns: A 59-year-old man presented with dyspnea and fever. His chest radiograph revealed right hemidiaphragmatic paralysis. Diagnoses: The differential diagnosis of phrenic nerve palsy excluded mediastinal and neurodegenerative diseases. Imaging studies showed right foraminal stenosis caused by cervical spondylosis at C3–4 and C4–5. Interventions: The patient underwent foraminotomy at C3–4 and C4–5 on the right side. The operative findings revealed a severe compression of the C4 root. Outcomes: At 3 months postoperatively, the unilateral diaphragmatic paralysis and dyspnea were recovered. Lessons: Hemidiaphragmatic paralysis deserves careful evaluation for the presence of cervical spondylosis, even without concomitant neurologic manifestations.

Background Charcot spinal arthropathy, also known as Charcot spine and neuropathic spinal arthropathy, is a progressive and destructive condition that affects an intervertebral disc and the adjacent vertebral bodies following loss of spinal joint innervation. We report the first case of Charcot spinal arthropathy (CSA) associated with cerebrospinal fluid (CSF)-cutaneous fistula. Case presentation A 54-year-old male who underwent T10-L2 posterior instrumented spinal fusion seven years prior for treatment of T11 burst fracture and accompanying T11 complete paraplegia visited our department complaining of leakage of clear fluid at his lower back. The patient had also undergone various types of skin graft and myocutaneous flap surgeries for treatment of repetitive pressure sores around his lumbosacral area. The patient presented with persistent CSF leakage from a cutaneous fistula (CSF-cutaneous fistula) formed in a lumbosacral pressure sore. The CSF-cutaneous fistula arose from the L5 post-traumatic CSA. Surgery was planned for management of CSF-cutaneous fistula and post-traumatic L5 CSA. We successfully treated the CSF-cutaneous fistula with ligation and transection of the dural sac and cauda equina at the L2-L3 level. In addition, the post-traumatic L5 CSA was successfully treated with a posterior four-rod spinopelvic fixation from T9 to ilium and S2 foramina. After surgery, the CSF leakage stopped and no other adverse neurological changes were found. The four-rod spinopelvic construct was well maintained five years later. Conclusions CSA associated with CSF-cutaneous fistula is a very rare disorder. Only surgical treatment for both CSA and CSF-cutaneous fistula with ligation and transection of the dural sac and posterior four-rod spinopelvic fixation can bring satisfactory results.

This report describes a simple method to prepare water-soluble chitosan derivative by conjugation of an enediol group, catechol. Chitosan functionalized with a catechol-containing compound, 3,4-dihydroxyhydrocinnamic acid, by a carbodiimide coupling method resulted in chitosan–catechol conjugates. This one-step chemical modification of high-molecular-weight chitosan (approximately 100 kDa) dramatically increased the water solubility of the chitosan derivative to 60 mg mL−1 at pH 7.0. The degree of catechol conjugation was found critical in determining the solubility. The chitosan–catechol conjugates are not only water-soluble but are adhesive, due to the intrinsic adhesive properties of catechol. Also, the water-soluble chitosan derivative allows one to directly form chitosan hydrogel in neutral buffer solutions. The utility of both the water solubility and the adhesive property of the chitosan–catechol was demonstrated by the effective layer-by-layer assembly on substrates. The water-soluble chitosan–catechol is expected to be useful in many areas of surface functionalization, drug delivery, tissue engineering, and tissue adhesives.

Mussel-inspired adhesion chemistry provides a useful alternative to the use of fibrin glues., Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

Dry mouth, or xerostomia, caused by salivary gland dysfunction significantly impacts oral/systemic health and quality of life. Although in vitro-generated artificial salivary glands have been considered as the fundamental solution, its structural complexity is difficult to reproduce using current biomaterials. Therefore, understanding and recapitulating the roles of biomacromolecules in salivary gland organogenesis is needed to solve these problems. Hyaluronic acid (HA) is a macromolecule abundant during salivary gland organogenesis, but its role remains unknown. Here, we verify the effects of HA on salivary gland organogenesis and artificial organ germ formation in solubilized and substrate-immobilized forms. In embryonic submandibular glands (eSMG), we found dense HA layers encapsulating proliferative c-Kit+ progenitor cells that were expressing CD44, an HA receptor. The blockage of HA synthesis, or degradation of HA, impaired eSMG growth by ablating the c-Kit+ progenitor cell population. We also found that high-molecular-weight (HMW) HA has a significant role in eSMG growth. Based on these findings, we discovered that HA is also crucial for in vitro formation of salivary gland organ germs, one of the most promising candidates for salivary gland tissue regeneration. We significantly enhanced salivary gland organ germ formation by supplementing HMW HA in solution; this effect was further increased when the HMW HA was immobilized on the substrate by polydopamine/HA co-immobilization. Our study suggests that the current use of HA in salivary gland tissue engineering can be further optimized.

Practical lithium metal batteries require full and reversible utilization of thin metallic Li anodes. This introduces a fundamental challenge concerning how to create solid-electrolyte interphases (SEIs) that are able to regulate interfacial transport and protect the reactive metal, without adding appreciably to the cell mass. Here, we report on physicochemical characteristics of Langmuir–Blodgett artificial SEIs (LBASEIs) created using phosphate-functionalized reduced graphene oxides. We find that LBASEIs not only meet the challenges of stabilizing the Li anode, but can be facilely assembled in a simple, scalable process. The LBASEI derives its effectiveness primarily from its ability to form a durable coating on Li that regulates electromigration at the anode/electrolyte interface. In a first step towards practical cells in which the anode and cathode capacities are matched, we report that it is possible to achieve stable operations in both coin and pouch cells composed of a thin Li anode with the LBASEI and a high-loading intercalation cathode.

Polydopamine is one of the simplest and most versatile approaches to functionalizing material surfaces, having been inspired by the adhesive nature of catechols and amines in mussel adhesive proteins. Since its first report in 2007, a decade of studies on polydopamine molecular structure, deposition conditions, and physicochemical properties have ensued. During this time, potential uses of polydopamine coatings have expanded in many unforeseen directions, seemingly only limited by the creativity of researchers seeking simple solutions to manipulating surface chemistry. In this review, we describe the current state of the art in polydopamine coating methods, describe efforts underway to uncover and tailor the complex structure and chemical properties of polydopamine, and identify emerging trends and needs in polydopamine research, including the use of dopamine analogs, nitrogen-free polyphenolic precursors, and improvement of coating mechanical properties.

A specific membrane and nucleus targeted fluorescence OFF-ON-OFF system, using the dodecane/sulfobetaine group of functionalized carbon dots (CD) with a copper ion (Cu2+-CD) based on the presence of pyrophosphate (PPi) molecules and alkaline phosphatase (ALP) activity, for cancer cell detection was designed. The biosensor could be effectively transported from the cytosol to the nucleus in MDAMB cells, but not in MDCK cells due to the response to a change in pH by CD functionalized with zwitterionic groups. The biosensor also showed a membrane-selective regulated route for fusion of long alkyl chain grafted-CD on cell membranes. As a potential sensor, the fluorescence of the prepared Cu2+-CD was significantly quenched due to aggregation. In human cancer MDAMB cells, a nearly complete restoration of the fluorescence intensity of the Cu2+-CD was observed because of the high levels of intracellular PPi, which preferentially bound to Cu2+. After 10 min, in the MDAMB cells, re-quenching of the CD fluorescence occurred because of the high level of intracellular ALP, which can hydrolyze PPi and release the Cu2+ to re-aggregate the CD. In contrast to MDAMB cells, MDCK cells did not show an obvious response to the specific intracellular biomolecules, thus, enabling the biosensor to be used to distinguish between cancer and normal cells. In conclusion, this biosensor has the potential to be a simple and sensitive cancer diagnostic tool that can differentiate normal cells from cancer cells on coated surfaces and in aqueous states.

A tumor microenvironment-responsive wireless strain-pressure hydrogel sensor based on pH-induced controllable nanoparticles was designed for cancer detection in vitro–in vivo model, with excellent ability to distinguish between cancer and normal cells. The pH-responsive nanoparticles (CD-PNB), comprising diol–diol crosslinked semiconducting carbon dots (CDs) and non-conductive polymer (PNB), are sensitive to acidic tumor microenvironments and play crucial role in demonstrating tumor-selective strain-pressure responses. Upon application of strain and pressure, CD-PNB@PVA hydrogel produced distinct electronic signals in the presence of cancer cells (HeLa, PC-3), exhibiting higher strain–pressure sensitivity compared to the normal cells (MDCK, CHO-K1). The strain and pressure gage factors for cancer-cell-treated CD-PNB@PVA hydrogel were found to be 0.7439 and 5.3052 kPa−1, which were higher than normal-cell-treated CD-PNB@PVA hydrogel (0.5009 and 4.2720 kPa−1). CD-PNB@PVA hydrogel demonstrated excellent response in tumor-bearing mice based on in situ and ex situ measurements, with no inflammation during hydrogel implantation. Moreover, wireless sensing system was used along with CD-PNB@PVA hydrogel to simplify monitoring process and obtain real-time conductivity and strain–pressure profiles on smartphone. Thus, this approach constructs a tumor microenvironment-responsive strain–pressure hydrogel sensor and presents potential for sensitive and selective tumor detection in point-of-care diagnostic applications.

This study aims to configure what dimensions make up for smart phone after service quality, and how this service quality affects customer satisfaction...

MoS2 protected LiAl intermetallic compound Li metal anode exhibits a highly reversible Li migration for lithium metal batteries., Rechargeable electrochemical cells with metallic anodes are of increasing scientific and technological interest. The complex composition, poorly defined morphology, heterogeneous chemistry, and unpredictable mechanics of interphases formed spontaneously on the anodes are often examined but rarely controlled. Here, we couple computational studies with experimental analysis of well-defined LiAl electrodes in realistic electrochemical environments to design anodes and interphases of known composition. We compare phase behavior, Li binding energies, and activation energy barriers for adatom transport and study their effects on the electrochemical reversibility of battery cells. As an illustration of potential practical benefits of our findings, we create cells in which LiAl anodes protected by Langmuir-Blodgett MoS2 interphases are paired with 4.1 mAh cm−2 LiNi0.8Co0.1Mn0.1O2 cathodes. These studies reveal that small- and larger-format (196 mAh, 294 Wh kg−1, and 513 Wh liter−1) cells based on protected LiAl anodes exhibit high reversibility and support stable Li migration during recharge of the cells.

Oral mucosal drug delivery systems have been developed to expedite the regeneration of oral mucosa, there are still many challenges related to residence time for drugs because the ceaseless changes of saliva, mouth movement, and involuntary swallowing prevent robust adhesion of drugs and/or drug-loaded biomaterials. Thus, it is highly desirable to develop the delivery platforms exhibiting robust, stable adhesion within oral cavities. Herein, we have developed an adhesive polysaccharide oral patch called ‘Chitoral’ that utilizes chemical principles shown in wet-resistant mussel adhesion. Chitoral plays an important role as an adhesive layer in wet environments. We unexpectedly found that Chitoral instantly dissolves upon contact with saliva and a labial mucous layer, and then the dissolved Chitoral compounds forms an insoluble adhesion layer with mucins at Chitoral/mucous interface nearly immediate actions. Later, Chitoral gradually converts into adhesive hydrogels by the cooperative actions of covalent crosslinking and physical entanglement. The instant, robust muco-adhesion properties of Chitoral provides long-lasting therapeutic effects of drugs resulting enhanced healing of oral ulcer. Thus, mussel-inspired, mucous-resistant adhesive platforms, Chitoral, can be a platform for oral mucosal drug delivery systems.

For practical applications of human embryonic stem cells (hESCs) in regenerative medicine, hESCs should be cultured on a large scale, and at the same time their properties have to be maintained in a controllable manner. Here, we report a chemically defined, scalable culture platform involving co-immobilization of heparin–catechol (HepC) and collagen type-1 (Col) for the long-term maintenance (>18 passages) of hESCs in a feeder-free condition. This platform utilizes a wet-adhesive, mussel-inspired heparin–catechol conjugate as a key component. We hypothesized that the heparin’s affinity toward a wide range of proteins, might support undifferentiated in vitro growth of hESC. In fact, on the HepC-coated substrate, most hESC clumps were adhered (∼78% at passage 2 (P2)) and expressed pluripotency markers (Fig. 2). Although HepC alone wasn’t able to support long-term maintenance of hESCs in a feeder-free system due to decrease in the adhesion rate of hESCs on HepC coating (∼ 44% at P4) during the repeated passaging processes, we found that when collagen type I was co-immobilized in the process of HepC coating, the long-term maintenance (passage 18 or more) of hESCs could be achieved with 100% adhesion efficiency (Fig. 4). One remarkable observation is that hESCs on collagen type-I underwent spontaneous differentiation after P6 (Fig. 3), which implied co-immobilized HepC played a role to suppress differentiation of hESCs. This study suggests that unlike the previous studies using proteins, peptides, or synthetic polymers, a polysaccharide, heparin, can be used as a cost-effective component for chemically defined, feeder-free culture of hESC. Statement of Significance Towards practical applications of human embryonic stem cells (hESCs) in regenerative medicine, hESCs should be cultured on a large scale, and their pluripotent property has to be maintained in a controllable manner. To address these issues, studies that develop chemically defined culture substrates have been explored to replace the widely used, complex, and undefined culture materials represented by Matrigel. Most reports have focused on utilizing proteins, peptides and/or synthetic polymers. However, there have not yet been studies on using polysaccharides as two-dimensional coating materials to potentially replace Matrigel coating. Here, we report that heparin is an effective polysaccharide for the feeder-free, two dimensional culture of hESCs. Our study implies that use of polysaccharides or a polysaccharide/ECM combination can be a new, alternative design principle for hESC culture systems.

Recently, catechol-containing polymers have been extensively developed as promising materials for surgical tissue adhesives, wound dressing, drug delivery depots, and tissue engineering scaffolds. Catechol conjugation to the polymer backbone provides adhesive properties to the tissue and does not significantly affect the intrinsic properties of the polymers. An example of a catecholic polymer is catechol-conjugated hyaluronic acid. In general, hyaluronic acid shows excellent biocompatibility and biodegradability; thus, it is used in various medical applications. However, hyaluronic acid alone has poor mechanical and tissue adhesion properties. Catechol modification considerably increases the mechanical and underwater adhesive properties of hyaluronic acid, while maintaining its biocompatibility and biodegradability and enabling its use in several biomedical applications. In this review, we briefly describe the synthesis and characteristics of catechol-modified hyaluronic acid, with a specific focus on catechol-involving reactions. Finally, we discuss the basic concepts and therapeutic effects of catechol-conjugated hyaluronic acid for biomedical applications.

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal b-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7&minus, /&minus, ) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7&minus, and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7&minus, colons. Upregulated levels of &beta, catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7&minus, mice and downstream targets of &beta, catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7&minus, mice. We observed an increased level of palmitic acid in the colon of Nudt7&minus, mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of b-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in KrasG12D-driven CRC development.

For the increasing demand of soft materials with wide ranges of applications, hydrogels have been developed exhibiting variety of functions (e.g., stretchable, self-healing, stimuli-responsive, and etc.). So far, add-in components such as inorganic nanoparticles, carbon materials, clays, and many others to main polymers have been used to achieve various unique functions of hydrogels. The multicomponent hydrogel systems often exhibit batch-dependent inconsistent results and problems in multicomponent mixings, require labors during preparations, and accompany unpredictable cross-talk between the added components. Here, we developed 'single polymeric component', alginate-boronic acid (alginate-BA) hydrogel to overcome the aforementioned problems. It exhibits unprecedented multifunctionalities simultaneously, such as high stretchability, self-healing, shear-thinning, pH- and glucose-sensitivities, adhesive properties, and reshaping properties. Multifunctionalities of alginate-BA hydrogel is resulted from the reversible inter- and intramolecular interactions by dynamic equilibrium of boronic acid-diol complexation and dissociation, which was proved by single molecule level Atomic Force Microscopy (AFM) pulling experiments. We also found that the alginate-BA gel showed enhanced in vivo retentions along gastrointestinal (GI) tract. Our findings suggest that rational polymer designs can result in minimizing the number of a participating component for multifunctional hydrogels, instead of increasing complexity by adding various additional components.

Background:Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensing platforms. The unique aspect of PBA-polymers is their interactions with diols, which result in reversible, covalent bond formation. This very nature of reversible bonding between boronic acids and diols has been fundamental to their applications in the biomedical area.Methods:We have searched peer-reviewed articles including reviews from Scopus, PubMed, and Google Scholar with a focus on the 1) chemistry of PBA, 2) synthesis of PBA-polymers, and 3) their biomedical applications.Results:We have summarized approximately 179 papers in this review. Most of the applications described in this review are focused on the unique ability of PBA molecules to interact with diol molecules and the dynamic nature of the resulting boronate esters. The strong sensitivity of boronate ester groups towards the surrounding pH also makes these molecules stimuli-responsive. In addition, we also discuss how the re-arrangement of the dynamic boronate ester bonds renders PBA-based materials with other unique features such as self-healing and shear thinning.Conclusion:The presence of PBA in the polymer chain can render it with diverse functions/ relativities without changing their intrinsic properties. In this review, we discuss the development of PBA polymers with diverse functions and their biomedical applications with a specific focus on the dynamic nature of boronate ester groups.

The development of adhesive materials, such as cyanoacrylate derivatives, fibrin glues, and gelatin-based adhesives, has been an emerging topic in biomaterial science because of the many uses of these materials, including in wound healing patches, tissue sealants, and hemostatic materials. However, most bio-adhesives exhibit poor adhesion to tissue and related surfaces due to the presence of body fluid. For a decade, studies have aimed at addressing this issue by developing wet-resistant adhesives. Mussels demonstrate robust wet-resistant adhesion despite the ceaseless waves at seashores, and mussel adhesive proteins play a key role in this adhesion. Adhesive proteins located at the distal end (i.e., those that directly contact surfaces) are composed of nearly 60% of amino acids called 3,4-dihydroxy-l-phenylalanine (DOPA), lysine, and histidine, which contain side chains of catechol, primary amines, and secondary amines, respectively. Inspired by the abundant catecholamine in mussel adhesive proteins, researchers have developed various types of polymeric mimics, such as polyethylenimine-catechol, chitosan-catechol, and other related catecholic polymers. Among them, chitosan-catechol is a promising adhesive polymer for biomedical applications. The conjugation of catechol onto chitosan dramatically increases its solubility from zero to nearly 60mg/mL (i.e., 6% w/v) in pH 7 aqueous solutions. The enhanced solubility maximizes the ability of catecholamine to behave similar to mussel adhesive proteins. Chitosan-catechol is biocompatible and exhibits excellent hemostatic ability and tissue adhesion, and thus, chitosan-catechol will be widely used in a variety of medical settings in the future. This review focuses on the various aspects of chitosan-catechol, including its (1) preparation methods, (2) physicochemical properties, and (3) current applications.

Numerous mucoadhesive polymers have been exploited for prolonging the residence time of formulated drugs or pharmaceuticals at specific delivery sites. However, it has been difficult to achieve satisfactory mucoadhesive properties. The two major modification strategies such as thiolation or lectin functionalization have been extensively studied, but disulfide bond reversibility in the case of thiolation and the toxicity of lectins have been problems. Thus, approaches for further improvement of mucoadhesive properties need to be developed. With an overwhelming library of mucoadhesive polymers, one practical way to improve mucoadhesion is chemical modification of existing mucoadhesive polymers. In other words, the method is based on utilizing the cooperative effect that might be achieved by chemical tethering of a small adhesive moiety to an available mucoadhesive polymer. Here, we conjugated catechols derived from mussel adhesive proteins to chitosan, which is a widely known mucoadhesive polymer. We demonstrated that the gastrointestinal (GI) tract retention of chitosan-catechol was improved compared to unmodified chitosan, which is due to the formation of irreversible catechol mediated-crosslinking with mucin. The results indicate that catechol modification of mucoadhesive polymers may possibly lead to a new generation of mucoadhesive polymers for mucosal drug delivery.

Current hyaluronic acid (HA) hydrogel systems often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective localization of transplanted cells in vivo. In addition, the injection of hydrogel into certain organs (e.g., liver, heart) induces tissue damage and hemorrhage. In this study, we describe a bioinspired, tissue-adhesive hydrogel that overcomes the limitations of current HA hydrogels through its improved biocompatibility and potential for minimally invasive cell transplantation. HA functionalized with an adhesive catecholamine motif of mussel foot protein forms HA-catechol (HA-CA) hydrogel via oxidative crosslinking. HA-CA hydrogel increases viability, reduces apoptosis, and enhances the function of two types of cells (human adipose-derived stem cells and hepatocytes) compared with a typical HA hydrogel crosslinked by photopolymerization. Due to the strong tissue adhesiveness of the HA-CA hydrogel, cells are easily and efficiently transplanted onto various tissues (e.g., liver and heart) without the need for injection. Stem cell therapy using the HA-CA hydrogel increases angiogenesis in vivo, leading to improved treatment of ischemic diseases. HA-CA hydrogel also improved hepatic functions of transplanted hepatocytes in vivo. Thus, this bioinspired, tissue-adhesive HA hydrogel can enhance the efficacy of minimally invasive cell therapy.

Adhesives play an important role in industrial fields such as electronics, architectures, energy plantation, and others. However, adhesives used for medical purpose are rather under-developed compared with those used in industry and consumer products. One key property required for medical adhesives is to maintain their adhesiveness in the presence of body fluid. Here, an entirely new class of medical adhesives called TAPE is reported; this is produced by intermolecular hydrogen bonding between a well-known polyphenol compound, tannic acid, and poly(ethylene glycol). The preparation method of TAPE is extremely easy, forming a few liters at once by just the simple mixing of the two compounds without any further chemical synthetic procedures. TAPE shows a 250% increase in adhesion strength compared with fibrin glue, and the adhesion is well maintained in aqueous environments. It is demonstrated that TAPE is an effective hemostatic material and a biodegradable patch for detecting gastroesophageal reflux disease in vivo. Widespread use of TAPE is anticipated in various medical and pharmaceutical applications such as muco-adhesives, drug depots, and others, because of its scalability, adhesion, and facile preparation.