Effect of Tannic Acid Concentrations on Temperature-Sensitive Sol-Gel Transition and Stability of Tannic Acid/Pluronic F127 Composite Hydrogels.

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Hydrophilic/Hydrophobic Janus Nanofibers Containing Compound K for Cartilage Regeneration.

Introduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects. Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1ß (IL-1ß) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated. Results: CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1ß was reduced through the upregulation of PPAR. Conclusion: CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1ß via increasing PPAR.

Coagulant Protein-Free Blood Coagulation Using Catechol-Conjugated Adhesive Chitosan/Gelatin Double Layer.

Since the discovery of polyphenolic underwater adhesion in marine mussels, researchers strive to emulate this natural phenomenon in the development of adhesive hemostatic materials. In this study, bio-inspired hemostatic materials that lead to pseudo-active blood coagulation, utilizing traditionally passive polymer matrices of chitosan and gelatin are developed. The two-layer configuration, consisting of a thin, blood-clotting catechol-conjugated chitosan (CHI-C) layer and a thick, barrier-functioning gelatin (Geln) ad-layer, maximizes hemostatic capability and usability. The unique combination of coagulant protein-free condition with CHI-C showcases not only coagulopathy-independent blood clotting properties (efficacy) but also exceptional clinical potential, meeting all necessary biocompatibility evaluation (safety) without inclusion of conventional coagulation triggering proteins such as thrombin or fibrinogen. As a result, the CHI-C/Geln is approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) as a class II medical device. Hemostatic efficacy observed in multiple animal models further demonstrates the superiority of CHI-C/Geln sponges in achieving quick hemostasis compared to standard treatments. This study not only enriches the growing body of research on mussel-inspired materials but also emphasizes the potential of biomimicry in developing advanced medical materials, contributing a promising avenue toward development of readily accessible and affordable hemostatic materials.

Bio-Inspired Self-Healing, Shear-Thinning, and Adhesive Gallic Acid-Conjugated Chitosan/Carbon Black Composite Hydrogels as Suture Support Materials.

The occurrence of leakage from anastomotic sites is a significant issue given its potential undesirable complications. The management of anastomotic leakage after gastrointestinal surgery is particularly crucial because it is directly associated with mortality and morbidity in patients. If adhesive materials could be used to support suturing in surgical procedures, many complications caused by leakage from the anastomosis sites could be prevented. In this study, we have developed self-healing, shear-thinning, tissue-adhesive, carbon-black-containing, gallic acid-conjugated chitosan (CB/Chi-gallol) hydrogels as sealing materials to be used with suturing. The addition of CB into Chi-gallol solution resulted in the formation of a crosslinked hydrogel with instantaneous solidification. In addition, these CB/Chi-gallol hydrogels showed enhancement of the elastic modulus (G') values with increased CB concentration. Furthermore, these hydrogels exhibited excellent self-healing, shear-thinning, and tissue-adhesive properties. Notably, the hydrogels successfully sealed the incision site with suturing, resulting in a significant increase in the bursting pressure. The proposed self-healing and adhesive hydrogels are potentially useful in versatile biomedical applications, particularly as suture support materials for surgical procedures.

Double-layer adhesives for preventing anastomotic leakage and reducing post-surgical adhesion.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery.

Carbon black-containing self-healing adhesive hydrogels for endoscopic tattooing.

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.

An all-arthroscopic surgery technique for snapping popliteal tendon syndrome: A case report and literature review.

RATIONALE: 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. PATIENT CONCERNS: 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. DIAGNOSES: Snapping popliteus tendon syndrome. INTERVENTIONS: 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. OUTCOMES: Full range of motion (ROM) was recovered 6 weeks after surgery and the snapping did not recur. LESSONS: 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.

Rapidly progressive gas-forming infection involving the spine as a life-threatening fatal condition : a case report.

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.

Long-Segmental Posterior Fusion Combined With Vertebroplasty and Wiring: Alternative Surgical Technique for Kummell's Disease With Neurologic Deficits-A Retrospective Case Series.

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 segmental kyphotic angle (SKA). 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 SKA 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 SKA) 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.

Cerebrospinal fluid-cutaneous fistula associated with post-traumatic Charcot spinal arthropathy: a case report and review of literature.

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.

Diselenide-Bridged Carbon-Dot-Mediated Self-Healing, Conductive, and Adhesive Wireless Hydrogel Sensors for Label-Free Breast Cancer Detection.

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.

NUDT7 Loss Promotes KrasG12D CRC Development.

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-/-) 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-/- and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7-/- colons. Upregulated levels of ß-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7-/- mice and downstream targets of ß-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7-/- mice. We observed an increased level of palmitic acid in the colon of Nudt7-/- 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.

Polydopamine Surface Chemistry: A Decade of Discovery.

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.

Membrane and nucleus targeting for highly sensitive cancer cell detection using pyrophosphate and alkaline phosphatase activity-mediated fluorescence switching of functionalized carbon dots.

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.

Quadriplegia caused by an epidural abscess occurring at the same level of cervical destructive spondyloarthropathy: a case report.

BACKGROUND: Destructive spondyloarthropathy (DSA) is one of the major complications in patients undergoing long-term hemodialysis. To the best of our knowledge, an epidural abscess occurring at the level of preexisting cervical DSA has not been well described in the literature. We report a unique case of quadriplegia caused by an epidural abscess occurring at the same level of preexisting cervical DSA. CASE PRESENTATION: A 49-year-old woman was transferred to our emergency department with 5 days of sepsis, drowsy mental status, and quadriplegia below the C5 level. The patient had a medical history of hemodialysis for 10 years. Magnetic resonance imaging showed spinal cord compression by an epidural abscess at the level of preexisting cervical DSA. Blood culture revealed methicillin-sensitive Staphylococcus aureus. Infection of the arteriovenous (AV) shunt was considered as the primary focus of sepsis and pyogenic spondylitis. We performed an emergent open door laminoplasty and the vascular team debrided the infected AV shunt site. Approximately 8 months after surgery, the patient was able to perform activities of daily living somewhat independently. CONCLUSIONS: Emergent surgical decompression and intensive medical care led to successful recovery from a septic and quadriplegic state in this patient. When diagnosing a patient who has undergone long-term hemodialysis presenting with neurologic deficits, the possibility of infectious spondylitis at the same level as DSA should be considered.

Comparison of lumbar discectomy alone and lumbar discectomy with direct repair of pars defect for patients with disc herniation and spondylolysis at the nearby lumbar segment.

BACKGROUND CONTEXT: It is unknown whether direct repair (DR) of pars defect after lumbar discectomy (LD) for patients with lumbar disc herniation (LDH) and spondylolysis leads to better outcomes than LD alone. PURPOSE: The aim was to compare two surgical methods, LD alone and LD with DR, for LDH patients with spondylolysis at a nearby lumbar segment. STUDY DESIGN: This was a retrospective comparative study. PATIENT SAMPLE: This study enrolled 89 patients who were diagnosed with LDH and spondylolysis at the same or adjacent lumbar segment and were followed up for at least 1 year. OUTCOME MEASURE: The primary outcome was pain intensity of the lower back and lower extremities as measured with visual analog scale. Secondary outcomes included clinical outcomes as assessed with the Oswestry Disability Index and the 12-item short form health survey, radiologic outcomes as assessed with the gap distance and the union rate at the pars defect, surgical outcomes, and complications. METHODS: Enrolled patients were classified into two groups: LD alone (Group A, 48 patients) and LD with DR (Group B, 41 patients). RESULTS: Pain intensity of the lower back and lower extremities and clinical outcomes were significantly improved 1 year after surgery compared with preoperative scores. However, the scores in the group receiving LD alone steadily worsened during follow-up, whereas the scores in the group receiving LD with DR did not deteriorate over time. The difference in the gap distance of the pars defect between baseline and 1 year after surgery was significantly different between the groups. The fusion rate of the pars defect was 59% (24/41). With the exception of surgical time, which was longer in Group B, surgical outcomes and complications did not differ significantly between the groups. CONCLUSIONS: At the 1-year follow-up, DR after LD was associated with better outcomes for LDH with spondylolysis than LD alone.

Adhesive barrier/directional controlled release for cartilage repair by endogenous progenitor cell recruitment.

A new design concept in controlled release chemistry is reported in this study. Unlike current depots that release drugs in all direction by an isotropic way, we demonstrate that directional release only to a clinically beneficial direction results in improved disease treatment. To achieve the directional drug release, catecholamine adhesion chemistry was used to establish robust interfacial adhesion. For this purpose, water-resistant catechol-conjugated chitosan (CHI-C) adhesive gel patch was used. We chose a cartilage repair model to test our hypothesis. The adhesive barrier exhibited directional release of platelet-derived growth factor-AA (PDGF-AA) only toward the marrow cavity defect areas. This directional PDGF-AA release greatly promoted effective recruitment of human mesenchymal stem cell (hMSCs). Moreover, the adhesive barrier prevented further migration and dispersion of the hMSCs that otherwise were not properly located to the disease site. In vivo imaging and macroscopic histological assessments demonstrated significant improvement of cartilage tissue, suggesting directional controlled release can be a general concept for improvement of tissue regeneration. This CHI-C barrier is expected to make a significant contribution in cartilage tissue engineering without cell transplantation as well as application for other tissue engineering.

Chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes for magnetically modulated cancer hyperthermia.

Magnetic nanoparticles have gained significant attention as a therapeutic agent for cancer treatment. Herein, we developed chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes (Chito-FIONs) as an effective heat nanomediator for cancer hyperthermia. Dynamic light scattering and transmission electron microscopic analyses revealed that Chito-FIONs were composed of multiple 30-nm-sized FIONs encapsulated by a chitosan polymer shell. Multiple FIONs in an interior increased the total magnetic moments, which leads to localized accumulation under an applied magnetic field. Chito-FIONs also exhibited superior magnetic heating ability with a high specific loss power value (2614 W/g) compared with commercial superparamagnetic Feridex nanoparticles (83 W/g). The magnetically guided Chito-FIONs successfully eradicated target cancer cells through caspase-mediated apoptosis. Furthermore, Chito-FIONs showed excellent antitumor efficacy on an animal tumor model without any severe toxicity.