Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis.

BACKGROUND: Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear. OBJECTIVES: This study aimed to investigate the influence of NETs on the CRS epithelium. METHODS: Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model. RESULTS: NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation. CONCLUSIONS: These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.

Fe-containing metal-organic framework with D-penicillamine for cancer-specific hydrogen peroxide generation and enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) is based on the production of cytotoxic reactive oxygen species, such as hydroxyl radicals (•OH). Thus, CDT can be advantageous when it is cancer-specific, in terms of efficacy and safety. Therefore, we propose NH2-MIL-101(Fe), a Fe-containing metal-organic framework (MOF), as a carrier of Cu (copper)-chelating agent, d-penicillamine (d-pen; i.e., the NH2-MIL-101(Fe)/d-pen), as well as a catalyst with Fe-metal clusters for Fenton reaction. NH2-MIL-101(Fe)/d-pen in the form of nanoparticles was efficiently taken into cancer cells and released d-pen in a sustained manner. The released d-pen chelated Cu that is highly expressed in cancer environments and this produces extra H2O2, which is then decomposed by Fe in NH2-MIL-101(Fe) to generate •OH. Therefore, the cytotoxicity of NH2-MIL-101(Fe)/d-pen was observed in cancer cells, not in normal cells. We also suggest a formulation of NH2-MIL-101(Fe)/d-pen combined with NH2-MIL-101(Fe) loaded with the chemotherapeutic drug, irinotecan (CPT-11; NH2-MIL-101(Fe)/CPT-11). When intratumorally injected into tumor-bearing mice in vivo, this combined formulation exhibited the most prominent anticancer effects among all tested formulations, owing to the synergistic effect of CDT and chemotherapy.

Metal-organic framework for biomimetic nitric oxide generation and anticancer drug delivery.

The potential therapeutic implications of nitric oxide (NO) have drawn a great deal of interest for reversing multidrug resistance (MDR) in cancer; however, previous strategies utilized unstable or toxic NO donors often oxidized by the excessive addition of reactive oxygen species, leading to unexpected side effects. Therefore, this study proposed a metal-organic framework (MOF), Porous coordination network (PCN)-223-Fe, to be loaded with a biocompatible NO donor, L-arginine (L-arg; i.e., PCN-223-Fe/L-arg). This specific MOF possesses a ligand of Fe-porphyrin, a biomimetic catalyst. Thus, with PCN-223-Fe/L-arg, L-arg was released in a sustained manner, which generated NO by a catalytic reaction between L-arg and Fe-porphyrin in PCN-223-Fe. Through this biomimetic process, PCN-223-Fe/L-arg could generate sufficient NO to reverse MDR at the expense of hydrogen peroxide already present and highly expressed in cancer environments. For treatment of MDR cancer, this study also proposed PCN-223-Fe loaded with an anticancer drug, irinotecan (CPT-11; i.e., PCN-223-Fe/CPT-11), to be formulated together with PCN-223-Fe/L-arg. Owing to the synergistic effect of reversed MDR by NO generation and sustained release of CPT-11, this combined formulation exhibited a higher anticancer effect on MDR cancer cells (MCF-7/ADR). When intratumorally injected in vivo, coadministration of PCN-223-Fe/L-arg and PCN-223-Fe/CPT-11 greatly suppressed tumor growth in nude mice bearing MDR tumors.

Evaluation of Paste-Type Micronized Acellular Dermal Matrix for Soft Tissue Augmentation: Volumetric and Histological Assessment in a Mouse Model.

BACKGROUND: A biological injectable material, paste-type micronized acellular dermal matrix (ADM), has been proven effective in wound healing by filling defects through tissue replacement. This study aimed to compare the efficacy of paste-type micronized ADM on soft tissue augmentation with that of the conventional fillers in animal experiments. METHODS: Two distinct paste-type micronized ADMs, which were mixed with distilled water (mADM) and gelatin (mADM+GEL), respectively, were compared with conventional fillers, hyaluronic acid (HA) and polymethyl methacrylate (COL+PMMA). Thus, four different types of fillers were each injected into the dorsum of nude mice to compare the volume retention and biocompatibility. During the 8-week experimental period, ultrasound and computed tomography (CT) images were obtained for volumetric analysis. Histological evaluation was performed using hematoxylin and eosin and CD 31 staining. RESULTS: According to the CT images at week 8, the mADM and mADM+GEL showed a higher volume persistence rate of 113.54% and 51.12%, compared with 85.09% and 17.65% for HA and COL+PMMA, respectively. The 2-week interval ultrasound images revealed that the mADM showed a volume increase in width rather than in height, and an increase in height for HA did not vary much. Histological analysis showed marked fibrous invasion and neovascularization with the mADM and mADM+GEL compared to that of the conventional fillers. CONCLUSIONS: Paste-type micronized ADM showed soft tissue augmentation with similar effectiveness to that of conventional fillers. Therefore, paste-type micronized ADM has potential as an alternative material for a soft tissue filler in tissue replacement. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma.

Patients with high-risk non-metastatic renal cell carcinoma (RCC) are at risk of metastatic relapse following nephrectomy. Cabozantinib (CZ), a potent multitarget tyrosine kinase inhibitor, interferes with angiogenesis and immunosuppression associated with surgery-induced metastasis. Here, we explored the therapeutic potential of CZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CZ-PLGA-NPs) as an adjuvant strategy for targeting post-nephrectomy metastasis. A clinically relevant subline recapitulating post-nephrectomy lung metastasis of high-risk human RCC, namely Renca-SRLu5-Luc, was established through in vivo serial selection of luciferase-expressing murine RCC Renca-Luc cells. CZ was encapsulated into PLGA-NPs via the conventional single emulsion technique. The multifaceted preclinical antimetastatic efficacy of CZ-PLGA-NPs was assessed in Renca-SRLu5-Luc cells. CZ-PLGA-NPs with a smooth surface displayed desirable physicochemical properties, good CZ encapsulation efficiency, as well as controlled and sustained CZ release. CZ-PLGA-NPs exhibited remarkable dose-dependent toxicity against Renca-SRLu5-Luc cells by inducing G2/M cell cycle arrest and apoptosis. CZ-PLGA-NPs attenuated in vitro colony formation, migration, and invasion by abrogating AKT and ERK1/2 activation. An intravenous injection of CZ-PLGA-NPs markedly reduced lung metastatic burden and prolonged lifespan with favorable safety in the Renca-SRLu5-Luc experimental lung metastasis model. The novel CZ-PLGA-NPs system with multifaceted antimetastatic effects and alleviating off-target toxicity potential is a promising adjunctive agent for patients with surgically resected high-risk RCC.

Image-guided in situ cancer vaccination with combination of multi-functional nano-adjuvant and an irreversible electroporation technique.

Cancer immunotherapy is a next-generation treatment strategy; however, its side effects limit its clinical translation. Here, a novel combination of a multi-functional nano-adjuvant (M-NA) prepared with an iron oxide/gold core and a cationic polymer shell via multilayer synthesis with CpG oligodeoxynucleotide (CpG-ODN) electrostatically complexed on its surface, and irreversible electroporation (IRE) technique was developed for effective image-guided in situ cancer vaccination. The M-NA can be retained long-term in the dense tumoral extracellular matrix after intratumoral injection and internalized by antigen-presenting cells (APCs). The IRE can induce immunogenic cell death. Indeed, in a mouse tumor model, the M-NA showed longer tumor retention time than free CpG-ODN. Compared with other treatments, the combined treatment significantly inhibited tumor growth with 100% survival rate for ∼60 days. The therapy induced the activation of cytotoxic lymphocytes and the maturation of APCs in vivo. This treatment could be effective in image-guided local cancer immunotherapy.

Micro-textured silicone-based implant fabrication using electrospun fibers as a sacrificial template to suppress fibrous capsule formation.

Conventionally, macro-textured surfaces comprising several hundred micrometer-sized patterns are used to minimize silicone-based breast implant complications, including capsular contracture. However, because of the recent cases of breast implant-associated anaplastic large cell lymphoma from macro-textured implants, there is a strong demand for nano- or micro-textured silicone implants with dimensions smaller than sub-micrometers. Herein, we propose a simple and cost-effective topographical surface modification strategy for silicone-based implants. Several hundred nanometer to sub-micrometer wide groove-type micro-textures were fabricated on a polydimethylsiloxane surface using electrospun polyvinylpyrrolidone fibers as a sacrificial template. The aligned and randomly oriented micro-textures were prepared by controlling the electrospun fiber orientation. In vitro experiments demonstrated that the micro-textured polydimethylsiloxane was cytocompatible and suppressed differentiation of fibroblasts into myofibroblasts. Importantly, the aligned micro-texture promoted the polarization of macrophages into the anti-inflammatory M2 phenotype. Long-term in vivo studies established that the micro-textures potently suppressed various factors affecting foreign body reactions by downregulating profibrotic cytokine gene expression and reducing the fibroblast and myofibroblast counts, the cells playing important roles in the immune response. Thus, the thickness and collagen density of fibrous capsules were decreased, demonstrating that the micro-textured surface effectively inhibited capsular contracture. Although the aligned micro-textures contributed to the polarization of macrophages to the M2 phenotype both in vitro and in vivo, foreign body reaction by both the aligned and randomly oriented micro-textures are similar.

Silicone Breast Implant Coated with Triamcinolone Inhibited Breast-Implant-Induced Fibrosis in a Porcine Model.

Cosmetic silicone implants for breast reconstruction often lead to medical complications, such as abnormally excessive fibrosis driven by foreign body granulomatous inflammation. The purpose of this study was to develop a silicone breast implant capable of local and controlled release of a glucocorticoid drug triamcinolone acetonide (TA) for the prevention of silicone-breast-implant-induced fibrosis in a Yorkshire pig model (in vivo). Implants were dip-coated in a TA solution to load 1.85 µg/cm2 of TA in the implant shell, which could release the drug in a sustained manner for over 50 days. Immunohistochemical analysis for 12 weeks showed a decline in tumor necrosis factor-α expression, capsule thickness, and collagen density by 82.2%, 55.2%, and 32.3%, respectively. Furthermore, the counts of fibroblasts, macrophages, and myofibroblasts in the TA-coated implants were drastically reduced by 57.78%, 48.8%, and 64.02%, respectively. The TA-coated implants also lowered the expression of vimentin and α-smooth muscle actin proteins, the major profibrotic fibroblast and myofibroblast markers, respectively. Our findings suggest that TA-coated silicone breast implants can be a promising strategy for safely preventing fibrosis around the implants.

Indwelling urinary catheter assembled with lidocaine-loaded polymeric strand for local sustained alleviation of bladder discomfort.

Indwelling urinary catheters (IUCs) are used in clinical settings to assist detrusor contraction in hospitalized patients. However, an inserted IUC often causes catheter-related bladder discomfort. To resolve this, we propose an IUC coupled with local, sustained release of an anesthetic drug, lidocaine. For this, a thin strand composed of poly (lactic-co-glycolic acid) and lidocaine was separately prepared as a drug delivery carrier, which was then wound around the surface of the IUC to produce the drug-delivery IUC. Our results revealed that the drug-delivery IUC could exert the pain-relief effects for up to 7 days when placed in the bladder of living rats. Cystometrogram tests indicated that the drug-delivery IUC could significantly relieve bladder discomfort compared with the IUC without lidocaine. Furthermore, the expression of pain-related inflammatory markers, such as nerve growth factor, cyclooxygenase-2, and interleukin-6 in the biopsied bladder tissues was significantly lower when the drug-delivery IUC was used. Therefore, we conclude that an IUC simply assembled with a drug-loaded polymer strand can continuously release lidocaine to allow for the relief of bladder discomfort during the period of IUC insertion.

Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson's disease rat model.

Parkinson's disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. Coenzyme Q10, an antioxidant, has been considered a promising neuroprotective agent; however, conventional oral administration provides limited efficacy due to its very low bioavailability. In this study, we hypothesised that continuous, intrastriatal administration of a low dose of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson's disease rat model induced by 6-hydroxydopamine was established, and the treatment was applied a week before the full establishment of this disease model. Behavioural tests showed a dramatically decreased number of asymmetric rotations in the intrastriatal Coenzyme Q10 group compared with the no treatment group. Rats with intrastriatal Coenzyme Q10 exposure also exhibited a larger number of dopaminergic neurons, higher expression of neurogenetic and angiogenetic factors, and less inflammation, and the effects were more prominent than those of orally administered Coenzyme Q10, although the dose of intrastriatal Coenzyme Q10 was 17,000-times lower than that of orally-administered Coenzyme Q10. Therefore, continuous, intrastriatal delivery of Coenzyme Q10, especially when combined with implantable devices for convection-enhanced delivery or deep brain stimulation, can be an effective strategy to prevent neurodegeneration in Parkinson's disease.

Designing Minimally Invasive Preocular Contact Tips for Potential Application in Tear Collection.

PURPOSE: Basal tear fluid has drawn great attention as a medium for many disease markers and, hence, for its potential to be used in self-diagnosis. However, collection of basal tear fluid is difficult because a conventional tear collector, such as a glass capillary tube, may inflict irritation or damage on the sensitive ocular surface. Therefore, we sought to design a tip for contact with the preocular surface [a preocular contact tip (PCT)] that minimizes damage to the ocular surface. METHODS: We designed the shape of the tip to have rounded boundaries and no sharp edges. We then tested different tip areas, each of which was contacted with the inferior palpebral conjunctiva of rabbit eyes at varying depths to demonstrate their feasibility in vivo. The area of damaged tissue and the time required for tissue recovery were monitored according to the pressure applied through the tips. RESULTS: Our findings revealed that a contact area of the PCT greater than 2.36 mm caused relatively little damage to the inferior palpebral conjunctival tissue, which could recover within 4 hours after contact at all pressing depths. In contrast, a glass capillary tube caused relatively severe damage, which did not recover for more than 8 hours. The PCT (3.14 mm) was embedded with a microchannel as a prototype tear collector, which could collect 0.3 µL of tears with minimal tissue damage. CONCLUSIONS: The PCT proposed in this study can be a promising tool for minimally invasive collection of basal tears from the inferior palpebral conjunctiva.

Development of Poly(HEMA-Am) Polymer Hydrogel Filler for Soft Tissue Reconstruction by Facile Polymerization.

The number of breast reconstruction surgeries has been increasing due to the increase in mastectomies. Surgical implants (the standard polydimethylsiloxane (PDMS) implants) are widely used to reconstruct breast tissues, however, it can cause problems such as adverse immune reactions, fibrosis, rupture, and additional surgery. Hence, polymeric fillers have recently garnered increasing attention as strong alternatives for breast reconstruction materials. Polymeric fillers offer noninvasive methods of reconstruction, thereby reducing the possible adverse effects and simplifying the treatment. In this study, we synthesized a 2-hydroxylethylmethacrylate (HEMA) and acrylamide (Am) copolymer (Poly(HEMA-Am)) by redox polymerization to be used as a biocompatible filler material for breast reconstruction. The synthesized hydrogel swelled in phosphate buffered saline (PBS) shows an average modulus of 50 Pa, which is a characteristic similar to that of the standard dermal acrylamide filler. To investigate the biocompatibility and cytotoxicity of the Poly(HEMA-Am) hydrogel, we evaluated an in vitro cytotoxicity assay on human fibroblasts (hFBs) and human adipose-derived stem cells (hADSCs) with the hydrogel eluate, and confirmed a cell viability of over 80% of the cell viability with the Poly(HEMA-Am) hydrogel. These results suggest our polymeric hydrogel is a promising filler material in soft tissue augmentation including breast reconstruction.

Surgical suture releasing macrophage-targeted drug-loaded nanoparticles for an enhanced anti-inflammatory effect.

A surgical suture is a medical device to close the wound site of skin and organs but excessive inflammation surrounding the suture can disrupt the wound healing process. Although post-operative prescription of anti-inflammatory drugs is used to manage the inflammation, the need for local drug delivery systems has been rising because of low bioavailability and fast clearance of drugs. In this work, we proposed a new strategy for a local anti-inflammatory device by incorporating macrophage-targeted anti-inflammatory nanoparticles into the suture. For macrophage-targeted anti-inflammatory nanoparticles, poly(lactic-co-glycolic) nanoparticles were loaded with anti-inflammatory drug diclofenac and decorated with polyethylene glycol and macrophage-targeting ligand mannose. These anti-inflammatory nanoparticles released diclofenac sustainably, and targeted activated macrophages efficiently. After nanoparticle optimization, a suture was coated with multiple layers of macrophage-targeted anti-inflammatory nanoparticles using a dip coating process. The suture releasing macrophage-targeted anti-inflammatory nanoparticles showed an enhanced anti-inflammatory effect in both macrophage culture and excisional wound healing animal models compared to a free drug molecule-coated suture. These results suggest that anti-inflammatory nanoparticle-coated sutures have great potential as an effective local delivery system to reduce inflammation and pain at the wound site.

Implantable batteryless device for on-demand and pulsatile insulin administration.

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.

Prolonged, acute suppression of cysteinyl leukotriene to reduce capsular contracture around silicone implants.

We hypothesize that periodically early, local suppression of cysteinyl leukotrienes (CysLTs), which are potent inflammatory mediators, can reduce the fibrotic capsular contracture around silicone implants. We tested this hypothesis with the silicone implants enabled with the sustained release of montelukast, a CysLT receptor antagonist, for 3 and 15days. In this work, we inserted each of the distinct implants into the pocket of the subpanniculus carnosus plane of living rats and performed histological and immunofluorescent (IF) analyses of the tissues biopsied at predetermined periods for 12weeks after implant insertion. The implants with montelukast exhibited significantly reduced polymorphonuclear leukocytes (i.e., PMNs), implying a concurrent reduction of CysLT. This effect was more prominent after long-term local montelukast exposure. Thus, fewer fibroblasts were recruited, thereby reducing transforming growth factor (TGF)-ß and myofibroblasts in the tissue around the implant. Therefore, the fibrotic capsule formation, which was assessed using the capsule thickness and collagen density, decreased along with the myofibroblasts. Additionally, the tissue biopsied at the experimental end point exhibited significantly decreased mechanical stiffness. STATEMENT OF SIGNIFICANCE: Capsular contracture is troublesome, making the tissues hardened around the silicone implant. This causes serious pain and discomfort to the patients, often leading to secondary surgery for implant replacement. To resolve this, we suggest a strategy of long-term, local suppression of cysteinyl leukotriene, an important mediator present during inflammation. For this, we propose a silicone implant abled to release a drug, montelukast, in a sustained manner. We tested our drug-release implant in living animals, which exhibited a significant decrease in capsule formation compared with the intact silicone implant. Therefore, we conclude that the sustained release of montelukast at the local insertion site represents a promising way to reduce capsular contracture around silicone implants.

Sinonasal Delivery of Resveratrol via Mucoadhesive Nanostructured Microparticles in a Nasal Polyp Mouse Model.

Resveratrol (RSV) has been shown to effectively suppress chronic rhinosinusitis with nasal polyps in a mouse model; however, when locally administered to the sinonasal cavity, bolus RSV is limited by low drug bioavailability owing to its low aqueous solubility and relatively rapid clearance from the administration site. To address this limitation, we propose mucoadhesive nanostructured microparticles (PLGA/PEG NM) as a potential carrier for the sinonasal delivery of RSV. In this study, PLGA/PEG NM released RSV in a sustained manner. Owing to the enlarged specific surface area of the nanostructures, PLGA/PEG NM had synergistically enhanced mucoadhesiveness and thus showed improved in vivo retention properties in the sinonasal cavity. Therefore, when tested in a mouse nasal polyp model, PLGA/PEG NM mitigated polyp formation and restored epithelial integrity better than the control treatments. The therapeutic effect was similar at half the dose of PLGA/PEG NM, suggesting improved local bioavailability of RSV in the sinonasal cavity.

Bioabsorbable bone plates enabled with local, sustained delivery of alendronate for bone regeneration.

We prepared a bone plate enabled with the local, sustained release of alendronate, which is a drug known to inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts. For this, we coated a bone plate already in clinical use (PLT-1031, Inion, Finland) with a blend of alendronate and a biocompatible polymer, azidobenzoic acid-modified chitosan (i.e., Az-CH) photo-crosslinked by UV irradiation. As we performed the in vitro drug release study, the drug was released from the coating at an average rate of 4.03µg/day for 63days in a sustained manner. To examine the effect on bone regeneration, the plate was fixed on an 8mm cranial critical size defect in living rats and the newly formed bone volume was quantitatively evaluated by micro-computed tomography (micro-CT) at scheduled times over 8weeks. At week 8, the group implanted with the plate enabled with sustained delivery of alendronate showed a significantly higher volume of newly formed bone (52.78±6.84%) than the groups implanted with the plates without drug (23.6±3.81%) (p<0.05). The plate enabled with alendronate delivery also exhibited good biocompatibility on H&E staining, which was comparable to the Inion plate already in clinical use. Therefore, we suggest that a bone plate enabled with local, sustained delivery of alendronate can be a promising system with the combined functionality of bone fixation and its expedited repair.

Surface coating for prevention of metallic seed migration in tissues.

PURPOSE: In radiotherapy, metallic implants often detach from their deposited sites and migrate to other locations. This undesirable migration could cause inadequate dose coverage for permanent brachytherapy and difficulties in image-guided radiation delivery for patients. To prevent migration of implanted seeds, the authors propose a potential strategy to use a biocompatible and tissue-adhesive material called polydopamine. METHODS: In this study, nonradioactive dummy seeds that have the same geometry and composition as commercial I-125 seeds were coated in polydopamine. Using scanning electron microscopy and x-ray photoelectron spectroscopy, the surface of the polydopamine-coated and noncoated seeds was characterized. The detachment stress between the two types of seeds and the tissue was measured. The efficacy of polydopamine-coated seed was investigated through in vitro migration tests by tracing the seed location after tissue implantation and shaking for given times. The cytotoxicity of the polydopamine coating was also evaluated. RESULTS: The results of the coating characterization have shown that polydopamine was successfully coated on the surface of the seeds. In the adhesion test, the polydopamine-coated seeds had 2.1-fold greater detachment stress than noncoated seeds. From the in vitro test, it was determined that the polydopamine-coated seed migrated shorter distances than the noncoated seed. This difference was increased with a greater length of time after implantation. CONCLUSIONS: The authors suggest that polydopamine coating is an effective technique to prevent migration of implanted seeds, especially for permanent prostate brachytherapy.

Acute suppression of TGF-ß with local, sustained release of tranilast against the formation of fibrous capsules around silicone implants.

We propose the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation.

Bioabsorbable bone fixation plates for X-ray imaging diagnosis by a radiopaque layer of barium sulfate and poly(lactic-co-glycolic acid).

Bone fixation systems made of biodegradable polymers are radiolucent, making post-operative diagnosis with X-ray imaging a challenge. In this study, to allow X-ray visibility, we separately prepared a radiopaque layer and attached it to a bioabsorbable bone plate approved for clinical use (Inion, Finland). We employed barium sulfate as a radiopaque material due to the high X-ray attenuation coefficient of barium (2.196 cm(2) /g). The radiopaque layer was composed of a fine powder of barium sulfate bound to a biodegradable material, poly(lactic-co-glycolic acid) (PLGA), to allow layer degradation similar to the original Inion bone plate. In this study, we varied the mass ratio of barium sulfate and PLGA in the layer between 3:1 w/w and 10:1 w/w to modulate the degree and longevity of X-ray visibility. All radiopaque plates herein were visible via X-ray, both in vitro and in vivo, for up to 40 days. For all layer types, the radio-opacity decreased with time due to the swelling and degradation of PLGA, and the change in the layer shape was more apparent for layers with a higher PLGA content. The radiopaque plates released, at most, 0.5 mg of barium sulfate every 2 days in a simulated in vitro environment, which did not appear to affect the cytotoxicity. The radiopaque plates also exhibited good biocompatibility, similar to that of the Inion plate. Therefore, we concluded that the barium sulfate-based, biodegradable plate prepared in this work has the potential to be used as a fixation device with both X-ray visibility and biocompatibility.