Injectable tissue prosthesis for instantaneous closed-loop rehabilitation.

To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues1,2. Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces3-5. Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage.

Agentes de abultamiento en incontinencia de orina de esfuerzo femenina: una alternativa a las mallas suburetrales / Bulking agents in female stress urinary incontinence: an alternative to suburethral mesh

OBJETIVO: Presentar una serie de casos de agentes de abultamiento (AA) de nuestro centro. MATERIAL Y MÉTODOS: Estudio retrospectivo. Se evaluaron todos los casos operados con AA entre 2017 y 2022. La inyección de AA se realizó en quirófano, bajo sedación con anestesia local periuretral o raquídea. La inyección se realizó con uretroscopia, 0,5 cc en 4 puntos periuretrales (horas 2, 5, 7 y 10). Se analizaron datos demográficos, quirúrgicos y de seguimiento. RESULTADOS: 15 casos. 13/15 presentaron incontinencia urinaria mixta. Solo dos casos tenían incontinencia de orina de esfuerzo pura. El procedimiento fue ambulatorio. La mediana del tiempo operatorio fue 15 minutos (15-20). La mediana de seguimiento fue 5 meses (1-9). El índice de severidad preoperatorio promedio fue 10,6 y en el seguimiento fue 2,79. La Escala de Mejoría Global mostró mejoría en 12/15, y 12/15 estaban satisfechas con la cirugía con mejoría en la calidad de vida. CONCLUSIÓN: Los AA son una opción quirúrgica efectiva, con una tasa de éxito del 80% en otros reportes, siendo similar con nuestra casuística. Ofrecer esta opción es posible a la hora de hablar de terapias alternativas.

OBJECTIVE: To present a case series of bulking agents (BA) from our center. MATERIAL AND METHODS: Retrospective study. All cases operated with BA between 2017 and 2022 were evaluated. A BA injection was performed in the operating room, under periurethral local anesthesia sedation or spinal anesthesia. The injection was performed with urethroscopy, 0.5 cc in 4 periurethral points (hours 2, 5, 7 and 10). Demographic, surgical, and follow-up data were analyzed. RESULTS: 15 cases were reported. 13/15 patients presented with mixed urinary incontinence. Only 2 cases had pure stress urinary incontinence. The procedure was ambulatory. Median operative time was 15 minutes (15-20). Median follow-up was 5 months (1-9). The average preoperative Sandvik Severity Index was 10.6 and in follow-up was 2.79. The PGI showed improvement in 12/15, and 12/15 were satisfied with the surgery with quality-of-life improvement. CONCLUSION: BA are an effective surgical option, with a success rate of 80%, according to other reports, being similar with our casuistry. Offer this option is possible at the moment of discussing alternative therapies.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

BACKGROUND: Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. AIMS: By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. MATERIALS AND METHODS: We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. RESULTS: We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. DISCUSSION: Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. CONCLUSION: Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease.

Emerging evidence indicates that a vicious cycle between inflammation and microthrombosis catalyzes the pathogenesis of inflammatory bowel disease (IBD). Over-stimulated inflammation triggers a coagulation cascade and leads to microthrombosis, which further complicates the injury through tissue hypoxia and ischemia. Herein, an injectable protein hydrogel with anti-thrombosis and anti-inflammation competency is developed to impede this cycle, cross-linked by silver ion mediated metal-ligand coordination and electronic interaction with sulfhydryl functionalized bovine serum albumin and heparin, respectively. The ex vivo experiments show that the hydrogel, HEP-Ag-BSA, exhibits excellent self-healing ability, injectability, biocompatibility, and sustained drug release. HEP-Ag-BSA also demonstrates anti-coagulation and anti-inflammation abilities via coagulation analysis and lipopolysaccharide stimulation assay. The in vivo imaging confirms the longer retention time of HEP-Ag-BSA at inflammatory sites than in normal mucosa owing to electrostatic interactions. The in vivo study applying a mouse model with colitis also reveals that HEP-Ag-BSA can robustly inhibit inflammatory microthrombosis with reduced bleeding risk. This versatile protein hydrogel platform can definitively hinder the "inflammation and microthrombosis" cycle, providing a novel integrated approach against IBD.

Ultrasound-Enhanced Reactive Oxygen Species Responsive Charge-Reversal Polymeric Nanocarriers for Efficient Pancreatic Cancer Gene Delivery.

Inefficient intracellular gene release and transfection limit nonviral gene delivery applications in cancer therapy. Reactive oxygen species (ROS) responsive nonviral gene delivery is the most widely explored strategy for such applications, yet the development of fast and safe ROS responsive nanocarriers proves to be a challenge because of the intracellular chemical equilibrium of high ROS and glutathione levels. Here, we report an ultrasound-enhanced ROS responsive charge-reversal polymeric nanocarrier (BTIL) for fast and efficient pancreatic cancer gene delivery. The BTIL is composed of B-PDEAEA/DNA polyplex-based cores and IR780-loaded liposome coatings. The IR780 is able to produce an excess of ROS under low intensity ultrasound irradiation, thus disequilibrating the chemical equilibrium of ROS and glutathione, and promoting the ROS-responsive positive-to-negative charge-reversal of the B-PDEAEA polymer. This charge conversion results in fast polyplex dissociation and intracellular gene release, inducing efficient gene transfection and cancer cell apoptosis. Moreover, following the intravenous administration, BTIL maintains a stable and long circulation in the bloodstream, achieves orthotopic pancreatic ductal adenocarcinoma distribution, and exhibits potent antitumor activity with negligible side effects. Our results reveal the proposed strategy to be both promising and universal for the development of fast and safe ROS responsive nonviral gene delivery in cancer therapy.

Multistage-Responsive Nanocomplexes Attenuate Ulcerative Colitis by Improving the Accumulation and Distribution of Oral Nucleic Acid Drugs in the Colon.

Oral gene therapy has emerged as a potential optimal treatment for ulcerative colitis (UC). Nucleic acid drugs possessing versatility can not only inhibit inflammation but realize colon mucosal healing, fulfilling the clinical objective of UC therapy. However, the effective accumulation and distribution of oral nucleic acid drugs in the colon remain a considerable challenge. Furthermore, current delivery systems pay more attention to the accumulation of nucleic acid drugs in the colon, while the distribution of nucleic acid drugs in the colon, which plays a key role in the UC treatment, never catches the attention of researchers. Here, we used miR-320 as a model nucleic acid drug to develop a kind of multistage-responsive nanocomplexes (MSNs) based on polymeric nanocapsules and alginate. MSNs possess the pH responsiveness in the stomach, the enzyme responsiveness in the colonic lumen, and the redox responsiveness in the cytoplasm. In vivo imaging results showed that MSNs reach the colon within 2 h and effectively release miR-320 nanocapsules in the colonic lumen. The nanocapsules can further deliver miR-320 to the submucosal layer and even the muscular layer. Moreover, MSNs decreased the activity of myeloperoxidase and proinflammatory cytokines and exhibited anti-inflammatory activity by inhibiting the phosphorylation of IκBα and AKT, reducing colonic inflammation and enhancing mucosal repair. Therefore, MSNs can successfully alleviate UC by improving the accumulation and distribution of oral nucleic acid drugs in the colon, promoting the clinical translational application of nucleic acid drugs in the treatment of UC.

Rapidly Self-Deactivating and Injectable Succinyl Ester-Based Bioadhesives for Postoperative Antiadhesion.

Postoperative adhesion not only causes severe complications for patients but also increases their economic burden. Injectable bioadhesives with adhesiveness to tissues can cover irregular wounds and stay stable in situ, which is a promising barrier for antiadhesion. However, the potential tissue adhesion caused by bioadhesives' indiscriminate adhesiveness between normal and wounded tissue is still a problem. Herein, by using poly(ethylene glycol) succinimidyl succinate (PEG-SS) and gelatin, a succinyl ester-based bioadhesive (SEgel) was fabricated with self-deactivating properties for postoperative antiadhesion. Because N-hydroxysuccinimide esters (NHS-esters) were used as the adhesive group, the bioadhesives' side in contact with the tissue built covalent anchors quickly to maintain the stability, but the superficial layer facing outward withstood fast hydrolysis and then lost its adhesion within minutes, avoiding the indiscriminate adhesiveness. In addition, because of the specific degradation behavior of succinyl ester, the SEgel with proper in vivo retention was achieved without the worry of causing foreign body reactions and unexpected tissue adhesion. Both the cecum-sidewall adhesion and hepatic adhesion models showed that the SEgel markedly reduced the severity of tissue adhesion. These results, together with the ease of the preparation process and well-proven biocompatibility of raw materials, revealed that the SEgel might be a promising solution for postoperative antiadhesion.

Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.

Biomaterials-assisted exosomes therapy in osteoarthritis.

Due to the avascular characteristic of articular cartilage, its self-repair capacity is limited. When cartilage is damaged or forms osteoarthritis (OA), clinical treatment is necessary. However, conventional treatments, including joint replacement, microfracture, cell and drug therapies, have certain limits. Lately, the exosomes derived from mesenchymal stem cells (MSCs-EXO), which consist of complex transcription factors, proteins and targeting ligand components, have shown great therapeutic potentials. With recent advancements in various biomaterials to extend MSCs-EXO's retention time and control the release propertiesin vivo, biomaterials-assisted exosomes therapy has been soon becoming a practically powerful tool in treating OA. This review analyzes the effects of MSCs-EXO on OA inflammation, metabolism, ageing and apoptosis, and introduces the combinational systems of MSCs-EXO with biomaterials to enhance the repair, anti-inflammatory, and homeostasis regulation functions. Moreover, different types of natural or synthetic biomaterials and their applications with MSCs-EXO were also described and discussed. And finally, we presage the future perspective in the development of biomaterial-assisted exosome therapies, as well as the potential to incorporate with other treatments to enhance their therapeutic effects in OA.

Visualization of Acute Inflammation through a Macrophage-Camouflaged Afterglow Nanocomplex.

Acute inflammation is a basic innate, immediate, and stereotyped immune response to injury, which is characterized by rapid recruitment of immune cells to the vasculature and extravasation into the damaged parenchyma. Visualization of acute inflammation plays an important role in monitoring the disease course and understanding pathogenesis, which lacks specific targeted and observing tools in vivo. Here, we report a Trojan horse strategy of a macrophage-camouflaged afterglow nanocomplex (UCANPs@RAW) to specifically visualize acute inflammation. Due to the advantages of optical antibackground interference elimination, as well as particular immune homing and long-term tracking capacity, UCANPs@RAW demonstrates an excellent acute inflammatory recognition ability. In an arthritis model, previously intravenously injected UCANPs@RAW could directionally migrate from the liver to the inflammation site as soon as 3 h after the model was induced, which could be continuously lighted for at least 36 h with the highest imaging signal-to-background ratio (SBR) as 382 at the time point of 9 h. Additionally, UCANPs@RAW is observed to penetrate the blood-brain barrier and image the deep brain inflamed region covered by the thick skull in an acute brain inflammation model with an SBRmax of 258, which is based on the strong recruiting ability of macrophages to immune response. In view of this smart nanocomplex, our strategy holds great potential for inflammatory detection and treatments.

Self-Delivery Janus-Prodrug for Precise Immuno-Chemotherapy of Colitis-Associated Colorectal Cancer.

Aromatized thioketal (ATK) linked the immunoregulatory molecule (budesonide, Bud) and the cytotoxic molecule (gemcitabine, Gem) to construct a ROS-activated Janus-prodrug, termed as BAG. Benefiting from the hydrogen bonding, π-π stacking, and other intermolecular interactions, BAG could self-assemble into nanoaggregates (BAG NA) with a well-defined spherical shape and uniform size distribution. Compared to the carrier-based drug delivery system, BAG NA have ultrahigh drug loading content and ROS concentration-dependent drug release. Colitis-associated colorectal cancer (CAC) is a typical disease in which chronic inflammation transforms into tumors. BAG NA can be internalized by colon cancer C26 cells and then triggered by excessive intracellular ROS to release nearly 100% of the drugs. Based on this, BAG NA showed a stronger pro-apoptotic effect than free Bud combined with free Gem. What is gratifying is that orally administered BAG NA can precisely accumulate in the diseased colon tissues of CAC mice induced by AOM/DSS and simultaneously release Bud and Gem. Bud can regulate the tumor immune microenvironment to restore and enhance the cytotoxicity of Gem. Therefore, BAG NA maximizes the synergistic therapeutic effect through co-delivery of Bud and Gem. This work provided a cutting-edge method for constructing self-delivery Janus-prodrug based on ATK and confirmed its potential application in inflammation-related carcinogenesis.

A dual-functional chitosan derivative platform for fungal keratitis.

Fungal keratitis remains a serious infectious ocular disease, and the traditional administration of eye drops is limited by ocular intrinsic barriers and drug shortages. Herein, we fabricated a chitosan-based dual-functional platform for ocular topical delivery of econazole. The platform can prolong the residence time on the ocular surface due to its strong interaction with the mucin layer by physical adhesion and covalent bonding, and also open corneal epithelial tight junctions for being positively charged, thereby enhancing corneal penetration of drug. Using these strategies, dosing concentration was reduced from 0.3 wt% to 0.1 wt%, dosing frequency was reduced from once-an-hour to twice-daily, in vitro and in vivo antifungal therapeutic effects were achieved and patient compliance could be improved. Given its high structural adaptability, many other ocular anterior segment-related diseases would benefit from this platform.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy.

Chitosan is one of the most studied natural origin polymers for biomedical applications. This review focuses on the potential of chitosan in localized antimicrobial therapy to address the challenges of current rising antimicrobial resistance. Due to its mucoadhesiveness, chitosan offers the opportunity to prolong the formulation residence time at mucosal sites; its wound healing properties open possibilities to utilize chitosan as wound dressings with multitargeted activities and more. We provide an unbiased overview of the state-of-the-art chitosan-based delivery systems categorized by the administration site, addressing the site-related challenges and evaluating the representative formulations. Specifically, we offer an in-depth analysis of the current challenges of the chitosan-based novel delivery systems for skin and vaginal infections, including its formulations optimizations and limitations. A brief overview of chitosan's potential in treating ocular, buccal and dental, and nasal infections is included. We close the review with remarks on toxicity issues and remaining challenges and perspectives.

Discovery of novel phenaleno isoquinolinium-based fluorescence imaging agents for sentinel lymph node mapping.

Fluorescence imaging agents have recently received huge attention due to their important role in disease diagnostics. However, the intrinsic problems of these probes, such as complex synthetic routes and high molecular weight, remain challenging. Here, we developed novel phenaleno isoquinolinium-based fluorescent agents, Medical Fluorophores 37-41 (MF37-41), applicable to the quantitative and sensitive detection of sentinel lymph nodes (SLNs). These imaging agents showed no adverse effects on the proliferation of immune and normal cells and did not induce in vivo toxicity. In vivo fluorescence lifetime imaging demonstrated the accumulation of phenaleno isoquinolinium salts in the SLNs of nude mice within 15 min postinjection, consistent with our biodistribution findings. These results suggest that phenaleno isoquinolinium salts are feasible fluorescence imaging agents that can be used as potential lymphatic tracers.

Enhanced wound healing properties of guar gum/curcumin-stabilized silver nanoparticle hydrogels.

Biocompatible materials that act as scaffolds for regenerative medicine are of enormous interest. Hydrogel-nanoparticle composites have great potential in this regard, however evaluations of their wound healing and safety in vivo in animal studies are scarce. Here we demonstrate that a guar gum/curcumin-stabilized silver nanoparticle hydrogel composite is an injectable material with exceptional wound healing and antibacterial properties. We show that the curcumin-bound silver nanoparticles themselves exhibit low cytotoxicity and enhance proliferation, migration, and collagen production in in vitro studies of human dermal fibroblasts. We then show that the hydrogel-nanoparticle composite promotes wound healing in in vivo studies on rats, accelerating wound closure by > 40% and reducing bacterial counts by 60% compared to commercial antibacterial gels. Histopathology indicates that the hydrogel composite enhances transition from the inflammation to proliferation stage of healing, promoting the formation of fibroblasts and new blood vessels, while target gene expression studies confirm that the accelerated tissue remodeling occurs along the normal pathways. As such these hydrogel composites show great promise as wound dressing materials with high antibacterial capacity.

In Situ Nanotransformable Hydrogel for Chemo-Photothermal Therapy of Localized Tumors and Targeted Therapy of Highly Metastatic Tumors.

Metastasis is one of the predisposing factors for cancer-related mortalities worldwide. Patients with advanced cancers (stage IV) receive palliative care with minimal possibility of achieving complete remission. Antibody-based therapeutic modalities are capable of targeting tumors that are confined to a particular location but are ineffective in targeting distant secondary tumors. In the current study, we have developed a smart nano-transforming hydrogel (NTG) that transforms in situ to polymeric nanoparticles (PA NPs) of 100-150 nm when injected subcutaneously. These nanoparticles targeted the primary and secondary metastatic tumors for up to ∼5 and ∼3 days, respectively. The in situ-formed PA NPs also demonstrated a pH-responsive drug release resulting in about ∼80% release within 100 h at 5.8 pH. When tested in vivo, substantial inhibition of lung metastases was observed compared to chemotherapy, thus demonstrating the efficiency of nanotransforming hydrogels in targeting and inhibiting primary and secondary metastatic tumors.

Biocompatible All-in-One Adhesive Needle-Free Cup Patch for Enhancing Transdermal Drug Delivery.

Patch-type drug delivery has garnered increased attention as an attractive alternative to the existing drug delivery techniques. Thus far, needle phobia and efficient drug delivery remain huge challenges. To address the issue of needle phobia and enhance drug delivery, we developed a needle-free and self-adhesive microcup patch that can be loaded with an ultrathin salmon DNA (SDNA) drug carrier film. This physically integrated system can facilitate efficient skin penetration of drugs loaded into the microcup patch. The system consists of three main components, namely, a cup that acts as a drug reservoir, an adhesive system that attaches the patch to the skin, and physical stimulants that can be used to increase the efficiency of drug delivery. In addition, an ultrathin SDNA/drug film allows the retention of the drug in the cup and its efficient release by dissolution in the presence of moisture. This latter feature has been validated using gelatin as a skin mimic. The cup design itself has been validated by comparing its deformation and displacement with those of a cylindrical structure. Integration of the self-adhesive microcup patch with both ultrasonic waves and an electric current allows the model drug to penetrate the stratum corneum of the skin barrier and the whole epidermis, thereby enhancing transdermal drug delivery and reducing skin irritation. This system can be used as a wearable biomedical device for efficient transdermal and needle-free drug delivery.

Functionalization of filled radioactive multi-walled carbon nanocapsules by arylation reaction for in vivo delivery of radio-therapy.

Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (152SmCl3), the ends of the MWCNTs are sealed by high temperature treatment, and the encapsulated 152Sm is neutron activated to radioactive 153Sm. The external walls of the radioactive nanocapsules are functionalized through arylation reaction, to introduce hydrophilic chains and increase the water dispersibility of CNTs. The organ biodistribution profiles of the nanocapsules up to 24 h are assessed in naïve mice and different tumor models in vivo. By quantitative γ-counting, 153SmCl3@MWCNTs-NH2 exhibite high accumulation in organs without leakage of the internal radioactive material to the bloodstream. In the treated mice, highest uptake is detected in the lung followed by the liver and spleen. Presence of tumors in brain or lung does not increase percentage accumulation of 153SmCl3@MWCNTs-NH2 in the respective organs, suggesting the absence of the enhanced permeation and retention effect. This study presents a chemical functionalization protocol that is rapid (∼one hour) and can be applied to filled radioactive multi-walled carbon nanocapsules to improve their water dispersibility for systemic administration for their use in targeted radiotherapy.

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.