Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.
- Klíčová slova
- computed tomography contrast agent, implant, light‐based 3D printing, light‐based crosslinking, photo‐crosslinkable polymers, polyester, thiol‐ene step growth polymerization,
- MeSH
- biokompatibilní materiály chemie MeSH
- myši MeSH
- polyestery * chemie MeSH
- poréznost MeSH
- testování materiálů MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury * chemie MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- polycaprolactone MeSH Prohlížeč
- polyestery * MeSH
Herein, the recent advances in the development of resorbable polymeric-based biomaterials, their geometrical forms, resorption mechanisms, and their capabilities in various biomedical applications are critically reviewed. A comprehensive discussion of the engineering approaches for the fabrication of polymeric resorbable scaffolds for tissue engineering, drug delivery, surgical, cardiological, aesthetical, dental and cardiovascular applications, are also explained. Furthermore, to understand the internal structures of resorbable scaffolds, representative studies of their evaluation by medical imaging techniques, e.g., cardiac computer tomography, are succinctly highlighted. This approach provides crucial clinical insights which help to improve the materials' suitable and viable characteristics for them to meet the highly restrictive medical requirements. Finally, the aspects of the legal regulations and the associated challenges in translating research into desirable clinical and marketable materials of polymeric-based formulations, are presented.
- Klíčová slova
- clinical challenges, drug delivery, implants, medical imaging, polymer matrices, resorbable biomaterials, tissue engineering,
- MeSH
- biokompatibilní materiály chemie MeSH
- lidé MeSH
- polymery * chemie MeSH
- systémy cílené aplikace léků * metody MeSH
- tkáňové inženýrství * metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- polymery * MeSH
Neurostimulation employing photoactive organic semiconductors offers an appealing alternative to conventional techniques, enabling targeted action and wireless control through light. In this study, organic electrolytic photocapacitors (OEPC) are employed to investigate the effects of light-controlled electric stimulation on neuronal networks in vitro and in vivo. The interactions between the devices and biological systems are characterized. Stimulation of primary rat cortical neurons results in an elevated expression of c-Fos within a mature neuronal network. OEPC implantation for three weeks and subsequent stimulation of the somatosensory cortex leads to an increase of c-Fos in neurons at the stimulation site and in connected brain regions (entorhinal cortex, hippocampus), both in the ipsi- and contralateral hemispheres. Reactivity of glial and immune cells after semi-chronic implantation of OEPC in the rat brain is comparable to that of surgical controls, indicating minimal foreign body response. Device functionality is further substantiated through retained charging dynamics following explantation. OEPC-based, light-controlled electric stimulation has a significant impact on neural responsiveness. The absence of detrimental effects on both the brain and device encourages further use of OEPC as cortical implants. These findings highlight its potential as a novel mode of neurostimulation and instigate further exploration into applications in fundamental neuroscience.
- Klíčová slova
- bioelectronics, cortical stimulation, c‐Fos, excitability, immunohistochemistry, organic semiconductors, wireless stimulation,
- MeSH
- elektrická stimulace * metody MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- nervová síť fyziologie MeSH
- neurony * metabolismus fyziologie MeSH
- polovodiče MeSH
- potkani Sprague-Dawley MeSH
- světlo MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Platinum is the most widespread electrode material used for implantable biomedical and neuroelectronic devices, motivating exploring ways to improve its performance and understand its fundamental properties. Using reactive magnetron sputtering, PtOx is prepared, which upon partial reduction yields a porous thin-film form of platinum with favorable properties, notably record-low impedance values outcompeting other reports for platinum-based electrodes. It is established that its high electrochemical capacitance scales with thickness, in the way of volumetric capacitor materials like IrOx and poly(3,4-ethylenedioxythiophene), PEDOT. Unlike these two well-known analogs, however, it is found that PtOx capacitance is not caused by reversible pseudofaradaic reactions but rather due to high surface area. In contrast to IrOx, PtOx is not a reversible valence-change oxide, but rather a porous form of platinum. The findings show that this oxygen-containing form of Pt can place Pt electrodes on a level competitive with IrOx and PEDOT. Due to its relatively low cost and ease of preparation, PtOx can be a good choice for microfabricated bioelectronic devices.
- Klíčová slova
- bioelectronics, biomedical microdevices, electrochemistry, platinum, reactive sputtering,
- MeSH
- bicyklické sloučeniny heterocyklické * chemie MeSH
- elektrická kapacitance * MeSH
- elektrody * MeSH
- platina * chemie MeSH
- polymery chemie MeSH
- poréznost MeSH
- povrchové vlastnosti MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bicyklické sloučeniny heterocyklické * MeSH
- platina * MeSH
- poly(3,4-ethylene dioxythiophene) MeSH Prohlížeč
- polymery MeSH
Plasmalogens (vinyl-ether phospholipids) are an emergent class of lipid drugs against various diseases involving neuro-inflammation, oxidative stress, mitochondrial dysfunction, and altered lipid metabolism. They can activate neurotrophic and neuroprotective signaling pathways but low bioavailabilities limit their efficiency in curing neurodegeneration. Here, liquid crystalline lipid nanoparticles (LNPs) are created for the protection and non-invasive intranasal delivery of purified scallop-derived plasmalogens. The in vivo results with a transgenic mouse Parkinson's disease (PD) model (characterized by motor impairments and α-synuclein deposition) demonstrate the crucial importance of LNP composition, which determines the self-assembled nanostructure type. Vesicle and hexosome nanostructures (characterized by small-angle X-ray scattering) display different efficacy of the nanomedicine-mediated recovery of motor function, lipid balance, and transcriptional regulation (e.g., reduced neuro-inflammation and PD pathogenic gene expression). Intranasal vesicular and hexosomal plasmalogen-based LNP treatment leads to improvement of the behavioral PD symptoms and downregulation of the Il6, Il33, and Tnfa genes. Moreover, RNA-sequencing and lipidomic analyses establish a dramatic effect of hexosomal nanomedicines on PD amelioration, lipid metabolism, and the type and number of responsive transcripts that may be implicated in neuroregeneration.
- Klíčová slova
- RNA‐seq, hexosomes, in vivo Parkinson's disease transgenic mouse model, liquid crystalline lipid nanoparticles, nanomedicine,
- MeSH
- aplikace intranazální * MeSH
- liposomy MeSH
- metabolismus lipidů účinky léků MeSH
- modely nemocí na zvířatech * MeSH
- myši transgenní MeSH
- myši MeSH
- nanočástice * chemie MeSH
- nanomedicína * metody MeSH
- Parkinsonova nemoc * metabolismus farmakoterapie MeSH
- plasmalogeny * chemie farmakologie MeSH
- regulace genové exprese účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Lipid Nanoparticles MeSH Prohlížeč
- liposomy MeSH
- plasmalogeny * MeSH
Nano-sized carriers are widely studied as suitable candidates for the advanced delivery of various bioactive molecules such as drugs and diagnostics. Herein, the development of long-circulating stimuli-responsive polymer nanoprobes tailored for the fluorescently-guided surgery of solid tumors is reported. Nanoprobes are designed as long-circulating nanosystems preferably accumulated in solid tumors due to the Enhanced permeability and retention effect, so they act as a tumor microenvironment-sensitive activatable diagnostic. This study designs polymer probes differing in the structure of the spacer between the polymer carrier and Cy7 by employing pH-sensitive spacers, oligopeptide spacers susceptible to cathepsin B-catalyzed enzymatic hydrolysis, and non-degradable control spacer. Increased accumulation of the nanoprobes in the tumor tissue coupled with stimuli-sensitive release behavior and subsequent activation of the fluorescent signal upon dye release facilitated favorable tumor-to-background ratio, a key feature for fluorescence-guided surgery. The probes show excellent diagnostic potential for the surgical removal of intraperitoneal metastasis and orthotopic head and neck tumors with very high efficacy and accuracy. In addition, the combination of macroscopic resection followed by fluorescence-guided surgery using developed probes enable the identification and resection of most of the CAL33 intraperitoneal metastases with total tumor burden reduced to 97.2%.
- Klíčová slova
- HPMA copolymers, fluorescence, guided surgery, polymer probes, stimuli-sensitiveness,
- MeSH
- chytré polymery * MeSH
- fluorescence MeSH
- fluorescenční barviva chemie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- nádory hlavy a krku * diagnostické zobrazování chirurgie MeSH
- polymery MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chytré polymery * MeSH
- fluorescenční barviva MeSH
- polymery MeSH
Traditional thrombolytic therapeutics for vascular blockage are affected by their limited penetration into thrombi, associated off-target side effects, and low bioavailability, leading to insufficient thrombolytic efficacy. It is hypothesized that these limitations can be overcome by the precisely controlled and targeted delivery of thrombolytic therapeutics. A theranostic platform is developed that is biocompatible, fluorescent, magnetic, and well-characterized, with multiple targeting modes. This multimodal theranostic system can be remotely visualized and magnetically guided toward thrombi, noninvasively irradiated by near-infrared (NIR) phototherapies, and remotely activated by actuated magnets for additional mechanical therapy. Magnetic guidance can also improve the penetration of nanomedicines into thrombi. In a mouse model of thrombosis, the thrombosis residues are reduced by ≈80% and with no risk of side effects or of secondary embolization. This strategy not only enables the progression of thrombolysis but also accelerates the lysis rate, thereby facilitating its prospective use in time-critical thrombolytic treatment.
- Klíčová slova
- biomarkers, cold atmospheric plasma, multimodal theranostic, nanoclusters, photo/magnetic thrombolysis,
- MeSH
- fibrinolytika chemie terapeutické užití MeSH
- individualizovaná medicína MeSH
- magnetické jevy MeSH
- myši MeSH
- trombolytická terapie * MeSH
- trombóza * diagnostické zobrazování farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fibrinolytika MeSH
Magnetic nanorobots offer wireless navigation capability in hard-to-reach areas of the human body for targeted therapy and diagnosis. Though in vivo imaging is required for guidance of the magnetic nanorobots toward the target areas, most of the imaging techniques are inadequate to reveal the potential locomotion routes. This work proposes the use of radiopaque magnetic nanorobots along with microcomputed tomography (microCT) for localized in vivo imaging applications. The nanorobots consist of a contrast agent, barium sulfate (BaSO4 ), magnetized by the decoration of magnetite (Fe3 O4 ) particles. The magnetic features lead to actuation under rotating magnetic fields and enable precise navigation in a microfluidic channel used to simulate confined spaces of the body. In this channel, the intrinsic radiopacity of the nanorobots also provides the possibility to reveal the internal structures by X-ray contrast. Furthermore, in vitro analysis indicates nontoxicity of the nanorobots. In vivo experiments demonstrate localization of the nanorobots in a specific part of the gastrointestinal (GI) tract upon the influence of the magnetic field, indicating the efficient control even in the presence of natural peristaltic movements. The nanorobots reported here highlight that smart nanorobotic contrast agents can improve the current imaging-based diagnosis techniques by providing untethered controllability in vivo.
- Klíčová slova
- computed tomography, gastrointestinal tract, magnetic actuation, medical imaging, nanomotors, nanoswimmers, tracking,
- MeSH
- gastrointestinální trakt * diagnostické zobrazování MeSH
- kontrastní látky * chemie MeSH
- lidé MeSH
- magnetismus MeSH
- rentgenová mikrotomografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kontrastní látky * MeSH
Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.
- Klíčová slova
- LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
- MeSH
- myši MeSH
- polymery * MeSH
- teplota MeSH
- tkáňová distribuce MeSH
- uvolňování léčiv MeSH
- voda * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- polymery * MeSH
- voda * MeSH
Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques.
- Klíčová slova
- bioelectronic medicines, electrical stimulation, flexible electronics, neurostimulation, temporal interference, transcutaneous,
- MeSH
- elektrická stimulace MeSH
- myši MeSH
- nervus ischiadicus fyziologie MeSH
- transkutánní elektrická neurostimulace * metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
