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Biodegradable segmented polyurethanes were prepared with poly(caprolactone) diol as a soft segment, 4,4′-methylene bis(cyclohexyl isocyanate) (HMDI) and either butanediol or dithioerythritol as chain extenders. Platelet adhesion was similar in all segmented polyurethanes studied and not different from Tecoflex® although an early stage of activation was observed on biodegradable segmented polyurethane prepared with dithioerythritol. Relative viability was higher than 80% on human umbilical vein endothelial cells in contact with biodegradable segmented polyurethane extracts after 1, 2 and 7 days. Furthermore, both biodegradable segmented polyurethane materials supported human umbilical vein endothelial cell adhesion, spreading, and viability similar to Tecoflex® medical-grade polyurethane. These biodegradable segmented polyurethanes represent promising materials for cardiovascular applications. [ABSTRACT FROM AUTHOR]

Plasma-based sterilization is a promising alternative to the use of pure ethylene oxide (EO), for low-temperature clinical sterilization of medical instruments and devices. However, few studies have been published that evaluate its safety in terms of possible damage to materials, particularly polymers. The objective of this work was to evaluate polymer surface modifications induced by commercial plasma-based sterilizers, in comparison with pure EO: Samples from 5 polymer-based devices were subjected to 1, 5, and 10 sterilization cycles by Sterrad-100 [ABSTRACT FROM AUTHOR]

When nanoparticle delivery systems are immersed in biological fluids, a complex assembly of proteins forms on their surface, creating a protein corona. The protein corona alters the physicochemical properties, toxicity, biodistribution, cellular uptake, and immune response of the nanoparticles, and consequently, their therapeutic efficacy. Currently, there is a lack of in vitro methods to assess the effects of the protein corona on nanoparticle uptake under dynamic flow and assess their binding kinetics in real-time. Here, we introduce quartz crystal microbalance with dissipation (QCM-D) as an in vitro technique, capable of incorporating dynamic flow, to study the effect of the protein corona on the binding of nanoliposome (NLP) formulations to cell surfaces as a first step in their cellular uptake. The interactions of four NLP formulations (low PEGylated, high PEGylated, negatively charged and positively charged NLPs) with A375 melanoma and THP1 cell lines were assessed by QCM-D, before and after the formation of a protein corona. Through real-time recording of the frequency and dissipation shifts (Δ f and Δ D , respectively), the QCM-D results provided strong evidence of the role of the protein corona in the cellular interaction of these NLP formulations, with a variation in their adsorption kinetics depending on their initial composition. NLP's attachment to the cell surface was the lowest for PEGylated NLPs (<5%), while the positively charged NLPs showed the highest cellular attachment (≈100%), regardless of the presence of the protein corona or cell type. The effect of the protein corona was more pronounced for the negatively charged NLPs, where a significant reduction in the NLP attachment was observed. To complement the QCM-D data on the NLP attachment and to determine whether the NLP attachment leads to cellular uptake, confocal microscopy and flow cytometry were used to confirm NLP uptake by A375 and THP1 cells. Proteomic analysis revealed a differential composition of the protein corona on the various NLPs with possible implications for their sequestration and cellular uptake. Collectively, the findings suggest that QCM-D can be an important tool to study the binding of NLP formulations or other nanoparticles with cell membranes under dynamic flow, which very often differs from nanoparticle uptake under static conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Multilayer conformal coatings have been shown to provide a nanoscale barrier between cells and their environment with adequate stability, while regulating the diffusion of nutrition and waste across the cell membrane. The coating method aims to minimize capsule thickness and implant volume while reducing the need for immunosuppressive drugs, making it a promising approach for islet cell encapsulation in clinical islet transplantation for the treatment of Type 1 diabetes. This study introduces an immunoprotective nanocoating obtained through electrostatic interaction between quaternized phosphocholine-chitosan (PC-QCH) and tetrahydropyran triazole phenyl-alginate (TZ-AL) onto mouse β-cell spheroids. First, successful synthesis of the proposed polyelectrolytes was confirmed with physico-chemical characterization. A coating with an average thickness of 540 nm was obtained with self-assembly of 4-bilayers of PC-QCH/TZ-AL onto MIN6 β-cell spheroids. Surface coating of spheroids did not affect cell viability, metabolic activity, or insulin secretion, when compared to non-coated spheroids. The exposure of the polyelectrolytes to THP-1 monocyte-derived macrophages lead to a reduced level of TNF-α secretion and exposure of coated spheroids to RAW264.7 macrophages showed a decreasing trend in the secretion of TNF-α and IL-6. In addition, coated spheroids were able to establish normoglycemia when implanted into diabetic NOD-SCID mice, demonstrating in vivo biocompatibility and cellular function. These results demonstrate the ability of the PC-QCH/TZ-AL conformal coating to mitigate pro-inflammatory responses from macrophages, and thus can be a promising candidate towards nanoencapsulation for cell-based therapy, particularly in type 1 diabetes, where the insulin secreting β-cells are subjected to inflammation and immune cell attack., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Human vocal folds (VFs), a pair of small, soft tissues in the larynx, have a layered mucosal structure with unique mechanical strength to support high-level tissue deformation by phonation. Severe pathological changes to VF have causes including surgery, trauma, age-related atrophy, and radiation, and lead to partial or complete communication loss and difficulty in breathing and swallowing. VF glottal insufficiency requires injectable VF biomaterials such as hyaluronan, calcium hydroxyapatite, and autologous fat to augment VF functions. Although these biomaterials provide an effective short-term solution, significant variations in patient response and requirements of repeat reinjection remain notable challenges in clinical practice. Tissue engineering strategies have been actively explored in the search of an injectable biomaterial that possesses the capacity to match native tissue's material properties while promoting permanent tissue regeneration. This review aims to assess the current status of biomaterial development in VF tissue engineering. The focus will be on examining state-of-the-art techniques including modification with bioactive molecules, cell encapsulation, composite materials, and in situ crosslinking with click chemistry. We will discuss potential opportunities that can further leverage these engineering techniques in the advancement of VF injectable biomaterials. Impact Statement Injectable vocal fold (VF) biomaterials augment tissue function through minimally invasive procedures, yet there remains a need for long-term VF reparation. This article reviews cutting-edge research in VF biomaterial development to propose safe and effective tissue engineering strategies for improving regenerative outcomes. Special focus is paid to methods to enhance bioactivity and achieve tissue-mimicking mechanical properties, longer in situ stability, and inherent biomaterial bioactivity.

Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane-bound vesicles are secreted by all cells carrying different cargos that can serve as both disease biomarkers and disease modifiers. Nonetheless, despite a significant peak in research regarding EVs as OA therapeutics, clinical implementation seems distant. In addition to scalability and standardization challenges, researchers often omit to focus on and consider the proper tropism of the vesicles, the practicality and relevance of their source, their low native therapeutic efficacy, and whether they address the disease as a whole. These considerations are necessary to better understand EVs in a clinical light and have been comprehensively discussed and ultimately summarized in this review into a conceptualized framework termed the nanodiamond concept. Future perspectives are also discussed, and alternatives are presented to address some of the challenges and concerns., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

In vitro drug screening for type 1 diabetes therapies has largely been conducted on human organ donor islets for proof of efficacy. While native islets are the ultimate target of these drugs (either in situ or for transplantation), significant benefit can be difficult to ascertain due to the highly heterogeneous nature of individual donors and the overall scarcity of human islets for research. We present an in vitro coculture model based on immortalized insulin-producing beta-cell lines with human endothelial cells in 3D spheroids that aims to recapitulate the islet morphology in an effort towards developing a standardized cell model for in vitro diabetes research. Human insulin-producing immortalized EndoC- β H5 cells are cocultured with human endothelial cells in varying ratios to evaluate 3D cell culture models for type 1 diabetes research. Insulin secretion, metabolic activity, live cell fluorescence staining, and gene expression assays were used to compare the viability and functionality of spheroids composed of 100% beta-cells, 1 : 1 beta-cell/endothelial, and 1 : 3 beta-cell/endothelial. Monoculture and β H5/HUVEC cocultures formed compact spheroids within 7 days, with average diameter ~140  μ m. This pilot study indicated that stimulated insulin release from 0 to 20 mM glucose increased from ~8-fold for monoculture and 1 : 1 coculture spheroids to over 20-fold for 1 : 3 EndoC- β H5/HUVEC spheroids. Metabolic activity was also ~12% higher in the 1 : 3 EndoC- β H5/HUVEC group compared to other groups. Stimulating monoculture beta-cell spheroids with 20 mM glucose +1  μ g/mL glycine-modified INGAP-P increased the insulin stimulation index ~2-fold compared to glucose alone. Considering their availability and consistent phenotype, EndoC- β H5-based spheroids present a useful 3D cell model for in vitro testing and drug screening applications., Competing Interests: The authors declare that they have no conflicts of interest regarding this manuscript., (Copyright © 2023 James M. Porter et al.)

Lipid nanoparticles (LNPs) are biocompatible drug delivery systems that have found numerous applications in medicine. Their versatile nature enables the encapsulation and targeting of various types of medically relevant molecular cargo, including oligonucleotides, proteins, and small molecules for the treatment of diseases, such as cancer. Cancers that form solid tumors are particularly relevant for LNP-based therapeutics due to the enhanced permeation and retention effect that allows nanoparticles to accumulate within the tumor tissue. Additionally, LNPs can be formulated for both locoregional and systemic delivery depending on the tumor type and stage. To date, LNPs have been used extensively in the clinic to reduce systemic toxicity and improve outcomes in cancer patients by encapsulating chemotherapeutic drugs. Next-generation lipid nanoparticles are currently being developed to expand their use in gene therapy and immunotherapy, as well as to enable the co-encapsulation of multiple drugs in a single system. Other developments include the design of targeted LNPs to specific cells and tissues, and triggerable release systems to control cargo delivery at the tumor site. This review paper highlights recent developments in LNP drug delivery formulations and focuses on the treatment of solid tumors, while also discussing some of their current translational limitations and potential opportunities in the field., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Bioactive surface coatings have retained the attention of researchers and physicians due to their versatility and range of applications in orthopedics, particularly in infection prevention. Antibacterial metal nanoparticles (mNPs) are a promising therapeutic, with vast application opportunities on orthopedic implants. The current research aimed to construct a polyelectrolyte multilayer on a highly porous titanium implant using alternating thin film coatings of chitosan and alginate via the layer-by-layer (LbL) self-assembly technique, along with the incorporation of silver nanoparticles (AgNPs) or titanium dioxide nanoparticles (TiO 2 NPs), for antibacterial and osteoconductive activity. These mNPs were characterized for their physicochemical properties using quartz crystal microgravimetry with a dissipation system, nanoparticle tracking analysis, scanning electron microscopy, and atomic force microscopy. Their cytotoxicity and osteogenic differentiation capabilities were assessed using AlamarBlue and alkaline phosphatase (ALP) activity assays, respectively. The antibiofilm efficacy of the mNPs was tested against Staphylococcus aureus . The LbL polyelectrolyte coating was successfully applied to the porous titanium substrate. A dose-dependent relationship between nanoparticle concentration and ALP as well as antibacterial effects was observed. TiO 2 NP samples were also less cytotoxic than their AgNP counterparts, although similarly antimicrobial. Together, these data serve as a proof-of-concept for a novel coating approach for orthopedic implants with antimicrobial and osteoconductive properties.

Bone-mimicking scaffolds based on silk fibroin (SF) mixed with hydroxyapatite nanoparticles (HA NPs) and titanium oxide (TiO 2 ) nanoparticles were created as materials for bone formation. Six scaffold groups were fabricated: S1 (SF), S2 (Silk + (HA: TiO 2 ; 100: 0)), S3 (Silk, (HA: TiO 2 ; 70: 30)), S4 (Silk + (HA NPs: TiO 2 ; 50: 50)), S5 (Silk + (HA: TiO 2 ; 30: 70)), and S6 (Silk + (HA NPs: TiO 2 ; 0:100)). Scaffolds were characterized for molecular formation, structure, and morphology by Fourier transform infrared spectroscopy, element analysis, and X-ray diffraction. They were tested for physical swelling and compressive modulus. Scaffolds were cultured with MC3T3 and tested in vitro to evaluate their biological performance. The results showed that scaffolds with HA and TiO 2 demonstrated molecular interaction via amide I and phosphate groups. These scaffolds had smaller pore sizes than those without HA and TiO 2 . They showed more swelling and higher compressive modulus than the scaffolds without HA and TiO 2 . They exhibited better biological performance: cell adhesion, viability, proliferation, alkaline phosphatase activity, and calcium content than the scaffolds without HA and TiO 2 . Their porous walls acted as templates for cell aggregation and supported synthesis of calcium secreted from cells. S3 were the most suitable scaffolds. With their enhanced osteo-conductive function, they are promising for bone augmentation for oral and maxillofacial surgery., (© 2023 IOP Publishing Ltd.)

An increasing number of publications over the past ten years have focused on the development of chitosan-based cross-linked scaffolds to regenerate bone tissue. The design of biomaterials for bone tissue engineering applications relies heavily on the ideals set forth by a polytherapy approach called the "Diamond Concept". This methodology takes into consideration the mechanical environment, scaffold properties, osteogenic and angiogenic potential of cells, and benefits of osteoinductive mediator encapsulation. The following review presents a comprehensive summarization of recent trends in chitosan-based cross-linked scaffold development within the scope of the Diamond Concept, particularly for nonload-bearing bone repair. A standardized methodology for material characterization, along with assessment of in vitro and in vivo potential for bone regeneration, is presented based on approaches in the literature, and future directions of the field are discussed.

Current delivery of chemotherapy, either intra-venous or intra-arterial, remains suboptimal for patients with head and neck tumors. The free form of chemotherapy drugs, such as docetaxel, has non-specific tissue targeting and poor solubility in blood that deters treatment efficacy. Upon reaching the tumors, these drugs can also be easily washed away by the interstitial fluids. Liposomes have been used as nanocarriers to enhance docetaxel bioavailability. However, they are affected by potential interstitial dislodging due to insufficient intratumoral permeability and retention capabilities. Here, we developed and characterized docetaxel-loaded anionic nanoliposomes coated with a layer of mucoadhesive chitosan (chitosomes) for the application of chemotherapy drug delivery. The anionic liposomes were 99.4 ± 1.5 nm in diameter with a zeta potential of -26 ± 2.0 mV. The chitosan coating increased the liposome size to 120 ± 2.2 nm and the surface charge to 24.8 ± 2.6 mV. Chitosome formation was confirmed via FTIR spectroscopy and mucoadhesive analysis with anionic mucin dispersions. Blank liposomes and chitosomes showed no cytotoxic effect on human laryngeal stromal and cancer cells. Chitosomes were also internalized into the cytoplasm of human laryngeal cancer cells, indicating effective nanocarrier delivery. A higher cytotoxicity ( p < 0.05) of docetaxel-loaded chitosomes towards human laryngeal cancer cells was observed compared to human stromal cells and control treatments. No hemolytic effect was observed on human red blood cells after a 3 h exposure, proving the proposed intra-arterial administration. Our in vitro results supported the potential of docetaxel-loaded chitosomes for locoregional chemotherapy delivery to laryngeal cancer cells.

Nanotherapeutics, on their path to the target tissues, face numerous physicochemical hindrances that affect their therapeutic efficacy. Physical barriers become more pronounced in pathological tissues, such as solid tumors, where they limit the penetration of nanocarriers into deeper regions, thereby preventing the efficient delivery of drug cargo. To address this challenge, we introduce a novel approach that employs surface acoustic wave (SAW) technology to sonoprint and enhance the delivery of nanoparticles onto and into cell spheroids. Our SAW platform is designed to generate focused and unidirectional acoustic waves for creating vigorous acoustic streaming while promoting Bjerknes forces. The effect of SAW excitation on cell viability, as well as the accumulation and penetration of nanoparticles on human breast cancer (MCF 7) and mouse melanoma (YUMM 1.7) cell spheroids were investigated. The high frequency, low input voltage, and contact-free nature of the proposed SAW system ensured over 92% cell viability for both cell lines after SAW exposure. SAW sonoprinting enhanced the accumulation of 100 nm polystyrene particles on the periphery of the spheroids to near four-fold, while the penetration of nanoparticles into the core regions of the spheroids was improved up to three times. To demonstrate the effectiveness of our SAW platform on the efficacy of nanotherapeutics, the platform was used to deliver nanoliposomes encapsulated with the anti-cancer metal compound copper diethyldithiocarbamate (CuET) to MCF 7 and YUMM 1.7 cell spheroids. A three-fold increase in the cytotoxic activity of the drug was observed in spheroids under the effect of SAW, compared to controls. The capacity of SAW-based devices to be manufactured as minuscule wearable patches can offer highly controllable, localized, and continuous acoustic waves to enhance drug delivery efficiency to target tissues.