Implantable Patch of Oxidized Nanofibrillated Cellulose and Lysozyme Amyloid Nanofibrils for the Regeneration of Infarcted Myocardium Tissue and Local Delivery of RNA-Loaded Nanoparticles.

Biopolymeric implantable patches are popular scaffolds for myocardial regeneration applications. Besides being biocompatible, they can be tailored to have required properties and functionalities for this application. Recently, fibrillar biobased nanostructures prove to be valuable in the development of functional biomaterials for tissue regeneration applications. Here, periodate-oxidized nanofibrillated cellulose (OxNFC) is blended with lysozyme amyloid nanofibrils (LNFs) to prepare a self-crosslinkable patch for myocardial implantation. The OxNFC:LNFs patch shows superior wet mechanical properties (60 MPa for Young's modulus and 1.5 MPa for tensile stress at tensile strength), antioxidant activity (70% scavenging activity under 24 h), and bioresorbability ratio (80% under 91 days), when compared to the patches composed solely of NFC or OxNFC. These improvements are achieved while preserving the morphology, required thermal stability for sterilization, and biocompatibility toward rat cardiomyoblast cells. Additionally, both OxNFC and OxNFC:LNFs patches reveal the ability to act as efficient vehicles to deliver spermine modified acetalated dextran nanoparticles, loaded with small interfering RNA, with 80% of delivery after 5 days. This study highlights the value of simply blending OxNFC and LNFs, synergistically combining their key properties and functionalities, resulting in a biopolymeric patch that comprises valuable characteristics for myocardial regeneration applications.

Quantum Sensing of Free Radical Generation in Mitochondria of Single Heart Muscle Cells during Hypoxia and Reoxygenation.

Cells are damaged during hypoxia (blood supply deprivation) and reoxygenation (oxygen return). This damage occurs in conditions such as cardiovascular diseases, cancer, and organ transplantation, potentially harming the tissue and organs. The role of free radicals in cellular metabolic reprogramming under hypoxia is under debate, but their measurement is challenging due to their short lifespan and limited diffusion range. In this study, we employed a quantum sensing technique to measure the real-time production of free radicals at the subcellular level. We utilize fluorescent nanodiamonds (FNDs) that exhibit changes in their optical properties based on the surrounding magnetic noise. This way, we were able to detect the presence of free radicals. To specifically monitor radical generation near mitochondria, we coated the FNDs with an antibody targeting voltage-dependent anion channel 2 (anti-VDAC2), which is located in the outer membrane of mitochondria. We observed a significant increase in the radical load on the mitochondrial membrane when cells were exposed to hypoxia. Subsequently, during reoxygenation, the levels of radicals gradually decreased back to the normoxia state. Overall, by applying a quantum sensing technique, the connections among hypoxia, free radicals, and the cellular redox status has been revealed.

Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium.

Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance. Protein nanofibrils (NFs), such as lysozyme nanofibrils (LNFs), are proteic nanostructures with excellent mechanical performance and antioxidant activity, which can work as nanotemplates to produce metallic nanoparticles. Here, gold nanoparticles (AuNPs) were synthesized in situ in the presence of LNFs, and the obtained hybrid AuNPs@LNFs were incorporated into gelatin-hyaluronic acid (HA) hydrogels for myocardial regeneration applications. The resulting nanocomposite hydrogels showed improved rheological properties, mechanical resilience, antioxidant activity, and electrical conductivity, especially for the hydrogels containing AuNPs@LNFs. The swelling and bioresorbability ratios of these hydrogels are favorably adjusted at lower pH levels, which correspond to the ones in inflamed tissues. These improvements were observed while maintaining important properties, namely, injectability, biocompatibility, and the ability to release a model drug. Additionally, the presence of AuNPs allowed the hydrogels to be monitorable through computer tomography. This work demonstrates that LNFs and AuNPs@LNFs are excellent functional nanostructures to formulate injectable biopolymeric nanocomposite hydrogels for myocardial regeneration applications.

Biomimetic platelet membrane-coated nanoparticles for targeted therapy.

The development of cell membrane-modified biomimetic nanoparticles has extensively increased during the past years due to their exceptional biocompatibility, evasion from the immune system, and targeting ability. Known as a cutting-edge area of research in nanomedicine, such novel nanoplatforms can mimic different functions of the primary cells, while successfully delivering their cargos to the defect site with the aim of enhancing the therapeutic responses and reducing the side effects. Platelet is a key factor for haemostasis and a major player in wound healing, inflammation, and many other biological functions and pathological conditions. As a highly responsive cell, platelets can adapt to environment modifications and release several soluble biomolecules, such as growth factors, coagulant factors, and extracellular vesicles. Additionally, platelets are capable of immune system evasion, sub-endothelial adhesion, and pathogen interaction. These characteristics have inspired the design of several platelet membrane-coated nanoparticles as drug delivery systems. This review describes the current developments in platelet membrane-coated nanoparticles for targeted therapy, specifically, their advantages compared to other biomimetic cell-derived nanoparticles and their applicability in the medical field are elucidated. Finally, the challenges and future perspectives associated with this nanoplatform are summarised.

Novel missense mutations affecting the structure of the conserved fibrinogen Bß C-terminal domain cause congenital hypofibrinogenemia.

This study describes the identification of two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency. Modelling of the impact of the mutations predict that these single amino acid substitutions are sufficient to abolish secretion of the mutant chains into the circulation, resulting in low fibrinogen levels in the patients. In addition, whole exome sequencing identified genetic modifiers for both patients which could contribute to the patients' global hemostatic function. Our results yield clinically relevant information for the personalised management of patients and eventually precision medicine for fibrinogen disorders.

Biohybrid Nanosystems for Cancer Treatment: Merging the Best of Two Worlds.

During the last 20+ years, research into the biomedical application of nanotechnology has helped in reshaping cancer treatment. The clinical use of several passively targeted nanosystems resulted in improved quality of care for patients. However, the therapeutic efficacy of these systems is not superior to the original drugs. Moreover, despite extensive investigations into actively targeted nanocarriers, numerous barriers still remain before their successful clinical translation, including sufficient bloodstream circulation time and efficient tumor targeting. The combination of synthetic nanomaterials with biological elements (e.g., cells, cell membranes, and macromolecules) is presently the cutting-edge research in cancer nanotechnology. The features provided by the biological moieties render the particles with prolonged bloodstream circulation time and homotopic targeting to the tumor site. Moreover, cancer cell membranes serve as sources of neoantigens, useful in the formulation of nanovaccines. In this chapter, we will discuss the advantages of biohybrid nanosystems in cancer chemotherapy, immunotherapy, and combined therapy, as well as highlight their preparation methods and clinical translatability.

Reactive oxygen species responsive nanoplatforms as smart drug delivery systems for gastrointestinal tract targeting.

The pharmacological therapy for gastrointestinal (GI) diseases, such as inflammatory bowel diseases, continues to present challenges in targeting efficacy. The need for maximal local drug exposure at the inflamed regions of the GI tract has led research to focus on a disease-targeted drug delivery approach. Smart nanomaterials responsive to the reactive oxygen species (ROS) concentrated in the inflamed areas, can be formulated into nanoplatforms to selectively release the active compounds, avoiding unspecific drug delivery to healthy tissues and limiting systemic absorption. Recent developments of ROS-responsive nanoplatforms include combination with other materials to obtain multi-responsive systems and modifications/derivatization to increase the interactions with biological tissues, cell uptake and targeting. This review describes the applications of ROS-responsive nanosystems for on-demand drug delivery to the GI tract.