Injectable peptide-glycosaminoglycan hydrogels for soft tissue repair: assessment for nucleus augmentation.

We report the development of peptide-glycosaminoglycan hydrogels as injectable biomaterials for load-bearing soft tissue repair. The hydrogels are injectable as a liquid for clinical delivery, rapidly form a gel , and mimic the osmotic swelling behaviour of natural tissue. We used a new model to demonstrate their application as a nucleus augmentation material for the treatment of intervertebral disc degeneration.

Vesicle-based formulations for pain treatment: a narrative review.

Pain, a complex and debilitating condition, necessitates innovative therapeutic strategies to alleviate suffering and enhance patients' quality of life. Vesicular systems hold the potential to enhance precision of drug localisation and release, prolong the duration of therapeutic action and mitigate adverse events associated with long-term pharmacotherapy. This review critically assesses the current state-of-the-art in vesicle-based formulations (liposomes, polymersomes, ethosomes, and niosomes) for pain management applications.

Topological and Morphological Membrane Dynamics in Giant Lipid Vesicles Driven by Monoolein Cubosomes.

Lipid nanoparticles have important applications as biomedical delivery platforms and broader engineering biology applications in artificial cell technologies. These emerging technologies often require changes in the shape and topology of biological or biomimetic membranes. Here we show that topologically-active lyotropic liquid crystal nanoparticles (LCNPs) can trigger such transformations in the membranes of giant unilamellar vesicles (GUVs).

Development and validation of a mouse model to investigate post surgical pain after laparotomy.

Background: Postoperative pain following abdominal surgery is a significant obstacle to patient recovery, often necessitating high analgesic doses associated with adverse effects like cognitive impairment and cardiorespiratory depression. Reliable animal models are crucial for understanding the pathophysiology of post surgical pain and developing more effective pain-relieving strategies.

Methods: We developed a mouse model to replicate peritoneal trauma induced by abdominal surgery.

Design of oscillatory dynamics in numerical simulations of compartment-based enzyme systems.

Enzymatic reactions that yield non-neutral products are known to involve feedback due to the bell-shaped pH-rate curve of the enzyme. Compartmentalizing the reaction has been shown to lead to transport-driven oscillations in theory; however, there have been few reproducible experimental examples. Our objective was to determine how the conditions could be optimized to achieve pH oscillations.

Unraveling the Phase Behavior, Mechanical Stability, and Protein Reconstitution Properties of Polymer-Lipid Hybrid Vesicles.

Hybrid vesicles consisting of natural phospholipids and synthetic amphiphilic copolymers have shown remarkable material properties and potential for biotechnology, combining the robustness of polymers with the biocompatibility of phospholipid membranes. To predict and optimize the mixing behavior of lipids and copolymers, as well as understand the interaction between the hybrid membrane and macromolecules like membrane proteins, a comprehensive understanding at the molecular level is essential. This can be achieved by a combination of molecular dynamics simulations and experiments.

Controlling the Self-Assembly and Material Properties of β-Sheet Peptide Hydrogels by Modulating Intermolecular Interactions.

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation.

High Resolution Membrane Structures within Hybrid Lipid-Polymer Vesicles Revealed by Combining X-Ray Scattering and Electron Microscopy.

Hybrid vesicles consisting of phospholipids and block-copolymers are increasingly finding applications in science and technology. Herein, small angle X-ray scattering (SAXS) and cryo-electron tomography (cryo-ET) are used to obtain detailed structural information about hybrid vesicles with different ratios of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and poly(1,2-butadiene-block-ethylene oxide) (PBd -PEO , M  = 1800 g mol ). Using single particle analysis (SPA) the authors are able to further interpret the information gained from SAXS and cryo-ET experiments, showing that increasing PBd -PEO mole fraction increases the membrane thickness from 52 Å for a pure lipid system to 97 Å for pure PBd -PEO vesicles.

Dynamics of asymmetric membranes and interleaflet coupling as intermediates in membrane fusion.

Membrane fusion is a tool to increase the complexity of model membrane systems. Here, we use silica nanoparticles to fuse liquid-disordered DOPC giant unilamellar vesicles (GUVs) and liquid-ordered DPPC:cholesterol (7:3) GUVs. After fusion, GUVs display large membrane domains as confirmed by fluorescence confocal microscopy.

Protein corona alters the mechanisms of interaction between silica nanoparticles and lipid vesicles.

The use of nanoparticles (NPs) for biomedical applications implies their delivery into the organism where they encounter biological fluids. In such biological fluids, proteins and other biomolecules adhere to the surface of the NPs forming a biomolecular corona that can alter significantly the behaviour of the nanomaterials. Here, we investigate the impact of a bovine serum albumin corona on interactions between silica nanoparticles (SNPs) of two different sizes and giant lipid vesicles.

Detergent-Free Functionalization of Hybrid Vesicles with Membrane Proteins Using SMALPs.

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis, and synthetic biology. However, functionalization of HVs with membrane proteins remains laborious and expensive, creating a significant current challenge in the field. Here, using a new approach of extraction with styrene-maleic acid (SMA), we show that a membrane protein (cytochrome ) directly transfers into HVs with an efficiency of 73.

Collective Behavior of Urease pH Clocks in Nano- and Microvesicles Controlled by Fast Ammonia Transport.

The transmission of chemical signals via an extracellular solution plays a vital role in collective behavior in cellular biological systems and may be exploited in applications of lipid vesicles such as drug delivery. Here, we investigated chemical communication in synthetic micro- and nanovesicles containing urease in a solution of urea and acid. We combined experiments with simulations to demonstrate that the fast transport of ammonia to the external solution governs the pH-time profile and synchronizes the timing of the pH clock reaction in a heterogeneous population of vesicles.

Membrane mixing and dynamics in hybrid POPC/poly(1,2-butadiene--ethylene oxide) (PBd--PEO) lipid/block co-polymer giant vesicles.

Lipids and block copolymers can individually self-assemble into vesicles, each with their own particular benefits and limitations. Combining polymers with lipids allows for further optimisation of the vesicle membranes for bionanotechnology applications. Here, POPC lipid is mixed with poly(1,2-butadiene--ethylene oxide) of two different molecular weights (PBd-PEO, Mr = 1800 g mol and PBd-PEO, Mr = 1150 g mol) in order to investigate how increasing the polymer fraction affects membrane mixing, hydration and fluidity.

Evaluation of injectable nucleus augmentation materials for the treatment of intervertebral disc degeneration.

Back pain affects a person's health and mobility as well as being associated with large health and social costs. Lower back pain is frequently caused by degeneration of the intervertebral disc. Current operative and non-operative treatments are often ineffective and expensive.

Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles.

Fusion events in living cells are intricate phenomena that require the coordinate action of multicomponent protein complexes. However, simpler synthetic tools to control membrane fusion in artificial cells are highly desirable. Native membrane fusion machinery mediates fusion, driving a delicate balance of membrane curvature and tension between two closely apposed membranes.

Breaking Isolation to Form New Networks: pH-Triggered Changes in Connectivity inside Lipid Nanoparticles.

There is a growing demand to develop smart nanomaterials that are structure-responsive as they have the potential to offer enhanced dose, temporal and spatial control of compounds and chemical processes. The naturally occurring pH gradients found throughout the body make pH an attractive stimulus for guiding the response of a nanocarrier to specific locations or (sub)cellular compartments in the body. Here we have engineered highly sensitive lyotropic liquid crystalline nanoparticles that reversibly respond to changes in pH by altering the connectivity within their structure at physiological temperatures.

The influence of phosphatidylserine localisation and lipid phase on membrane remodelling by the ESCRT-II/ESCRT-III complex.

The endosomal sorting complex required for transport (ESCRT) organises in supramolecular structures on the surface of lipid bilayers to drive membrane invagination and scission of intraluminal vesicles (ILVs), a process also controlled by membrane mechanics. However, ESCRT association with the membrane is also mediated by electrostatic interactions with anionic phospholipids. Phospholipid distribution within natural biomembranes is inhomogeneous due to, for example, the formation of lipid rafts and curvature-driven lipid sorting.

Cryo-EM structures of an insecticidal Bt toxin reveal its mechanism of action on the membrane.

Insect pests are a major cause of crop losses worldwide, with an estimated economic cost of $470 billion annually. Biotechnological tools have been introduced to control such insects without the need for chemical pesticides; for instance, the development of transgenic plants harbouring genes encoding insecticidal proteins. The Vip3 (vegetative insecticidal protein 3) family proteins from Bacillus thuringiensis convey toxicity to species within the Lepidoptera, and have wide potential applications in commercial agriculture.

Hydrodynamic Mixing Tunes the Stiffness of Proteoglycan-Mimicking Physical Hydrogels.

Self-assembling hydrogels are promising materials for regenerative medicine and tissue engineering. However, designing hydrogels that replicate the 3-4 order of magnitude variation in soft tissue mechanics remains a major challenge. Here hybrid hydrogels are investigated formed from short self-assembling β-fibril peptides, and the glycosaminoglycan chondroitin sulfate (CS), chosen to replicate physical aspects of proteoglycans, specifically natural aggrecan, which provides structural mechanics to soft tissues.

Tuning stable noble metal nanoparticles dispersions to moderate their interaction with model membranes.

Hypothesis: The properties of stable gold (Au) nanoparticle dispersions can be tuned to alter their activity towards biomembrane models.

Experiments: Au nanoparticle coating techniques together with rapid electrochemical screens of a phospholipid layer on fabricated mercury (Hg) on platinum (Pt) electrode have been used to moderate the phospholipid layer activity of Au nanoparticle dispersions. Screening results for Au nanoparticle dispersions were intercalibrated with phospholipid large unilamellar vesicle (LUV) interactions using a carboxyfluorescein (CF) leakage assay.

Characterisation of Hybrid Polymersome Vesicles Containing the Efflux Pumps NaAtm1 or P-Glycoprotein.

Investigative systems for purified membrane transporters are almost exclusively reliant on the use of phospholipid vesicles or liposomes. Liposomes provide an environment to support protein function; however, they also have numerous drawbacks and should not be considered as a "one-size fits all" system. The use of artificial vesicles comprising block co-polymers (polymersomes) offers considerable advantages in terms of structural stability; provision of sufficient lateral pressure; and low passive permeability, which is a particular issue for transport assays using hydrophobic compounds.

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations.

Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene--poly(ethylene oxide) polymers (PBd-PEO and PBd-PEO) mixed with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions.

Biodegradable hybrid block copolymer - lipid vesicles as potential drug delivery systems.

The anticipated benefits of nano-formulations for drug delivery are well known: for nanomedicines to achieve this potential, new materials are required with predictive and tuneable properties. Excretion of excipients following delivery is advantageous to minimise the possibility of adverse effects; biodegradability to non-toxic products is therefore desirable. With this in mind, we aim to develop tuneable hybrid lipid-block copolymer vesicle formulations where the hydrophilic polymer block is polyethylene glycol (PEG), which has accepted biocompatibility, and the hydrophobic block of the polymer is biodegradable: polycaprolactone (PCL) or polylactide (PLA).

Mechanomodulation of Lipid Membranes by Weakly Aggregating Silver Nanoparticles.

Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore, understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute effects, it is desirable to understand more subtle interactions that could lead to milder, chronic health impacts.

In Vitro Membrane Remodeling by ESCRT is Regulated by Negative Feedback from Membrane Tension.

Artificial cells can shed new light on the molecular basis for life and hold potential for new chemical technologies. Inspired by how nature dynamically regulates its membrane compartments, we aim to repurpose the endosomal sorting complex required for transport (ESCRT) to generate complex membrane architectures as suitable scaffolds for artificial cells. Purified ESCRT-III components perform topological transformations on giant unilamellar vesicles to create complex "vesicles-within-a-vesicle" architectures resembling the compartmentalization in eukaryotic cells.