Dynamic versus static testing and in vivo mechanical performance of poly(glycolide-trimethylene carbonate-ε-caprolactone) delayed release implants.

The manufacturing of millimeter-sized implants for delayed drug release presents several challenges. However, it allows for the encapsulation of a therapeutic agent within a single device, enabling precise control over factors such as geometry, polymer composition, and drug formulation. The relatively large size, however, means that when inserted into subcutaneous tissue the implants experience mechanical stresses that are not predicted by current in vitro methods consisting of incubation under static conditions.

Understanding the Significance of Layer Bonding in Melt Electrowriting.

Melt electrowriting (MEW) is a high-resolution additive manufacturing technology capable of depositing micrometric fibers onto a moving collector to form 3D scaffolds of controlled mechanical properties. While the critical role of layer bonding to achieve mechanical integrity in fused deposition modeling has been widely reported, it remains largely unknown in MEW, in part due to a lack of methods to assess it. Here, a systematic framework is developed to unravel the significance of layer bonding in MEW scaffolds and its ultimate effect on their mechanical properties.

Use of tissue adhesive for neonatal intravenous access devices: A scoping review.

Unlabelled: Neonates often require vascular access devices for medication or fluid therapy, but a third of devices fail before treatment completion or end with a complication. For adults and children, securing these devices with tissue adhesive (TA) increases the dwell and reduces complications. However, there is a lack of evidence for the neonatal population.

Unravelling the physicochemical and antimicrobial mechanisms of human serum albumin/tannic acid coatings for medical-grade polycaprolactone scaffolds.

Biofilm-related biomaterial infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation. To date, a large body of research can be reviewed for coatings which potentially prevent bacterial infection while promoting implant integration. Yet only a very small number has been translated from bench to bedside.

Stability and antigenicity of Chlamydia muridarum major outer membrane protein antigen at body temperature.

Chlamydia is an obligate intracellular bacterial pathogen responsible for disease and infertility across multiple species. Currently vaccines are being studied to help reduce the prevalence of this disease. The main advantage of protein subunit vaccines is their high degree of safety although this is traded off with the requirement for multiple booster doses to achieve complete protection.

pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug.

The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)).

Haemostatic discs demonstrate physical efficacy against microbes commonly associated with central-line-associated bloodstream infections.

Background: Vascular access devices form an essential component in the management of acute and chronic medical conditions. Introduction and ongoing management of these devices are linked with bundles of care aimed at reducing associated risks including bleeding and infection.

Aim: To evaluate the antimicrobial potential of the potassium ferrate haemostatic disc on Gram-positive (Staphylococcus aureus) and Gram-negative (Klebsiella pneumoniae, Pseudomonas aeruginosa) bacteria and on Candida albicans.

Enhanced clearance of C. muridarum infection using azithromycin-loaded liposomes.

Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. There is now emerging evidence of a potential link between Chlamydia and impaired male fertility.

Direct ink writing of multifunctional nanocellulose and allyl-modified gelatin biomaterial inks for the fabrication of mechanically and functionally graded constructs.

Recreating the intricate mechanical and functional gradients found in natural tissues through additive manufacturing poses significant challenges, including the need for precise control over time and space and the availability of versatile biomaterial inks. In this proof-of-concept study, we developed a new biomaterial ink for direct ink writing, allowing the creation of 3D structures with tailorable functional and mechanical gradients. Our ink formulation combined multifunctional cellulose nanofibrils (CNFs), allyl-functionalized gelatin (0.

Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide.

The bactericidal effects of inhalable ciprofloxacin (CIP) loaded-poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) with traces of zinc oxide (ZnO) were investigated against clinical strains of the respiratory pathogens and CIP-loaded PEtOx NPs retained their bactericidal activity within the formulations compared to free CIP drugs against these two pathogens, and bactericidal effects were enhanced with the inclusion of ZnO. PEtOx polymer and ZnO NPs did not show bactericidal activity alone or in combination against these pathogens. The formulations were tested to determine the cytotoxic and proinflammatory effects on airway epithelial cells derived from healthy donors (NHBE), donors with chronic obstructive pulmonary disease (COPD, DHBE), and a cell line derived from adults with cystic fibrosis (CFBE41o-) and macrophages from healthy adult controls (HCs), and those with either COPD or CF.

Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture.

Basement membrane extracts (BME) derived from Engelbreth-Holm-Swarm (EHS) mouse sarcomas such as Matrigel remain the gold standard extracellular matrix (ECM) for three-dimensional (3D) cell culture in cancer research. Yet, BMEs suffer from substantial batch-to-batch variation, ill-defined composition, and lack the ability for physichochemical manipulation. Here, we developed a novel 3D cell culture system based on thiolated gelatin (Gel-SH), an inexpensive and highly controlled raw material capable of forming hydrogels with a high level of biophysical control and cell-instructive bioactivity.

Stability of Inhaled Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticle Dry Powder Inhaler Formulation in High Stressed Conditions.

In this study, the stability of ciprofloxacin (CIP)-loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) was investigated at normal and high stressed conditions. The blank NPs were used to understand the intrinsic physicochemical properties of the polymer NPs under these storage conditions. The formulated NPs were prepared by a coassembly reaction and dried by lyophilization.

Controlled release vaccine implants for delivery of booster immunisations.

Most current animal vaccine regimes involve a primary vaccination followed sometime later by a booster vaccination. This presents challenges when vaccinating difficult to access animals such as livestock. Mustering livestock to deliver a vaccine boost is costly and stressful for animals.

Cell delivery systems: Toward the next generation of cell therapies for type 1 diabetes.

Immunoprotection and oxygen supply are vital in implementing a cell therapy for type 1 diabetes (T1D). Without these features, the transplanted islet cell clusters will be rejected by the host immune system, and necrosis will occur due to hypoxia. The use of anti-rejection drugs can help protect the transplanted cells from the immune system; yet, they also may have severe side effects.

In vivo evaluation of skin integration with ventricular assist device drivelines.

Background: Ventricular assist device (VAD) driveline exit site infection is a common complication. 3D scaffolds manufactured with highly homogeneous pores via melt electro-writing (MEW) may generate an improved skin-driveline interface which permits cellular in-growth and creates a barrier to prevent bacterial migration along the driveline tissue tunnel. This study investigated skin integration on segments of Heartmate 3 driveline: smooth polyurethane, velour, and on a custom MEW scaffold in a small animal model.

Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections.

Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs.

Thermoresponsive Polymer-Antibiotic Conjugates Based on Gradient Copolymers of 2-Oxazoline and 2-Oxazine.

A polymer-antibiotic conjugate with thermoresponsive properties near body temperature is presented. The backbone polymer is a copolymer of 2--propyl-2-oxazine (PropOzi) and methoxycarbonylethyl-2-oxazoline (CMestOx) which is conjugated with the broad-spectrum antibiotic, cefazolin, via modification of the methyl ester group of CMestOx. The resulting polymer-antibiotic conjugate has a cloud point temperature near body temperature, meaning that it can form a homogenous solution if cooled, but when injected into a skin-mimic at 37 °C, it forms a drug depot precipitate.

A Self-Catalyzed Visible Light Driven Thiol Ligation.

We introduce a highly efficient ligation system based on a visible light-induced rearrangement affording a thiophenol which rapidly undergoes thiol-Michael additions. Unlike conventional light-triggered thiol-ene/yne systems, which rely on the use of photocaged bases/nucleophiles, (organo)-photo catalysts, or radical photoinitiators, our system provides a light-induced reaction in the absence of any additives. The ligation is self-catalyzed the pyridine mediated deprotonation of the photochemically generated thiophenol.

Antibacterial Albumin-Tannic Acid Coatings for Scaffold-Guided Breast Reconstruction.

Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms.

Elastic Bioresorbable Polymeric Capsules for Osmosis-Driven Delayed Burst Delivery of Vaccines.

Single-administration vaccine delivery systems are intended to improve the efficiency and efficacy of immunisation programs in both human and veterinary medicine. In this work, an osmotically triggered delayed delivery device was developed that was able to release a payload after a delay of approximately 21 days, in a consistent and reproducible manner. The device was constructed out of a flexible poly(ε-caprolactone) photo-cured network fabricated into a hollow tubular shape, which expelled approximately 10% of its total payload within 2 days after bursting.

Poly(2-allylamidopropyl-2-oxazoline)-Based Hydrogels: From Accelerated Gelation Kinetics to Compatibility in a Murine Subdermal Implant Model.

A rapid photo-curing system based on poly(2-ethyl-2-oxazoline--2-allylamidopropyl-2-oxazoline) and its compatibility are presented. The base polymer was synthesized from the copolymerization of 2-ethyl-2-oxazoline (EtOx) and the methyl ester containing 2-methoxycarboxypropyl-2-oxazoline (CMestOx) followed by amidation with allylamine to yield a highly water-soluble macromer. We showed that spherical hydrogels can be obtained by a simple water-in-oil gelation method using thiol-ene coupling and investigated the biocompatibility of these hydrogel spheres in a 28-day murine subdermal model.

Injectable biocompatible poly(2-oxazoline) hydrogels by strain promoted alkyne-azide cycloaddition.

Poly(2-alkyl-2-oxazoline) (PAOx) hydrogels are tailorable synthetic materials with demonstrated biomedical applications, thanks to their excellent biocompatibility and tunable properties. However, their use as injectable hydrogels is challenging as it requires invasive surgical procedures to insert the formed hydrogel into the body due to their nonsoluble 3D network structures. Herein, we introduce cyclooctyne and azide functional side chains to poly(2-oxazoline) copolymers to induce in situ gelation using strain promoted alkyne-azide cycloaddition.

Prevascularized Retrievable Hybrid Implant to Enhance Function of Subcutaneous Encapsulated Islets.

Replacement of pancreatic β-cells is one of the most promising treatment options for treatment of type 1 diabetes (T1D), even though, toxic immunosuppressive drugs are required. In this study, we aim to deliver allogeneic β-cell therapies without antirejection drugs using a bioengineered hybrid device that contains microencapsulated β-cells inside 3D polycaprolactone (PCL) scaffolds printed using melt electrospin writing (MEW). Mouse β-cell (MIN6) pseudoislets and QS mouse islets are encapsulated in alginate microcapsules, without affecting viability and insulin secretion.